Abstracts of 2nd Phd Research Symposium in Health Sciences and Biomedicine Part 1

e00001
LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease

Maria P. Ikonomopoulou1,2,3,8,*, Yaiza Lopez-Mancheño4, Marta G. Novelle4, Maite Martinez-Uña4, Lahiru Gangoda6,7, Martin Pal6,7, Luis Filipe Costa-Machado5, Pablo Jose Fernandez-Marcos5, Grant A. Ramm1,2, and Manuel Alejandro Fernandez-Rojo1,2,4,8,9,*.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00001

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Maria P. Ikonomopoulou, Yaiza Lopez-Mancheño, Marta G. Novelle, Maite Martinez-Uña, Lahiru Gangoda, Martin Pal, Luis Filipe Costa-Machado, Pablo Jose Fernandez-Marcos, Grant A. Ramm and Manuel Alejandro Fernandez-Rojo. et al. LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease.. IBJ Plus 2021 (S4) e0001:10.24217/2531-0151.21v1s4.00001

Edited: Madrid, España.

Abstract

Introduction: Devil facial tumor disease (DFTD) and its lack of available therapies are propelling the Tasmanian devil population toward extinction. Only recently, the immunomodulatory molecule imiquimod and the gomesin spider peptide have been shown to display apoptotic activity against DFTD cells and with minimum cytotoxicity on healthy devil fibroblasts (FIBs). Most molecular mechanisms that drive the proliferation of DFTD cells remain obscure.

Material and Methods: The evaluation of the molecular mechanisms that unravel the persistence of DFTD has been driven using a variety of techniques. Including cell proliferation assays, gene expression, apoptosis and cell cycle analysis by Fluorescence-Activated Cell Sorting (FACS), metabolic flux analysis by Seahorse technology, Western Blotting and xenograph tumor models of DFTD.

Results: This study demonstrates that cholesterol homeostasis and carbohydrate energy metabolism sustain the proliferation of DFTD cells in a cell-type-dependent manner. In addition, we show that the liver-X nuclear receptor-b (LXRb), a major cholesterol cellular sensor, and its natural ligand 24S-hydroxycholesterol promote the proliferation of DFTD cells via a metabolic switch toward aerobic glycolysis. As a proof of concept of the role of cholesterol homeostasis on DFTD proliferation, we show that atorvastatin, an FDA-approved statin-drug subtype used against human cardiovascular diseases that inhibits cholesterol synthesis, shuts down DFTD energy metabolism and prevents tumor growth in an in vivo DFTD-xenograft model.

Conclusions: In conclusion, we show that intervention against cholesterol homeostasis and carbohydrate-dependent energy metabolism by atorvastatin constitutes a feasible biochemical treatment against DFTD, which may assist in the conservation of the Tasmanian devil.

e00002
Investigating the role of directional and fluctuating asymmetry in the developmental instability of patients with idiopathic scoliosis

José María González-Ruiz 1, Aroa Casado 2, María Isabel Pérez-Núñez 3, Mª Dolores García-Alfaro 3, Markus Bastir 1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00002

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: José María González-Ruiz, Aroa Casado , María Isabel Pérez-Núñez , Mª Dolores García-Alfaro , Markus Bastir , et al. Investigating the role of directional and fluctuating asymmetry in the developmental instability of patients with idiopathic scoliosis. IBJ Plus 2021 (S4)e0002:10.24217/2531-0151.21v1s4.00002

Edited: Madrid, España.

Abstract

Introduction: Short-term fasting is a nutritional intervention that has been previously evaluated in healthy
volunteers, cancer patients and cancer animal models with promising results. Recent studies in humans show
a better prognostic in cancer patients that fasted during chemotherapy. In accordance with these results, other
studies with cancer mouse models have observed that fasting reduced tumor size and delayed tumor progression
after chemotherapy administration. This effect is parallel with promoting a more potent immune response.

Material and Methods: B16F10 tumor-bearing immunocompetent p21 wild-type (p21 WT) and p21 knock-out
(p21 KO) C56BL/6OlaHsd male and female mice were injected intraperitoneally with 10 mg/kg doxorubicin
when the tumor reached a certain size, and either followed short-term fasting (24 hours before and 24 hours
after chemotherapy) or fed normally (chemotherapy group). A control group not treated with doxorubicin and
fed normally was also included. Tumor, inguinal lymph nodes and blood samples were obtained 7 days after
chemotherapy administration and analyzed by multi-parametric flow cytometry.

Results: Short-term fasting (48h) in combination with one cycle of 10 mg/kg of the chemotherapeutic agent
doxorubicin was effective in reducing melanoma B16F10 tumor size 7 days after chemotherapy administration
in p21 WT and p21 KO male, but not in female mice. In accordance to the diminished tumor progression, shortterm
fasting promoted two critical changes in several immune populations. First, a decrease in tumor-promoting
immune cells: in tumors from male mice, short-term fasting reduced total tumor-associated macrophages
(TAMs), M2-polarized macrophages, the transition from M1 to M2 macrophages, neutrophilic myeloid-derived
suppressor cells (MDSCs) and regulatory T cells; in blood from female mice, fasting lessened T helper type 2 (Th2)
cells. Second, fasting promoted an increase in effector immune populations: in lymph nodes from male mice,
fasting raised Natural Killer T (NKT) cells; in tumors from male mice, fasting expanded effector NKT cells, cytotoxic
T lymphocytes (CTLs), effector T helper cells and plasmacytoid dendritic cells. These populations in females were
not altered.

Conclusions: These data indicate that 48h fasting in combination with doxorubicin administration is effective in
reducing B16F10 tumor size in male, but not female mice. Also, immune profiling shows a clearer view of the
anti-tumor immune response elicited by short-term fasting in different tissues, a beneficial effect that is stronger
in male mice. In addition, our genetic model of p21 KO mice indicates that p21 is not critical in the beneficial
effects of fasting to reduce B16F10 tumor progression.

e00004
Sex-dependent and p21-independent enhancement of chemotherapy efficacy by short-term fasting.

Andrés Pastor-Fernández1, Adrián Plaza1, Cristina Pantoja1, Lola Martínez2, José Luis López-Aceituno1, Arantzazu Sierra-Ramirez1, Marta Barradas1, Ildefonso Rodriguez-Ramiro1, Pablo Jose Fernandez-Marcos1,*.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00004

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Andrés Pastor-Fernández, Adrián Plaza, Cristina Pantoja, Lola Martínez, José Luis López-Aceituno, Arantzazu Sierra-
Ramirez, Marta Barradas, Ildefonso Rodriguez-Ramiro, Pablo Jose Fernandez-Marcos, et al. Sex-dependent and p21-independent
enhancement of chemotherapy efficacy by short-term fasting.IBJ Plus 2021 (S4)e0004:10.24217/2531-0151.21v1s4.00004

Edited: Madrid, España.

Abstract

Introduction: Short-term fasting is a nutritional intervention that has been previously evaluated in healthy volunteers, cancer patients and cancer animal models with promising results. Recent studies in humans show a better prognostic in cancer patients that fasted during chemotherapy. In accordance with these results, other studies with cancer mouse models have observed that fasting reduced tumor size and delayed tumor progression after chemotherapy administration. This effect is parallel with promoting a more potent immune response.

Material and Methods: B16F10 tumor-bearing immunocompetent p21 wild-type (p21 WT) and p21 knock-out (p21 KO) C56BL/6OlaHsd male and female mice were injected intraperitoneally with 10 mg/kg doxorubicin when the tumor reached a certain size, and either followed short-term fasting (24 hours before and 24 hours after chemotherapy) or fed normally (chemotherapy group). A control group not treated with doxorubicin and fed normally was also included. Tumor, inguinal lymph nodes and blood samples were obtained 7 days after chemotherapy administration and analyzed by multi-parametric flow cytometry.

Results: Short-term fasting (48h) in combination with one cycle of 10 mg/kg of the chemotherapeutic agent doxorubicin was effective in reducing melanoma B16F10 tumor size 7 days after chemotherapy administration in p21 WT and p21 KO male, but not in female mice. In accordance to the diminished tumor progression, shortterm fasting promoted two critical changes in several immune populations. First, a decrease in tumor-promoting immune cells: in tumors from male mice, short-term fasting reduced total tumor-associated macrophages (TAMs), M2-polarized macrophages, the transition from M1 to M2 macrophages, neutrophilic myeloid-derived suppressor cells (MDSCs) and regulatory T cells; in blood from female mice, fasting lessened T helper type 2 (Th2) cells. Second, fasting promoted an increase in effector immune populations: in lymph nodes from male mice, fasting raised Natural Killer T (NKT) cells; in tumors from male mice, fasting expanded effector NKT cells, cytotoxic T lymphocytes (CTLs), effector T helper cells and plasmacytoid dendritic cells. These populations in females were not altered.

Conclusions: These data indicate that 48h fasting in combination with doxorubicin administration is effective in reducing B16F10 tumor size in male, but not female mice. Also, immune profiling shows a clearer view of the anti-tumor immune response elicited by short-term fasting in different tissues, a beneficial effect that is stronger in male mice. In addition, our genetic model of p21 KO mice indicates that p21 is not critical in the beneficial effects of fasting to reduce B16F10 tumor progression.

e00005
Psixport: mobile app for ecological momentary assessment of psychological dimensions in sport injury.

Luis J. González1, Víctor Rubio Franco2, José Manuel Hernández3, Iván Sánchez 4..

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00005

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Luis J. González, Víctor Rubio Franco, José Manuel Hernández, Iván Sánchez, et al. Psixport: mobile app for ecological
momentary assessment of psychological dimensions in sport injury. IBJ Plus 2021 (S4)e0005:10.24217/2531-0151.21v1s4.00005

Edited: Madrid, España.

Abstract

Introduction: Psychological variables such as feelings, thoughts or emotions had been usually assessed via one-time retrospective self-reports, but these methods had shown serious limitations to gather accurate information about these variables due to their changing and dynamic nature. The Ecological Momentary Assessment (EMA) approach provides a method that copes with some of the limitations that retrospective methods present gathering real-time information about changing and dynamic variables such as feelings, thoughts, or behaviours. In the Sport injury rehabilitation field, injured athletes’ psychological responses during their rehabilitation process such as pain perceptions, cognitive, emotional, and behavioural responses, change over time and can influence the rehabilitation outcomes. Taking these responses changes into account could help therapists to adapt each rehabilitation process and increase their effectiveness. With this purpose, PSIXPORT®, an EMA mobile app was designed to gather accurate real-time information about Anterior Cruciate Ligament (ACL) torn injured athletes’ cognitive appraisals, emotional responses, behavioural responses, and pain perceptions during their rehabilitation processes. This study pursued three main goals: to test PSIXPORT ability to gather real time information about injured athletes` thoughts, feelings, and behaviours during their rehabilitation processes; to compare the reliability and differences between PSIXPORT real- time data gathered and one-time retrospective self-report data; and to test PSIXPORT perceived usability from users.

Materials and Methods: 28 ACL injured athletes (10 men and 18 women) were assessed during their rehabilitation process with PSIXPORT® (Athletes completed 15 or more PSIXPORT’s daily assessments), completed a retrospective questionnaire, and the uMARS test.

Results: Results confirmed that PSIXPORT is a good tool for gathering real-time information about injured athletes’ psychological responses during the rehabilitation process. Data gathered with PSIXPORT showed to be more accurate than one-time retrospective self-reports’ information.

Conclusions: Repeated measures over time are necessary to accurately assess changing and dynamic variables such feelings, thoughts, or emotions. PSIXPORT, a mobile app based on an EMA approach, has shown to be a useful tool to gather accurate information about these variables’ changes.

e00006
Automatic synapse parameter exploration for the interaction of living neurons and models.

Manuel Reyes-Sanchez1, Rodrigo Amaducci1, Irene Elices1,2, Francisco B. Rodriguez 1, Pablo Varona 1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00006

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Manuel Reyes-Sanchez, Rodrigo Amaducci, Irene Elices, Francisco B. Rodriguez, Pablo Varona, et al. Automatic synapse parameter exploration for the interaction of living neurons and models. IBJ Plus 2021 (S4)e0006:10.24217/25310151.21v1s4.00006.

Edited: Madrid, España.

Abstract

Hybrid circuits that connect living and model neurons are key tools to study neural dynamics and to assess the role of specific neuron and network properties in emergent phenomena of neural computation. In this work, we deal with the automatic adaptation and mapping of parameters in hybrid circuits and, in particular, those that yield dynamical invariants. Such invariants take the form of robust relationships between the intervals that build robust sequences arising from such interaction. We first automated the adaptation of model neurons to work in same amplitude regime and time scale of living neurons. Then, we automatically explored and mapped the synapse parameter space that led to archive a specific dynamical invariant target. Our approach uses multiple configurations and parallel computing from the same input series of living neurons to build the mappings. We illustrate this methodology in the study of dynamical invariants that build robust sequences in neural rhythms. The existence of such invariants has been recently unveiled in the pyloric CPG of crustacean, even under the presence of intrinsic or induced large variability in the rhythms.

Hybrid circuits are composed of living and model neurons and have a long tradition (e.g., see Le Masson et al. 2002, Amaducci et al, 2019). In the proposed protocol, we input biological series with a characteristic temporal structure of spiking-bursting dynamics to different model neurons. The biological recordings are preprocessed to automatically adapt the corresponding time and amplitude scales to those of the synapse and neuron models employed. Our methodology can then map the neuron and synapse parameters that yield a predefined dynamical invariant taking into account the temporal structure of the model output (Reyes-Sanchez et al. 2020). This approach allows a full characterization of the parameter space that contributes to the generation of the predefined target dynamics.

To illustrate this protocol that combines experimental recordings and theoretical paradigms, we applied it to the search for dynamical invariants established between a living pyloric CPG cell and a model neuron (Komendantov & Kononenko 1996) connected through a graded synapse model. Dynamical invariants are preserved cycle-by cycle, even during transients (Elices et al. 2019). We have mapped the presence of a linear relationship, i.e., an invariant, between the interval defined by the beginning of the bursting activity of the two neurons (first-to-first spike interval between the living and model neurons) and the instantaneous period of their sequence in such hybrid circuit. The proposed strategy can be generalized for any hybrid circuit.

e00007
Identifies Polyps in Real Time With Accuracy 96.67% in Screening Colonoscopy Using Convolutional Neural Networks(CNN).

Manuel Reyes-Sanchez1, Rodrigo Amaducci1, Irene Elices1,2, Francisco B. Rodriguez 1, Pablo Varona 1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00007

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Hadi Abooei Mehrizi, et al. Identifies Polyps in Real Time With Accuracy 96.67% in Screening Colonoscopy Using Convolutional Neural Networks(CNN). IBJ Plus 2021 (S4)e0007:10.24217/2531-0151.21v1s4.00007.

Edited: Madrid, España.

Abstract

Introduction: Colorectal cancer(CRC) is the third most common cancer in the world and is the second in terms of mortality, with more than 862,000 kills just in 2018 according to the World Health Organization(WHO) report. (https://www.who.int/news-room/factsheets/detail/cancer). There are several methods to diagnose CRC and reduce it’s mortality rate, but the most golden method is colonoscopy screening. The purpose of` this method is to increase the Adenoma detection rate(ADR). The importance of increasing ADR is that due to international standards, colonoscopy is repeated for a person at intervals of three to ten years, and this will be enough time for the patient to get CRC. The benefits of this method is when we have the highest ADR. On the other hand, several factors are effective in reducing ADR in normal colonoscopy, such as weakness of the screening device, medical mistake and the patient’s unpreparedness. It is estimated that every 1% increase in ADR reduces 3% to 6% of CRC. This study tries to find polyps to increase ADR with computer deep learning with neural networks. In this study, we used a Convolutional Neural Network(CNN) for this purpose.

Material and Methods: We designed a simple convolutional neural network(CNN) then we improved it with different methods such as image processing and transfer learning. Then we trained CNN with 1982 unique tagged images extracted from 16 colonoscopic films of more than 10 patients, which resulted in the 96.97% polyps detection. Finally, we will ask an expert colonoscopist to review 5 unlabeled colonoscopic films, and the results were reviewed with and without model asistant.

Results: The optimized CNN identified manually labeled polyps with 96.97 Evaluation of false positive rate and also evaluation of polyp diagnosis results, with and without CNN help. Conclusion: Our model was able to successfully identify 96.97% of the 1982 images including 641 polyps. Also, Due to the simplicity of the model, it can be easily implemented in any clinic which leads to increasing ADR and preventing CRC, but requires validation in large multicenter trials.

e00008
Barriers and facilitators for exclusive breastfeeding of Health System and policies according to Primary Care midwives in Tenerife (Canary Islands, Spain).

Seila Llorente-Pulido 1, *, Estefanía Custodio 2, , M. Rosario López-Giménez 3, Belén Sanz-Barbero 4,5 and Laura Otero-García 5,6 *.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00008

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Seila Llorente-Pulido, Estefanía Custodio, M. Rosario López-Giménez, Belén Sanz-Barbero and Laura Otero-García , et al.
Barriers and facilitators for exclusive breastfeeding of Health System and policies according to Primary Care midwives in Tenerife
(Canary Islands, Spain). IBJ Plus 2021 (S4)e0008:10.24217/2531-0151.21v1s4.00008.

Edited: Madrid, España.

Abstract

In Spain, exclusive breast feeding (EBF) rates are 66%, 53% and 28% at 6 weeks, 3 months and 6 months, respectively,
far below the World Health Organization recommended target of 50% of EBF for at least 6 months. There is
scientific evidence showing the different factors that affect EBF. Primary care (PC) midwives are considered key in
promoting EBF due to their specific competencies. The aim of our study is to shed light on the factors related to the
Healthcare system and health, labour and social policies that facilitate or are detrimental to EBF from the perspective
of PC midwives in Tenerife (Canary Islands, Spain).

The study is based on qualitative methodology. Semi-structured interviews were carried with 20 out of the 53 PC
midwives in staff. We recruited PC midwives using a convenience snowball sampling technique designed to include
a pre-defined set of midwives´ profiles. The in-depth interviews were transcribed using a content analysis approach.
To facilitate the coding process, we used the programme Open Code 3.6. Transcriptions were coded following an
inductive approach that creates emerging codes that summarize the content of each sentence in a paragraph. After,
codes were categorized according to whether they were, in general, “facilitators” or “barriers” of EBF, to later identify
them in a chronological order by subcategories.

PC midwives perceive different factors as facilitators and barriers to EBF. Within the healthcare system, midwives
have identified as barriers the hospital practices that do not allow an early contact and start of EBF, the indiscriminate
use of teats, the lack of support from healthcare professionals, as well as recommendations or suggestions that
lack scientific evidence. Regarding facilitators for EBF, midwives highlight the hospital practices that allow “skin-toskin”,
support from healthcare professionals, and harmonisation of criteria when offering recommendations. Midwives
consider that attending the prenatal courses and breastfeeding workshops directed at women and their families
is very important. On the other hand, regarding policies, midwives point out as barriers the lack of investment in
EBF, the early return to work and the lack of support at work to continue EBF. Midwives also highlight the lack of
publicity around EBF from a real and contemporary perspective.

The results from our research allow us to conclude that healthcare professionals should promote and support EBF. In
order to do this, it is necessary that they receive updated and continuous training within multidisciplinary teams. On
the other hand, it is important to develop adequate health, labour and publicity policies that favour and protect EBF,
as well as maternity/paternity.

e00009
Aging, chronicity, and stigma on methadone treatments.

Sonsoles Gutiérrez-Cáceres*1, Pilar Serrano-Gallardo**, Azucena Pedraz-Marcos**.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00009

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Gutiérrez-Cáceres, S. et al. Aging, chronicity, and stigma on methadone treatments.IBJ Plus 2021 (S4)e0009:10.24217/2531-
0151.21v1s4.00009.

Edited: Madrid, España.

Abstract

Thanks to the effectiveness of methadone treatment, introduced in our country at the early 90s, people who
takes it have overcome the barrier of 50 years. It is a prematurely aged population due to their life history, with
multiple chronic pathologies, with different needs due to their socioeconomic position and with a great stigma
due to the association between methadone and drugs.
Objectives: To know the sociodemographic and clinical profile of people in treatment with methadone and to
explore their experiences in relation to chronicity and future needs, with a gender perspective.

A mixed-method sequential investigation was carried out in two phases. 1- quantitative. Descriptive cross-sectional
study of people under methadone treatment in Madrid Salud centers, through their clinical records. Descriptive
statistics indices and bivariate analysis, total and disaggregated by sex were used. 2- qualitative. Semi-structured
interviews were conducted to analyze the discourses of people >50 years, who have been on methadone
10 years or more.

We found an aging population (N 1488), 65.52% had 50 years or more, men were older (67.07% vs 60.18% p
0.020), with a high number of chronic pathologies, being women who had more risk with a statistical significance:
HIV (36.23% vs 26.86% p 0.001); others that have appeared with age: hypertension, diabetes, lung diseases
or different cancers (61.08% vs 52.86% p 0.008), as well as mental illnesses (46.41% vs 36.40% p 0.001). Likewise,
they do not feel like normal people, but continually judged and distrustful, even by healthcare workers: H59 – “…
because not everyone trusts drug addicts […] it is difficult for them to accept you, for them to see you well…”,
because they are taking a stigmatized medication that are perpetually related to drugs. This leads them to feel
ashamed, so they hide the methadone treatment, making it difficult for them to relate to the rest of the people
who do not take it M56- “In my work I do not say that I take methadone, obviously, it can be a medication, but
it is not an aspirin or paracetamol”. Also, the administration form (tablets or dilution) prevents them from doing
things, such as traveling outside their city, since they cannot pick it up like any other chronic medication in a
pharmacy.

Therefore, it will be necessary to begin to assess the needs of this aging population, favoring adequate resources
for them. The stigma of this medication that has become chronic must be fought, making it equal to any other
chronic treatment.

e00010
Creation of an animal model of arteriovenous fistula and evaluation of the drug eluting balloon in stenosis.

Cristian Arriagada Godoy1, Teresa Fontecilla Echeveste2, Sandra Osorio Véliz3, Santiago Méndez Alonso4, María José Pérez5, Gil Rodríguez Caravaca6.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00010

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Cristian Arriagada Godoy, Teresa Fontecilla Echeveste, Sandra Osorio Véliz, Santiago Méndez Alonso, María José Pérez, Gil Rodríguez Caravaca, et al. Creation of an animal model of arteriovenous fistula and evaluation of the drug eluting balloon in stenosis.. IBJ Plus 2021 (S4)e0010:10.24217/2531-0151.21v1s4.00010

Edited: Madrid, España.

Abstract

Introduction: The global incidence of chronic kidney disease in Spain is 142 / million, 89% of patients start hemodialysis and 79% will use arteriovenous fistulas (AVF). AVF stenosis ranges from 10 – 30%, some groups can reach 50% (diabetic patients, the elderly and women).

Objectives: Revalidate an AVF animal model and evaluate the biological effects of the drug balloon on stenosis. Material and method: Experimental study without randomization in 2 phases. Phase 1: Validation of the porcine animal AVF model. 3-month-old female individuals were included. Performing 2 AVFs per individual at the femoral level, lateral-lateral anastomosis technique. Ultrasound control to determine the caliber, flow and time of stenosis (4 AVFs). Phase 2: Once AVF maturation was achieved and stenosis produced, angioplasty (PTA) was performed with a medicated balloon in an AVF and a simple balloon in a contralateral AVF. Follow-up 3 weeks with ultrasound, euthanizing a month, with sampling for histology (12 AVF)

Results: First Phase: Validation of the animal AVF model. Establishing maturation time, flow measurement and caliber. Non-significant correlation (Pearson = 0.616) (p = 0.107). Second Phase: Histological study showed less intimal thickening in the PTA group with drugs, statistically not significant.

Conclusions: 1. Creation of an AVF animal model with close ultrasound follow-up is feasible and reproducible to determine stenosis and prevent thrombosis of AVF. 2. The use of the drug eluting balloon does not show significant histomorphometric differences in the treatment of AVF stenosis compared to non-drug balloon, but it shows a tendency to explore with longer follow-up

e00011
End-of-life care for pediatric patients with CNS cancer: description and comparison based on palliative care provision.

Íñigo de Noriega1, Raquel Jiménez2, Álvaro Lassaletta3, Ricardo Martino4, Blanca Herrero3.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00011

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Íñigo de Noriega, Raquel Jiménez, Álvaro Lassaletta, Ricardo Martino, Blanca Herrero, et al. End-of-life care for pediatric patients with CNS cancer: description and comparison based on palliative care provision. IIBJ Plus 2021 (S4)e0011:10.24217/25310151.21v1s4.00011.

Edited: Madrid, España.

Abstract

INTRODUCTION: Pediatric CNS cancer constitutes a major cause of morbidity and mortality. Pediatric palliative care (PPC) aims to improve the patient’s quality of life and overall care specially in the end-of-life period. Little data regarding the impact of implementing PPC units (PPCU) in Spain is known. We summarize the comparison of data regarding last month of life care in patients with CNS cancer that were attended or not by a PPCU over 10 years.

MATERIAL & METHODS: Descriptive retrospective analysis of clinical records of deceased patients with a CNS cancer between 1/1/2010-12/31/2020 in H. Niño Jesús. Data was sub-analyzed from a PhD project which aims to describe the characteristics of cancer patients attended by the PPCU of Madrid and the overall care (medical, psychological and social) provided by this Unit and describe the differential attention compared to patients that did not receive PPC interventions. Variables analyzed included epidemiological characteristics, oncological evolution, support measures, oncological treatment and hospital admission days in the last month of life and place of death. Classic tests of hypothesis (non-parametrical or parametrical when applicable) were performed with a stablished significance of 0.05.

RESULTS: 48 patients with a CNS cancer died in the period of study, 36 (75%) attended by the PPCU. No significant differences were found regarding sex, age at diagnosis or at death when grouped based on if they were attended by the PPCU, as well as in total lines of treatment, metastatic diseases at the diagnoses or in the evolution or total ICU admissions. Regarding the last month of care, no differences were found in the administration of chemo or radiotherapy, red blood or platelet transfusions or invasive interventions. However, patients attended by the PPCU stayed less days in hospital in the last month (median of 2 vs 9.5; p=0.02) and last week (median of 0.5 vs 7; p<0.01) and were more prone to die at home (50% vs 0%; p<0.01).

CONCLUSSIONS: The implementation of a PPCU in HIU Niño Jesús, has helped to attended 75% of the deceased patients with a CNS cancer in this institution. Weather the patients were attended or not by the PPCU does not seem to be influenced by their epidemiological or oncological characteristics. The overall oncological and support care does not seem to differ amongst patients based on the intervention of the PPCU, but patients attended by the PPCU spent more days and were more prone to die at their home. Further data on other cancers and specific interventions of the PPCU are currently being analyzed as part of a PhD project in order to find barriers to PPC and to clarify the potential benefits that it can bring to patients.

e00012
A qualitative study into professionals’ experiences with mechanical restraints in Psychiatry: a phenomenological study using focus groups on mental health staff in training.

Luis Nocete Navarro1,2, Beatriz Orgaz Álvarez3, Almudena Medrano Andrés4, María Fe Bravo Ortiz2,3, Alberto Fernández Liria.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00012

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Authors Luis Nocete Navarro, Beatriz Orgaz Álvarez, Almudena Medrano Andrés, María Fe Bravo Ortiz, Alberto Fernández Liria, et al. A qualitative study into professionals’ experiences with mechanical restraints in Psychiatry: a phenomenological study using focus groups on mental health staff in training. IBJ Plus 2021 (S4)e0012:10.24217/2531-0151.21v1s4.00012.

Edited: Madrid, España.

Abstract

Introduction

Mechanical restraint is a coercive measure used for behavioural control in Psychiatry. Despite the fact this procedure is allowed and widely used in Spain, it is not actually regulated by Spanish law.”. Several studies maintain that non-clinical factors (such as professionals’ experiences and the influences of the context) may play a more important role in the use of these measures, than the purely clinical factors attributable to the individual characteristics of patients.

Objectives

The aim of the present research is to understand, from a phenomenological/hermeneutic perspective, the experiences, emotions, attitudes etc. of professionals in training (nursing, clinical psychology and psychiatry), with regards to the use of mechanical restraint within the public mental health network of the Comunidad de Madrid.

Methods

A qualitative phenomenological research methodology was used, involving the development of three different focus groups of professionals in training. The interviews were recorded in audio and video, and the data collected was later transcribed for discussion and thematic analysis.

Results

What we present is the first part of the descriptive findings related to our first research question: How do mental health professionals describe their own experience with the use of mechanical restraints? The results observed so far suggest that these measures generate emotional distress and leads professionals to conflict with their role as caregivers, resulting in the development of different strategies to cope with this situation.We are currently working on the second research question. Based on Grounded Theory, this research will provide a conceptual model that will allow us to understand the meanings underlying professionals’ subjective experiences of using mechanical restraints.

Conclusions

Current descriptive analysis suggests that the results are similar to those observed in the literature and reveals both professional suffering and ethical, emotional, cognitive, and behavioural contradictions in common clinical practice.

e00013
An evaluation of perinatal outcomes in women with low- and medium-risk pregnancies: Towards understanding the organization of intrapartum care in Spain.

Anna Martin-Arribas1,2*, Ramon Escuriet2,3, Rafael Vila-Candel4,5, Cristina González-Blázquez6..

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00013

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Anna Martin-Arribas, Ramon Escuriet, Rafael Vila-Candel, Cristina González-Blázquez, et al. An evaluation of perinatal outcomes in women with low- and medium-risk pregnancies: Towards understanding the organization of intrapartum care in Spain. IBJ Plus 2021 (S4)e0013:10.24217/2531-0151.21v1s4.00013

Edited: Madrid, España.

Abstract

Background: There is considerable evidence that demonstrates a relationship between how care is provided and the perinatal health outcomes. In Spain, most women give birth in highly technological obstetric units staffed by both obstetricians and midwives. The aim of this study was to examine the association between the organization of care and the maternal and neonatal outcomes in women with low- and medium-risk pregnancies in Spain.

Methods: This PhD includes two phases. Firstly, there is a prospective, multicenter, cross-sectional study that was carried out at 44 public hospitals in Spain in the years 2016-2019. The sample size of this study was 11,537 women. The primary outcome was mode of birth. The secondary outcomes included augmentation with oxytocin, use of epidural analgesia, women’s position at birth, perineal integrity, maternal and neonatal admission to intensive care, Apgar score, neonatal resuscitation and early initiation of breastfeeding. Then, a sub analysis was performed with transfer of care as the primary outcome. The secondary outcomes were those included in the first analysis. Univariate and multivariate logistic regression with odds ratio with intervals of confidence at 95% were also calculated. The second phase was a descriptive qualitative study. Three focus groups were performed. Feedback from data were analysed using thematic analysis. Investigator triangulation was used during the analysis.

Results: Midwifery care was associated with lower rates of dystocic births and severe perineal damage and had no higher adverse outcomes in comparison with obstetric care. No statistically significant differences were observed in the use of other obstetric interventions between the two groups. There were statistically significant differences between transfer of care and the obstetric unit size. Statistically differences between the obstetric unit size and onset of labour, oxytocin stimulation, type of birth and episiotomy or perineal injury were observed. Furthermore, midwives identified several factors that complicated their task of facilitating normal birth. Barriers included: inadequate institutional support; existing obstetrician-led practices, lack of evidence-based practice and midwives’ lack of awareness of professional competencies. Factors facilitating normal birth included: midwives’ positive perceptions of normal birth, midwives’ additional effort and women’s awareness of normal birth.

Conclusions: The findings of this study should encourage a shift in the current maternity care system towards a greater integration of midwifery-led services in order to achieve optimal birth outcomes for women and newborns and potentially reduce the use of obstetric interventions in Spain.

e00014
Women, homelessness and violence: A Grounded Theory analysis of vulnerable women experience in Madrid.

Clara Isabel Posada Abadía1, Maria Teresa González Gil1, Carolina Marin Marin2

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00014

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Clara Isabel Posada Abadía, Maria Teresa González Gil, Carolina Marin Marin, et al. Women, homelessness and violence: A Grounded Theory analysis of vulnerable women experience in Madrid. IBJ Plus 2021 (S4)e0014:10.24217/2531-0151.21v1s4.00014

Edited: Madrid, España.

Abstract

Introduction: There are different processes and situations that determine and leave a mark on women trajectories and biographies setting them on a scenario of extreme vulnerability. Domestic violence conditions women live experiences and constitute a risk factor for homeless and social exclusion. Exploring the experiences of homeless women coping with vulnerability from a gender perspective will provide enriching information to develop support strategies in their recovery process. MEDSURG.52865

Material and Methods: A Grounded theory research based on Symbolic Interactionism was carried out through in depth interviews. 20 homeless women over 18 years old, who have suffered domestic violence and who were hosted in 2 different settles belonging to the Municipal Network of Madrid participated in the study. Furthermore, it was identified a meaningful and extraordinary case that was explored in deep using photo elicitation technique. Data analysis was structured in open, axial and selective coding stages using constant comparative method as reference.

Results and conclusions: Homeless women experience of coping with vulnerability in the context of life trajectories and biographies marked by gender violence can be condensed in the Basic Psychosocial Process of “Stripped of own identity, homeless and without wings” with the following stages: Living a violent childhood, Entering the spiral of partner violence, Falling into homeless. Caring interventions are required to guarantee psycho-social and spiritual needs taking in account women biographical experiences.

e00015
SMAD4 Overexpression in Patients with Sleep Apnoea May
Be Associated with Cardiometabolic Comorbidities.

Elena Díaz-García 1,2, Ana Jaureguizar 1,2, Raquel Casitas 1,2, Sara García-Tovar 2, Begoña Sánchez-Sánchez 1,2, Ester
Zamarrón 1,2, Eduardo López-Collazo 1,3, Francisco García-Río1,2,4,* and Carolina Cubillos-Zapata 1,2,*

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00015

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Elena Díaz-García, Ana Jaureguizar, Raquel Casitas, Sara García-Tovar, Begoña Sánchez-Sánchez, Ester Zamarrón, Eduardo
López-Collazo, Francisco García-Río, and Carolina Cubillos-Zapata , et al. SMAD4 Overexpression in Patients with Sleep Apnoea May
Be Associated with Cardiometabolic Comorbidities . IBJ Plus 2021 (S4)e0015:10.24217/2531-0151.21v1s4.00015.

Edited: Madrid, España.

Abstract

Introduction: Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and
cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA
patients frequently present an increase in transforming growth factor beta (TGFβ), the activity of which is higher
still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother
against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFβ
signalling pathways.

Methods. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients,
with an apnoea–hypopnoea index (AHI) ≥30 and 26 healthy volunteers.

Results. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in
HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with
the presence of diabetes, dyslipidaemia and hypertension in these patients.

Conclusion. Our results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian
rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.
Graphical abstract:

e00016
Cell Therapy for Critical Limb Ischemia (NOMA trial,
NCT04466007) and COVID-19 Pneumonia
(BALMYS-19 trial NCT04348461).

Barbara Soria-Juan1,2, *, Lucía Llanos2, Mariano Garcia-Arranz1,7, Bernat Soria3.4, Fermín Sánchez-Guijo5, Francisco
Fernández-Avilés6,Felipe Prosper7, Damian Garcia-Olmo1,8,9.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00016

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Barbara Soria-Juan, Lucía Llanos, Mariano Garcia-Arranz, Bernat Soria, Fermín Sánchez-Guijo, Francisco Fernández-Avilés,Felipe Prosper,
Damian Garcia-Olmo, et al. Cell Therapy for Critical Limb Ischemia (NOMA trial, NCT04466007) and COVID-19 Pneumonia (BALMYS-19 trial
NCT04348461) . IBJ Plus 2021 (S4)e0016:10.24217/2531-0151.21v1s4.00016.

Edited: Madrid, España.

Abstract

Introduction: Regenerative Medicine is making possible addressing unmet therapeutic needs. Mesenchymal stromal
cells (MSC) display therapeutic options addressed to the niche i) NOMA: For example, diabetic patients develop
advanced forms of critical limb ischemia that can lead to lower extremity amputation and even death. MSC secrete
growth factors that have local effects, being both angiogenic and neurotrophic. The hypothesis of this project is
that administration of allogeneic MSC will promote collateral formation of vessels improving blood flow to ischemic
tissues, ii) BALMYS-19: approximately 5% of patients with SARS-CoV-2 infection develop a very strong systemic
inflammatory phase that can progress to acute respiratory distress, together with cytokine storm, lymphopenia and
tissue damage. Preliminary data suggest that MSC reduce nonproductive inflammation and promote tissue regeneration.
Our aim was to determine whether the administration of allogeneic MSC is safe and potentially useful in
these patients.

Methods: i) A multicenter, randomized double-blind, placebo-controlled trial has been designed (NOMA clinical
trial), on the intramuscular administration of adipose tissue-derived allogeneic MSC in 90 eligible patients. Safety
and efficacy outcomes are being evaluated by measuring the rate of adverse events, and clinical, analytical and imaging-
test parameters. ii) Within the framework of a Compassionate Use program, thirteen patients with COVID-associated
pneumonia in the Intensive Care Unit were treated with intravenous allogeneic MSC. Adverse effects, clinical,
radiological and analytical parameters were collected. Both studies were approved by the Spanish Medicines Agency
and Ethics Committee from Jimenez Diaz Foundation University Hospital.
Results: i) NOMA is a clinical trial recruiting patients (Soria-Juan et al., 2019), we still do not have access to data. ii)
Regarding the Compassionate Use program for COVID-19 pneumonia, our work, published in eClinicalMedicine-The-
Lancet, included the largest cohort to date of critically ill patients with COVID-19 pneumonia receiving MSC. No
adverse events were related to MSC administration. A decrease of 85% in mortality was observed within the period
of study. Clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged
from ICU. Two patients died. Cell therapy was followed by a decrease in inflammatory parameters (C-reactive protein,
IL-6, ferritin, LDH and D-dimer) as well as an increase in lymphocytes (B, CD4+, CD8+) and an improvement in
ventilatory and radiological parameters.
Preliminary Conclusion: MSC interact with the Inflammation-Regeneration crossroad and adapt their functions to
the medical need.

e00017
Scores of risk in children with diagnosis of Kawasaki disease:
proposal from a multicentre Spanish network.

Carlos Grasa1*, Elisa Fernández-Cooke2, Sara Domínguez-Rodríguez2, Ana Barrios Tascón3,Cristina Calvo1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00017

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Carlos Grasa, Elisa Fernández-Cooke, Sara Domínguez-Rodríguez, Ana Barrios Tascón,Cristina Calvo, et al. Scores of risk in
children with diagnosis of Kawasaki disease: proposal from a multicentre Spanish network.. IBJ Plus 2021 (S4)e0017:10.24217/2531-
0151.21v1s4.00017.

Edited: Madrid, España.

Abstract

Introduction: Coronary artery aneurisms (CAA) are the main concern with Kawasaki disease (KD). There are
studies that aim to identify risk factors, but there are no established scores to predict the development of CAA.
Asian scores to predict non-responsiveness to intravenous immunoglobulin (IVIG) in patients with KD are not
useful in Western countries.
We aimed to create 2 scores to predict: risk of developing CAA, and another for failure to treatment in patients
with KD from a Western Country.

Methods: Between May 2011- June 2016, the Kawa-Race network collected retrospectively data from 625
patients diagnosed of KD in 84 Spanish hospitals. A penalized regression model was used to select the variables
for the scores. Optimal cutoffs for continuous variables were selected according to ROC curves. Weights of each
variable were calculated with multivariate logistic regression.
Scores were validated with data from 98 patients collected prospectively within the Kawa-Race network, from
January 2018-December 2019.

Results: Two scores were developed, each with different weight for the variables selected: the risk of developing
CAA is composed by 8 variables, and the score to predict failure to treatment needs 9 variables.
The score for failure to IVIG had a sensitivity 95%, specificity 34% and area under the curve (AUC) 82.6%. Validation
with the prospective cohort showed: sensitivity 78%, specificity 50% and AUC 72.7%.
The score for the risk to develop CAA had a sensitivity of 48%, specificity 81%, and AUC of 72.5%. Validation in
the prospective cohort showed: sensitivity 22%, specificity 75% and AUC 60.2%.

Conclusions: Scores able to predict failure to IVIG and/or the development of CAA will facilitate initial treatment
for children with KD. Validation of these scores in other cohorts will allow generalization of its use, selecting those
patients with higher risk of CAA or failure for a more aggressive therapy since the beginning.

e00018
Multicentric study on laparoendoscopic single-site surgery
and minilaparoscopic surgery in gynaecology. Ultra-MIS
(Ultra Minimally Invasive Surgery).

Elsa Pilar Delgado Sánchez1, Francesco Fanfani 2, Mario Malzoni 3, Aldina Couso 4, Álvaro Zapico 4, Stefano Bogliolo 5,
Damián A. Sanchez-Torres1, Bárbara Gardella5, Israel J. Thuissard-Vasallo6, Ignacio Zapardiel1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00018

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Delgado- Sánchez E., et al. Multicentric study on laparoendoscopic single-site surgery and minilaparoscopic surgery in
gynaecology. Ultra-MIS (Ultra Minimally Invasive Surgery), IBJ Plus 2021 (S4)e0018:10.24217/2531-0151.21v1s4.00018.

Edited: Madrid, España.

Abstract

Introduction:Laparoscopic surgery has become the “gold standard” approach of gynecological procedures. The next
step could be to try to be even less invasive. By reducing the number of skin incisions during surgery, such as in
laparoendoscopic single-port surgery (LESS), or by reducing the size of those incisions, such as on minilaparoscopic
surgery (Mini-LPS).
Our main objective was to compare LESS and Mini-LPS in terms of surgical time, postoperative pain and hospital
stay. Secondarily, we also analyzed the perioperative details.

Material and Methods:An international, multicentric, retrospective study was carried out. All data from patients
operated for gynecological pathology between January 1st, 2010 and December 31st, 2015 using LESS or Mini-LPS
was collected for this study retrospectively. A general comparison of all patients operated by LESS and Mini-LPS has
been performed, and a subgroup comparison according to the type of surgery: benign adnexal surgery, myomectomy,
total hysterectomy of benign cause, surgery for malignant pathology and colposacropexy.

Results:To this Symposium, we present results about the general comparison. Data from 410 patients operated
by Mini-LPS or LESS in the different collaborating centers were collected. 96 (23.2%) patients were operated by
Mini-LPS and 314 (75.8%) by LESS. In 12 (2.9 %) patients, conversion to conventional laparoscopy was performed
during surgery, 9 (9.4%) patients in the Mini-LPS group and 3 (1%) patients in the LESS group. These 12 patients were
excluded from the statistical analysis to avoid bias, but included to calculate the complication rate.
There are no statistically significant differences in the main variables of the study: surgical time, time to oral and hospital
stay. The mean surgical time in LESS group was 93,72 minutes versus 86,36 minutes in Mini-LPS groups (p 0,68).
The mean time to oral analgesia was 16,74 hour in LESS groups and 17,46 hours in Mini-LPS group (p 0,91). Mean
hospital stay was 44,95 hours in LESS group vs 38,54 hours in Mini-LPS group (p 0,23).
In the Mini-LPS group, 4 intraoperative complications were observed (1 intestinal, 1 urological and 2 vascular). In
the LESS group 4 complications were observed (1 intestinal, 2 vascular and 1 intraoperative rupture of the cyst). All
vascular complications required conversion to conventional LPS. The others were managed maintaining the same
approach. There are no significant differences between groups.

Conclusion:This study shows that it is safe to perform all types of gynecological procedures by Mini-LPS and by LESS,
with no differences between the in terms of surgical time, time to oral analgesia and hospital stay. This results motivate
to perform less invasive surgeries.

e00019
Effects of respiratory muscle training in Madrid patients
diagnosed with persistent asthma between the ages of
six and 18 years.

Córdoba S1, Varas AB2, Rodriguez MC3, Rodriguez M4, Torron D5, Talens A6..

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00019

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Córdoba S, Varas AB, Rodriguez MC, Rodriguez M, Torron D, Talens A, et al. Effects of respiratory muscle training in
Madrid patients diagnosed with persistent asthma between the ages of six and 18 years. IBJ Plus 2021 (S4)e0019:10.24217/2531-
0151.21v1s4.00019.

Edited: Madrid, España.

Abstract

Introduction: Asthma is a heterogeneous disease which affects 235.000.000 according to World Health Organization.
In pediatric population, it´s considered as the most frequent chronic pathology in western countries. It generates a
great socio-health impact on the patient and his environment. There aren´t standardized therapeutic protocols, that
identify the techniques of choice. For this reason, it´s necessary to evaluate the effects of the components of the
Pulmonary Rehabilitation Programs (PRP), in order to determine those with greater adherence and cost-efficiency.

Methods: Randomized Clinical Trial to assess the efficacy of respiratory muscle training in the study population. Subjects:
asthmatics from 6 to 17 years. Control group (CG): 9-weeks PRP that included educational sessions, Respiratory
Physiotherapy and endurance training (video game platform). Experimental group (EG): PRP identical to the CG
plus home-based respiratory muscle training (5 days/week, using threshold resistance valve). Strength and muscular
endurance were incrementally trained, using as reference values the maximum inspiratory and expiratory pressures
(MIP-MEP) evaluated preintervention. Variables: Dyspnea (modified scale of the Medical Research Council), quality
of life (Spanish version of Childhood Asthma Control Test and Pediatric Asthma Quality of Life Questionnaire), peak
expiratory flow, respiratory muscle strength (MIP-MEP), exercise tolerance (Six Minute Walking Test (6MWT)) and
exacerbations. Pre-intervention, post-intervention and follow-up measurements were performed at 6 and
12 months.

Results: 34 individuals were analyzed, CG (n=16) and EG (n=18). The average age was 9.18 years; 64.7% being woman.
The homogeneity of the groups at the beginning of the study was verified in all variables (p>0.05). An improvement
was found in the EG MIP, both post-intervention and at 12 months versus pre-intervention, with significant
difference between the groups (p<0.05). The difference adjusted according to baseline values was 16.0 cmH2O (95%
CI. 28.6; 3.4) and 16.0 cmH2O (95% CI. 28.6; 3.4), respectively. Regarding the distance of 6MWT, differences weren´t
found between the groups after the intervention, but a statistically significant 6-month maintenance was observed
in the EG (p <0.05), with an adjusted difference in the registry of 6 months vs. 44.8 m pre-intervention (95% CI. 79.0;
10.5). The rest of the variables showed slight improvement, but without significant differences between the groups.

Conclusion: Implement the specific training of the respiratory muscles in the PRP aimed at children diagnosed with
persistent asthma, increases the absolute and relative MIP values achieved, maintaining these for at least
12 months.

e00020
Application of lifestyle modification programs in
bariatric surgery.

Marta Crespo Yanguas1, Óscar Lorenzo González2, Clotilde Vázquez Martínez1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00020

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Crespo Yanguas et al. Application of lifestyle modification programs in bariatric surgery. IBJ Plus 2021 (S4)
e0020:10.24217/2531-0151.21v1s4.00020.

Edited: Madrid, España.

Abstract

Background: The usefulness of lifestyle modification programs prior to bariatric surgery (BS) is controversial,
however, large-sample retrospective studies have shown higher weight-loss that may contribute to decrease the
surgical risk.

Methodology: We used a retrospective study of patients undergoing BS by gastric bypass technique. The population
was divided into two groups, a control group without nutritional intervention (CG) and a group with nutritional
intervention consisting of a group lifestyle modification program (PGME). This program included 4 sessions
with nutritionist carried out from the beginning of the follow-up until the BS, and 6, 12 and 24 months after the
BS. The program comprised a training on healthy eating habits and physical exercise to prepare the surgery and
after it. Data were collected from the first session (V0), at the time of surgery (V1), and after 6, 12 and 24 months
of BS (V2-V3-V4).

Results: The studied population involved 121 individuals collected between 2008 and 2019 (76.9% women). The
CG included 50 patients, and the PGME, 71 subjects. The mean age was 48 (23-65) and 46 (25-64) years-old,
respectively. The mean body mass index (BMI) in V0 was 44.68 (35.19-58.83) kg/m2, with no significant differences
between the two groups. In addition, in the CG, 56% of the patients suffered from arterial hypertension
(HT), 50% from hypopnea syndrome (SAHS), 34% from dyslipidaemia (DL), and 26% from diabetes mellitus (DM).
Similarly, in the PGME, 45.1% patients suffered from HT, 53.5% from SAHS, 30% from DL, and 31.4% DM. Interestingly,
comparing V1 vs. V0 (pre-surgery state), the PGME induced a lower BMI compared to that of CG [41.94
(34.41-50.53) vs. 43.99 (35.98-57.77) kg/m2; p<0.05]. The percentage of weight loss was 6.37% in PGME while it
was 0.78% in CG (p <0.05) and the percentage of overweight lost was 16.33% in PGME and 1.93% in CG (p <0.05).
In addition, plasma levels of vitamin D increased 18.59% with PGME but only 2.92% in the CG (p <0.024). More
analysis is needed for the evolution of patients after BS, with or without PGME. Further analysis needs to be
done for the evolution of patients after BS, with or without PGME.

Conclusions: The application of a PGME prior to BS is at least effective in pre-surgery states, particularly in weight
loss and vitamin D levels. Preoperative weight loss may produce a decrease in liver size and intra-abdominal fat,
which improves surgical fields and facilitates BS. Vitamin D is essential for the formation and maintenance of
bones, but is frequently decreased after BS. Thus, PGME could be added as nutritional intervention in patients
addressed to BS.

e00021
Cigarette smoking induces chemoresistance vía α7-nicotinic
acetylcholine receptor-mediated pro-survival signaling
pathways in a non-small cell lung cancer xenograft model.

María Extremera1*, José Luis Cedillo1, Anna Bordas1, Javier Regadera2, Francisco Arnalich3 and Carmen Montiel1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00021

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: María Extremera, José Luis Cedillo, Anna Bordas, Javier Regadera, Francisco Arnalich and Carmen Montiel, et al. Cigarette
smoking induces chemoresistance vía α7-nicotinic acetylcholine receptor-mediated pro-survival signaling pathways in a non-small
cell lung cancer xenograft model. IBJ Plus 2021 (S4)e0021:10.24217/2531-0151.21v1s4.00021

Edited: Madrid, España.

Abstract

Introduction: Continue tobacco use after cancer diagnosis decreases the effectiveness of adjuvant chemotherapy
in a wide variety of smoking-related tumors, including the non-small cell lung carcinoma (NSCLC) that accounts
for 75-85% of all lung cancer cases. Previous in vitro data from our laboratory revealed that nicotine, the addictive
component of tobacco, and its carcinogenic derivative nitrosamine NNK, play a key role in the tobacco-mediated
chemoresistance by activating alpha-7 nicotinic acetylcholine receptors (α7-nAChRs) expressed in the above tumors.
The aims of the present study are to investigate: i) whether this last in vitro finding was reproduced in vivo in a nude
mouse xenograft model; and ii) which signaling pathways are involved in the α7-nAChR-mediated resistance to cisplatin
induced by nicotine.

Material and Methods: The human NSCLC cell line, lung adenocarcinoma (A549), both wild-type (A549WT) or α7-nAChR
knockout (A549KO-α7) generated by CRISPR-cas9 technology, were used. The role of α7-nAChR in the tobacco-mediated
resistance to cisplatin was assessed in vivo in an athymic mouse model implanted with A549KO-α7 or A549WT
xenograft tumors. Each group was randomized into three subgroups according to whether they receive intraperitoneal
treatment (cisplatin or cisplatin + nicotine) or not (control). Tumor volumes were measured over the 29 days
after cell injection. Then, animals were sacrificed and tumors excised for IHC and Western blot (WB) analysis of
pro-apoptotic (p53, BAX) and anti-apoptotic (survivin, XIAP) markers expression. Human apoptosis and phospho-kinase
proteome profiler arrays were used to identify signaling pathways involved in the α7-nAChR-mediated resistance
to cisplatin in A549WT or A549KO-α7 cells.

Results: Final tumor volumes of A549WT and A549KO-α7 xenografts were significantly reduced (p ≤ 0.005) by cisplatin.
Nicotine treatment partially, but significantly, prevents the cisplatin cytotoxic effect in A549WT but not in A549KO-α7
xenografts. Furthermore, IHC and WB analysis of several apoptosis markers reveals that nicotine counteracts the
pro-apoptotic effect of cisplatin by decreasing the expression of pro-apoptotic proteins and increasing that of anti-
apoptotic proteins in A549KO-α7 but not in A549WT xenografts. Finally, the addition of nicotine to cisplatin-treated
A549WT cells activates signaling cascades (Akt, RSK, PLCΎ1…) and transcription factors (c-Jun, STAT3, STAT5…) involved
in pro-oncogenic pathways. These nicotine effects do not appear in A549KO-α7 cells.

Conclusion: Our results confirm the contribution of α7-nAChRs to nicotine-induced chemoresistance in vivo and that
this effect is secondary to the activation of pro-oncogenic signaling cascades related to survival, proliferation and
inhibition of apoptosis.

e00022
A role for NCLX in NLRP3 inflammasome activation.

Narros Fernández, Paloma1,2; Irazoki, Andrea3; Farré Alins, Víctor1,2; Palomino Antolín, Alejandra1,2; Decouty Pérez,
Céline1,2; López Rodríguez, Ana Belén1,2; Zorzano, Antonio3; de los Ríos, Cristóbal1,2; Martínez Ruiz, Antonio1; Egea,
Javier1,2.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00022

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Narros Fernández, P, et al. A role for NCLX in NLRP3 inflammasome activation. IBJ Plus 2021 (S4)e0022:10.24217/2531-
0151.21v1s4.00022.

Edited: Madrid, España.

Abstract

Inflammasomes are multi-protein complexes that process and release interleukins 1β and 18. Among the different
inflammasomes, NLRP3 is the most relevant and best described. NLRP3 can be activated by different stimuli,
but all of them converge in the same route of activation, that includes intracellular ion disbalance and mitochondrial
dysfunction. The mitochondrial Na+/Ca2+ exchanger (NCLX) regulates mitochondrial calcium homeostasis
and its inhibition in hypoxic and neurotoxic conditions is beneficial in different cell types. In this context, we
asked if the modulation of NCLX activity could affect to NLRP3 inflammasome activation. We have studied NLRP3
activation in mouse bone marrow-derived macrophages (BMDMs) using the compound ITH12575, a specific inhibitor
of NCLX. NCLX inhibition prior to NLRP3 activation by ATP or MSU crystals reduces IL-1β release, ASC speck
formation, and caspase-1 processing in LPS-primed macrophages. We have corroborated these results in an in
vivo model of gout: MSU crystals (1mg) were injected subcutaneously in the paw of 3- to 5-month-old mice. 24
hours later paw inflammation, cytokine release (IL-1β and TNF-α) and NLRP3 protein expression were measured
in the paw tissue. ITH12575 3 mg/kg treatment just after MSU challenge reduced paw inflammation by 35%, as
well as cytokine production and inflammasome proteins expression.

Moreover, we have observed that mitochondrial dysfunction takes place as a consequence of NLPR3 activation,
evidenced by a decrease in the basal and ATP-linked respiration of LPS+ATP-treated BMDMs, measured by
Seahorse technology and by an increase in mitochondrial fragmentation, studied by confocal imaging. NCLX inhibition
prior to ATP addition rescues this phenotype, partially reverting bioenergetic and morphological changes
in LPS+ATP-stimulated BMDMs. We can conclude that the pharmacological inhibition of NCLX reduces NLRP3 activation
in vitro in BMDMs, and in vivo in a mouse model of gout, and that mitochondrial dysfunction is partially
rescued in NLRP3-activated macrophages by NCLX inhibition.

e00023
Toll-like receptor 4 as therapeutic target in intravascular
hemolysis-mediated acute kidney injury.

Cristina Vázquez-Carballo 1, Carmen Herencia-Bellido 1, Melania Guerrero-Hue 2, Cristina García-Caballero 2, Sandra
Rayego-Mateos 1, José Luis Morgado-Pascual 2, Mercedes Vallejo-Mudarra 2, Jesús Egido de los Ríos 1 3, Juan Antonio
Moreno 2 4 5.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00023

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Cristina Vázquez-Carballo, Carmen Herencia-Bellido, Melania Guerrero-Hue, Cristina García-Caballero, Sandra Rayego-
Mateos, José Luis Morgado-Pascual, Mercedes Vallejo-Mudarra, Jesús Egido de los Ríos, Juan Antonio Moreno, et al. Toll-like
receptor 4 as therapeutic target in intravascular hemolysis-mediated acute kidney injury. IBJ Plus 2021 (S4)e0023:10.24217/2531-
0151.21v1s4.00023.

Edited: Madrid, España.

Abstract

Massive intravascular hemolysis is a common condition of several pathologies. Regardless of etiology, intravascular
hemolysis implies the destruction of erythrocytes and massive release of free hemoglobin and heme into the
circulation. Kidneys are particularly vulnerable to injury during massive hemolysis and as result acute kidney injury
(AKI) is a common feature of hemolytic disorders. Toll-like receptor 4 (TLR4) is a key regulator of the inflammatory
response and has been associated to many cellular processes activated during AKI. We investigated the role of TLR4
in intravascular hemolysis and whether inhibition of this receptor may protect from hemolysis-mediated AKI.

We performed an experimental model of intravascular hemolysis-associated AKI promoted by intraperitoneal injection
of phenylhydrazine in TLR4 knockout mice or in combination with TLR4 inhibitor TAK-242 in wild type mice. In
these models, we evaluated renal function, histological damage, proinflammatory signaling and cell death in kidney
72 hours after the hemolysis induction. We also evaluated whether heme-mediated-inflammatory effects were prevented
by TLR4 inhibition with TAK-242 in cultured murine tubular epithelial cells.

In our experimental model, induction of massive intravascular hemolysis promoted AKI, resulting in increased blood
urea nitrogen and creatinine serum concentration, histological alterations, enhanced expression of tubular injury
markers (Kim-1, Ngal), cell death and inflammation. These pathological effects were significantly ameliorated in
TLR4-deficient mice and in wild type mice treated with TAK-242. In vitro studies showed that TAK-242 pretreatment
reduced heme-mediated inflammation by inhibiting the TLR4/NFkB axis.

Our study identifies TLR4 as a key molecule involved in the renal inflammatory response triggered by massive intravascular
hemolysis. Additionally, we proposed TLR4 inhibition as a potential therapeutic approach to prevent renal
damage in patients with severe hemolytic crisis.

e00024
PGC-1α deficiency causes spontaneous kidney inflammation
and increases the severity of nephrotoxic AKI.

Miguel Fontecha-Barriuso1,2, Diego Martin-Sanchez1,2, Julio M. Martinez-Moreno1, Susana Carrasco1,2, Olga Ruiz-
Andres1,2, Maria Monsalve3, Cristina Sanchez-Ramos3, Manuel J. Gomez4, Marta Ruiz-Ortega1,2,5, Maria D. Sanchez-
Niño1,2, Pablo Cannata-Ortiz6, Ramiro Cabello1, Carmen Gonzalez-Enguita1, Alberto Ortiz*1,2,5,7, Ana B. Sanz*1,2.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00024

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Fontecha-Barriuso M, Martín-Sánchez D, Martinez-Moreno JM, Carrasco S, Ruiz-Andrés O, Monsalve M, Sanchez-Ramos C, Gómez MJ,
Ruiz-Ortega M, Sánchez-Niño MD, Cannata-Ortiz P, Cabello R, Gonzalez-Enguita C, Ortiz A, Sanz AB. PGC-1α deficiency causes spontaneous kidney
inflammation and increases the severity of nephrotoxic AKI. J Pathol. 2019 Sep;249(1):65-78. doi: 10.1002/path.5282. Epub 2019 Jun 12. PMID:
30982966. IBJ Plus 2021 (S4)e0024:10.24217/2531-0151.21v1s4.00024.

Edited: Madrid, España.

Abstract

Massive intravascular hemolysis is a common condition of several pathologies. Regardless of etiology, intravascular
hemolysis implies the destruction of erythrocytes and massive release of free hemoglobin and heme into the
circulation. Kidneys are particularly vulnerable to injury during massive hemolysis and as result acute kidney injury
(AKI) is a common feature of hemolytic disorders. Toll-like receptor 4 (TLR4) is a key regulator of the inflammatory
response and has been associated to many cellular processes activated during AKI. We investigated the role of TLR4
in intravascular hemolysis and whether inhibition of this receptor may protect from hemolysis-mediated AKI.

We performed an experimental model of intravascular hemolysis-associated AKI promoted by intraperitoneal injection
of phenylhydrazine in TLR4 knockout mice or in combination with TLR4 inhibitor TAK-242 in wild type mice. In
these models, we evaluated renal function, histological damage, proinflammatory signaling and cell death in kidney
72 hours after the hemolysis induction. We also evaluated whether heme-mediated-inflammatory effects were prevented
by TLR4 inhibition with TAK-242 in cultured murine tubular epithelial cells.

In our experimental model, induction of massive intravascular hemolysis promoted AKI, resulting in increased blood
urea nitrogen and creatinine serum concentration, histological alterations, enhanced expression of tubular injury
markers (Kim-1, Ngal), cell death and inflammation. These pathological effects were significantly ameliorated in
TLR4-deficient mice and in wild type mice treated with TAK-242. In vitro studies showed that TAK-242 pretreatment
reduced heme-mediated inflammation by inhibiting the TLR4/NFkB axis.

Our study identifies TLR4 as a key molecule involved in the renal inflammatory response triggered by massive intravascular
hemolysis. Additionally, we proposed TLR4 inhibition as a potential therapeutic approach to prevent renal
damage in patients with severe hemolytic crisis.

e00025
Time-dependent dual effect of NLRP3 inflammasome
in brain ischemia.

Alejandra Palomino-Antolin1, Paloma Narros-Fernández1, Víctor Farré-Alins1, Javier Sevilla-Montero2, Celine
Decouty-Pérez1, Ana Belen Lopez-Rodriguez1, Nuria Fernández3, Luis Monge3, Ana I. Casas4,5, María José Calzada2,
Javier Egea1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00025

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Alejandra Palomino-Antolin, Paloma Narros-Fernández, Víctor Farré-Alins, Javier Sevilla-Montero, Celine Decouty-Pérez,
Ana Belen Lopez-Rodriguez, Nuria Fernández, Luis Monge, Ana I. Casas, María José Calzada, Javier Egea, et al. Time-dependent dual
effect of NLRP3 inflammasome in brain ischemia. IBJ Plus 2021 (S4)e0025:10.24217/2531-0151.21v1s4.00025.

Edited: Madrid, España.

Abstract

Massive intravascular hemolysis is a common condition of several pathologies. Regardless of etiology, intravascular
hemolysis implies the destruction of erythrocytes and massive release of free hemoglobin and heme into the
circulation. Kidneys are particularly vulnerable to injury during massive hemolysis and as result acute kidney injury
(AKI) is a common feature of hemolytic disorders. Toll-like receptor 4 (TLR4) is a key regulator of the inflammatory
response and has been associated to many cellular processes activated during AKI. We investigated the role of TLR4
in intravascular hemolysis and whether inhibition of this receptor may protect from hemolysis-mediated AKI.

We performed an experimental model of intravascular hemolysis-associated AKI promoted by intraperitoneal injection
of phenylhydrazine in TLR4 knockout mice or in combination with TLR4 inhibitor TAK-242 in wild type mice. In
these models, we evaluated renal function, histological damage, proinflammatory signaling and cell death in kidney
72 hours after the hemolysis induction. We also evaluated whether heme-mediated-inflammatory effects were prevented
by TLR4 inhibition with TAK-242 in cultured murine tubular epithelial cells.

In our experimental model, induction of massive intravascular hemolysis promoted AKI, resulting in increased blood
urea nitrogen and creatinine serum concentration, histological alterations, enhanced expression of tubular injury
markers (Kim-1, Ngal), cell death and inflammation. These pathological effects were significantly ameliorated in
TLR4-deficient mice and in wild type mice treated with TAK-242. In vitro studies showed that TAK-242 pretreatment
reduced heme-mediated inflammation by inhibiting the TLR4/NFkB axis.

Our study identifies TLR4 as a key molecule involved in the renal inflammatory response triggered by massive intravascular
hemolysis. Additionally, we proposed TLR4 inhibition as a potential therapeutic approach to prevent renal
damage in patients with severe hemolytic crisis.

e00026
Role of AP-1 transcription factor Fosl1 on inflammation and
nephroprotection during acute kidney injury.

Cuarental L1,2,3, Ceballos M.I.2,3, Pintor-Chocano Aranzazú2,3, Valiño-Rivas L2,3, Ortiz A1,2,3, Sánchez-Niño MD* 1,2,3.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00026

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Cuarental L, Ceballos M, Pintor-Chocano Aranzazú, Valiño-Rivas L, Ortiz A, Sánchez-Niño MD, et al. Role of AP-1 transcription factor Fosl1 on
inflammation and nephroprotection during acute kidney injury. IBJ Plus 2021 (S4)e0026:10.24217/2531-0151.21v1s4.00026.

Edited: Madrid, España.

Abstract

Introduction: Fosl1 (also known as FRA1 (Fos-related-antigen 1) is a transcription factor of the AP-1 complex (activator
protein 1). Fosl1 regulates the expression of multiple target genes involved in differentiation, inflammation, proliferation
and cell death. AKI (acute kidney injury) is characterized by the overexpression of inflammatory cytokines and the
downregulation of the anti-aging and nephroprotective protein Klotho. We have now explored the role of Fosl1 in AKI,
including its role in the regulation of nephroprotective factors.

Methods and results: Fosl1 was found upregulated in experimental nephrotoxic AKI transcriptomics and Fosl1 upregulation
was confirmed (RT-qPCR; immunohistochemistry) in experimental and human AKI and localized to tubular
cell nuclei. The function of Fosl1 was explored in murine nephrotoxic AKI in genetically modified mice. Fosl1 deficient
(Fosl1Δtub) mice in kidney tubular cells developed more severe AKI and kidney leukocyte infiltration induced by
either folic acid or cisplatin. Additionally, kidney expression of the nephroprotective and antiaging factor Klotho was
more severely depressed in Fosl1Δtub mice. In tubular cells cultured in an inflammatory milieu, Fosl1 expression was
upregulated. Fosl1 siRNA targeting in cultured tubular cells increased inflammatory gene expression and cell death and
decreases Klotho expression.

Conclusion: In conclusion, Fosl1 contributes to an adaptive kidney response that limits kidney injury during AKI.

e00027
Activation of the mTOR-mitochondria axis in the diabetic and
hypertensive cardiomyopathy.

Hang T1, Corrales S1, Azkargorta M2, Lumpuy-Castillo J1, Elortza F2, Martínez-Chantar M2, and Lorenzo O1.
1.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00027

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Hang T, Corrales S, Azkargorta M, Lumpuy-Castillo J, Elortza F, Martínez-Chantar M, and Lorenzo , et al. Activation
of the mTOR-mitochondria axis in the diabetic and hypertensive cardiomyopathy. IBJ Plus 2021 (S4)e0027:10.24217/2531-
0151.21v1s4.00027.

Edited: Madrid, España.

Abstract

Introduction: Type 2 Diabetes Mellitus (T2DM) and hypertension (HTN) can lead to cardiac dysfunction and eventually
heart failure. Patients with both T2DM and HTN may have even a worse prognosis than those with T2DM or
HTN alone. Inflammation, hypertrophy, apoptosis and fibrosis are common cardiac responses in these pathologies.
However, the involved molecular mechanisms have not been fully depicted.

Methodology: Cardiac biopsies from interventricular septum were isolated from patients with T2DM and /or HTN
during coronary artery bypass grafting. Control samples were isolated from non-T2DM or -HTN individuals. Then, the
differential protein expression was evaluated by proteomics (hybrid trapped ion mobility spectrometry) and PEAKS
software. Ingenuity Pathway Analysis (IPA, Qiagen) was used to predict the implication of molecular pathways. Cultured
cardiomyocytes were used to reveal the alteration of relevant pathways under different conditions. Stimulation
with high glucose (HG), high fatty-acid (HF) and/or angiotensin-II mimicked the hyperglycemic, hyperlipidemic and
pro-hypertensive milieu, respectively.

Results: Cardiac samples from HTN patients showed an increase of 4 proteins and a decrease of 41 compared to
controls. Samples from T2DM/HTN subjects exhibited an increase of 117 proteins and a reduction of 549. Proteins
were clustered in molecular pathways. HTN induced a decrease of cardiac factors related to carbohydrate metabolism,
mitochondrial homeostasis and respiration, while T2DM/HTN reduced the expression of enzymes involved in
fatty acid and glucose metabolism, as well as mitochondrial proteins of respiration and ATP synthesis. Also, T2DM/
HTN increased fibrosis and apoptosis related factors. Interestingly, in cultured cardiomyocytes under stimulation
with HG, HF and/or AngII we confirmed by Western Blot the alterations of mitochondrial factors such as TFAM,
ACADm, MFN2, and SDHA. In addition, HF and Ang II, but not HG, enhanced the phosphorylation on Thr389 of
P70S6, a mTORC1 downstream mediator. However, the phosphorylation on Ser473 of Akt (a mTORC2 downstream
mediator) was ameliorated by HF or Ang II, but elevated by HG.

Conclusion: T2DM/ HTN can lead to dramatic protein changes in heart. The changes in the myocardial tissue could
be more significant when both pathologies are combined. At least, the mitochondrial alteration may be responsible
of cardiac dysfunction. In particular, the mTORC1 complex may activated to reduce mitochondrial factors (i.e., TFAM)
and related metabolic enzymes (ACADm and SDHA), leading to a lack in ATP synthesis and cardiac dysfunction. The
regulation of the mTOR-mitochondria axis could be essential for prognosis of heart failure in T2DM and
HTN patients.

e00028
FAT-1 transgenic mice are protected against vascular damage
in hypertension.

Lucía Serrano Díaz del Campo1, Ana B. García-Redondo1,2,3, Mercedes Salaices1,2,3, Ana M. Briones1,2,3.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00028

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Díaz Del Campo LS, et al. FAT-1 transgenic mice are protected against vascular damage in hypertension. IBJ Plus 2021 (S4)
e0028:10.24217/2531-0151.21v1s4.00028.

Edited: Madrid, España.

Abstract

Introduction: Vascular functional and structural alterations induced by hypertension are greatly influenced by
low-grade chronic inflammation. Resolution of inflammation is mediated by specialized lipid pro-resolving mediators
(SPMs), which derive from n3 fatty acids (PUFAs). The transgenic fat-1 mice express a n3 desaturase which
converts n6 into n3 fatty acids, resulting in greater level of anti-inflammatory mediators in their tissues. Previous
evidence from our group and others suggest that SPM prevent vascular damage in several pathological situations
including atherosclerosis or vascular restenosis.
The aim of this study was to evaluate the effects of AngII in blood pressure and cardiovascular damage in a model
with elevated SPM.

Material and methods: aortas, mesenteric resistance arteries (MRA) and heart were taken from heterozygous
transgenic fat-1 mice and its corresponding wild type (WT) littermates infused or not with AngII (1,44mg/kg/
day; 14 days). Blood pressure was measured by tail-cuff plethysmography. Vascular function and structure were
studied with wire and pressure myographs, confocal analysis and histological staining. Cardiac hypertrophy was
measured using tibial length. Gene expression was analyzed with RT-PCR.

Results: We observed that fat-1 mice were partially protected against the AngII-induced increase in blood pressure
but not in the development of cardiac hypertrophy. Moreover, AngII induced endothelial dysfunction in
aorta and mesenteric resistance arteries (MRA) from WT but not in fat-1 mice. Similarly, AngII increased vascular
contractile response in aortas from WT but this hypercontractility was prevented in fat-1 genotype. In addition,
AngII increased wall thickness more in WT mice compared to fat-1. No differences in structural parameters of
MRA between WT and fat-1 mice were observed, but, fat-1 mice were protected against AngII-induced vascular
stiffness, possibly by attenuation AngII-induced increase in fenestrae area in the adventitial layer. In addition,
SPM reduced AngII-induced leukocyte infiltration, as shown by a reduction in runx1 and cd163 gene expression
levels in perivascular adipose tissue and general reduction of proinflammatory cytokines expression in aorta.

Conclusion: In conclusion, our data shows the potential protective role of SPM in vascular stiffness, endothelial
dysfunction and inflammation associated with hypertension.

e00029
Soluble dipeptidyl peptidase 4 (sDPP4) as inducer of vascular inflammaging: a role for NLRP3 inflammasome.

Inés Valencia1,2,3, Pilar Dongil1,2, Susana Vallejo1,2, Alejandra Romero1,2, Álvaro San Hipólito-Luengo1,2,3, Marta
Menéndez1,2, Licia Shamoon1,2,3, Tania Romacho1,2, Concepción Peiró1,2, Carlos F. Sánchez-Ferrer1,2.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00029

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Inés Valencia, Pilar Dongil, Susana Vallejo, Alejandra Romero, Álvaro San Hipólito-Luengo, Marta Menéndez, Licia Shamoon, Tania Romacho,
Concepción Peiró, Carlos F. Sánchez-Ferrer, et al. Soluble dipeptidyl peptidase 4 (sDPP4) as inducer of vascular inflammaging: a role for NLRP3
inflammasome. IBJ Plus 2021 (S4)e0029:10.24217/2531-0151.21v1s4.00029.

Edited: Madrid, España.

Abstract

Introduction. Inflammaging defines a state of uncontrolled low-grade chronic inflammation that exacerbates the
age-related disorders. Obesity and type 2 diabetes mellitus accelerate vascular aging, leading to premature vascular
dysfunction. In these diseases, adipose tissue enlargement favours the secretion of pro-inflammatory adipokines
such as soluble dipeptidyl peptidase 4 (sDPP4). We have previously determined that sDPP4 may contribute to vascular
disease by promoting human vascular smooth muscle cells inflammation and proliferation, but its implication
in this context of inflammaging is unknown. In this study, we evaluated whether sDPP4 promotes endothelial cell
senescence and dysfunction, hallmarks of vascular aging, and studied the underlying mechanisms. Since the NLRP3
inflammasome has been proposed to participate in the inflammatory status underlying cardiometabolic diseases, we
hypothesized that NLRP3 inflammasome and its final product IL-1β could mediate sDPP4-induced
detrimental effects.

Materials and Methods. We evaluated sDPP4-induced endothelial senescence and its mechanisms of action in vitro
in human umbilical vein endothelial cells (HUVEC). We determined senescence-associated-β-galactosidase activity,
DNA damage, senescence-associated secretory phenotype (SASP) and pro-senescence markers expression. NLRP3
inflammasome upregulation and activation was determined by western blot and immunofluorescence. Moreover,
we used human isolated mesenteric microvessels to study vascular function in reactivity experiments.

Results. sDPP4 (200 ng/ml) induced endothelial senescence in vitro and impaired endothelium-dependent relaxation
ex vivo in a mechanism dependent on its enzymatic activity. In HUVEC, sDPP4 promoted the expression of the
inflammasome components NLRP3, ASC, pro-IL-1β and caspase-1 and its activation as determined by ASC-speck
formation. Both senescence and impaired reactivity were prevented by the DPP4 inhibitor linagliptin (10 nmol/l) and
by both the NLRP3 assembly inhibitor MCC950 (1 μmol/l) and the IL-1R antagonist anakinra (1 μg/ml).

Conclusion. Our results show the implication of NLRP3 inflammasome and its product IL-1β in mediating sDPP4-induced
vascular senescence and dysfunction. Antidiabetic DPP4 inhibitors, as well as NLRP3 inflammasome-targeted
drugs, arise as potential therapeutic interventions for tackling the inflammaging scenario associated to cardiometabolic
diseases.

e00030
ITH12575: a promising neuroprotective compound acting
over Ca2+ dyshomeostasis and mitochondrial NCLX.

Lucía Viejo1,2,*, Raquel L. Arribas2, Cristóbal de los Ríos1,2..

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00030

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Lucía Viejo, Raquel L. Arribas, Cristóbal de los Ríos, et al. ITH12575: a promising neuroprotective compound acting over Ca2+ dyshomeostasis
and mitochondrial NCLX. IBJ Plus 2021 (S4)e0030:10.24217/2531-0151.21v1s4.00030.

Edited: Madrid, España.

Abstract

INTRODUCTION: During aging, Ca2+ homeostasis is gradually impaired. This is even exacerbated in neurodegenerative
diseases, affecting especially to neurons. Among all mechanisms regulating Ca2+, the Na+/Ca2+ mitochondrial
exchanger (NCLX) has been presented as a novel target. NCLX releases Ca2+ from mitochondrial matrix to
cytosol. Our group has synthesized derivatives of the NCLX classical modulator CGP37157, increasing its selectivity
and solubility, with the goal of studying Ca2+ modulation capacity and the neuroprotective properties of the
NCLX partial blockade. Its best new derivative ITH12575 has been selected to deepen into those pharmacological
properties.

MATERIALS AND METHODS: In vitro assays were conducted in the cell line SH-SY5Y or in primary cultures of
cortical neurons form rat or mouse embryos. Calcium flow experiments were made with the dye Fluo-4AM. For
neuroprotection, high concentrations of glutamate (50 μM), the stressor cocktail comprised by rotenone and
oligomycin A (R/O, 30 μM/10 μM) or okadaic acid (20 nM) were selected as toxic stimuli, measuring cell viability
by the MTT method. Specificity test were assessed using siRNA and mouse NCLX KO cortical neurons. Effect over
mitochondria metabolism was evaluated by the Seahorse method.

RESULTS: ITH12575 reduced cytosolic Ca2+ oscillations in a dose-dependent manner when cultures were stimulated
by high K+ concentration or NMDA, with IC50 of 3.34 μM and 15.33 μM (respectively). As for neuroprotective
assays, ITH12575, from 1 μM diminished cell death induced by the toxic stimuli used. Compound selectivity for
NCLX was evaluated by two approaches: first, silencing NCLX using a siRNA and measuring ITH12575 protective
effect against R/O. When NCLX is not present in cells, ITH12575 was not able to recover cell viability. Secondly,
cortical neurons from KO NCLX and wild type mice were used to establish differences in Ca2+ overload modulation.
ITH12575, at 10 μM, did not avoid Ca2+ elevations in KO NCLX neurons while it maintained its reduction in
WT ones. Finally, in the Seahorse experiments, ITH12575 seems to restore both basal respiration and maximum
respiration capacity of mitochondria from SH-SY5Y cells under high K+ concentrations. Besides, the compound
increased ATP production under this toxic environment.

CONCLUSIONS: ITH12575 has proved to decrease Ca2+ overload caused by high K+ or NMDA, and to improve
cell viability against several toxic models. As for its selectivity, the experiments demonstrated that it has a mayor
action over NCLX. This action could be reflected in the potential improve of mitochondrial metabolism under
stress situation evoked by K+. Thus, ITH12575 seems to be a promising neuroprotective compound that should
be considered for in vivo evaluation.

e00031
Development of an organ bath technique to assess intestinal
motility in isolated mouse ileum and colon.

Raquel Gómez Bris 1,2,3; Beatriz Herrero Fernandez 1,2,3; Pilar Rodriguez Rodriguez 2; Ángela Sáez 1,4; Silvia Arribas 2,*;
José María Gonzalez Granado 1,2,3,5.*.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00031

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Raquel Gómez Bris, Beatriz Herrero Fernandez , Pilar Rodriguez Rodriguez , Ángela Sáez , Silvia Arribas, José María Gonzalez Granado, et al.
Development of an organ bath technique to assess intestinal motility in isolated mouse ileum and colon. IBJ Plus 2021 (S4)e0031:10.24217/2531-
0151.21v1s4.00031.

Edited: Madrid, España.

Abstract

The organ bath is a traditional experimental set-up that is commonly used to investigate the physiology and pharmacology
of in vitro tissue preparations. Typical experiments involve the addition of drugs to the organ bath or direct/
field stimulation of the tissue. The tissue reacts by contracting/relaxing, and an isometric or isotonic transducer is
used to measure force or displacement, respectively1. Inflammatory bowel disease (IBD) is a chronic inflammatory
disease of the intestine that comprises ulcerative colitis and Crohn’s disease. Patients with IBD suffer frequently from
functional and motility disorders, resulting in diminished quality of life and sometimes narcotics use2. RAG1 is the
V(D)J recombination activation gene, therefore Rag1-/- mice do not contain mature B and T lymphocytes3. Here we
describe the use of organ bath to study the impact of IBD and the particular role of B and T lymphocytes in intestinal
motility in a Dextran Sodium Sulphate (DSS) mice model of colitis.
Wild-type and Rag1-/- mice were fed 2% (w/v) DSS in their drinking water for 5 days, followed by 3–7 days of water
consumption. Mice were divided into three groups: control group (received only water), acute group (killed at day
8 upon DSS administration) and recovery group (killed at day 12 upon DSS administration). Mice body weight and
disease symptoms were monitored daily. Upon sacrifice, intestine (from ileum to the anus) was isolated and stored
in cold Krebs solution. Ileum and colon were cleaned and divided in four fragments each. Each fragment was mounted
in an organ bath channel with Krebs solution and O2 supply and allowed to equilibrate until the development of
spontaneous contractions or for at least 40 min. Contraction in response to potassium was measured by the substitution
of Krebs solution with a 120mM KCl solution; and contraction in response to muscarinic agonists, carbachol
and acetylcholine, was studied with drug dosage curve from 10-9 M to 10-4 M. At the end of the experiment, Krebs
without calcium was used to obtain basal line. Data were acquired and analysed with LabChart 8 software (ADInstruments
Ltd).
Differences in intensity and frequency of basal contractions and in response to stimuli are observed between wildtype
and colitis groups and comparing wildtype and Rag1-/- mice, both in ileum and in colon.
In conclusion, an organ bath system seems to be a suitable approach to study IBD-associated intestinal motility
changes and IBD alters intestinal motility due to, at least in part, the effect of T and B lymphocytes.
References:
1. ADInstruments Ltd
2. Abdalla. 2016. Gastrointest Endosc Clin N Am.
3. Mombaerts. 1992. Cell.

e00032
Transcriptomic Analysis of the Epileptogenic Zone of Drug
Resistant Epilepsy Patients Subjected to Neurosurgery.

Patricia Sánchez-Jiménez1, Marcos Elizalde-Horcada2, Gemma Benito1, Javier Fraga3, Inmaculada Granero-Cremades4,
Cristina Virginia Torres5, María de Toledo6, Paloma Pulido5, Marta Navas5, Francisco Abad-Santos2,7, Antonio Gómez-
Martín1, Paolo Maietta1, María del Carmen Ovejero-Benito*2,8.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00032

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Patricia Sánchez-Jiménez, Marcos Elizalde-Horcada, Gemma Benito, Javier Fraga, Inmaculada Granero-Cremades, Cristina Virginia Torres,
María de Toledo, Paloma Pulido, Marta Navas, Francisco Abad-Santos, Antonio Gómez-Martín, Paolo Maietta, María del Carmen Ovejero-
Benito, et al. Transcriptomic Analysis of the Epileptogenic Zone of Drug Resistant Epilepsy Patients Subjected to Neurosurgery. IBJ Plus 2021 (S4)
e0032:10.24217/2531-0151.21v1s4.00032.

Edited: Madrid, España.

Abstract

Introduction: Epilepsy is a chronic neurological disease that affects 0.5% of world population. One of third of these patients
suffer from drug resistant epilepsy (DRE). Surgical resection of the epileptogenic zone is an effective therapeutic
approach for DRE patients. Thus, it is important to understand the molecular mechanisms underlying drug resistance.
For that purpose, we have performed a transcriptomic analysis in hippocampal samples of patients with drug-resistant
temporal lobe epilepsy (TLE).

Materials and methods: 46 FFPE samples were obtained from TLE patients that had been subjected to the neurosurgical
resection of the epileptogenic zone. As a control group, we used 36 FFPE post-mortem hippocampus from subjects
who did not suffer from any neurological or neurodegenerative disease (Navarra Biomed, IMIB, IDIBAPs and Puerta de
Hierro biobanks). RNA was extracted from the samples with truXTRAC® FFPE total NA kit (Covaris). Total RNA-seq libraries
were prepared using SMARTer® Stranded Total RNA-Seq kit v2-Pico Input Mammalian (Takara Bio). Quality control
and quantification were performed before and after library preparation using the TapeStation 2200 (Agilent Technologies)
and the Qubit 2.0 Fluorometer (Thermo Fisher Scientific). Libraries were sequenced to an average depth of 100
million total reads (PE 100 bp) on the Illumina NovaSeqTM 6000 platform. Sequencing reads were aligned to GRCh37
reference genome applying HISAT2 and StringTie to obtain counts matrix. Sequences’ quality control was performed
before and after aligned, excluding 1 patient and 13 controls with less than 5% of sequence alignment. Differential expressed
genes (DEGs) were analyzed with DESeq2 to compare TLE and control samples and adjusted by False discovery
rate (FDR) and Bonferroni corrections. We selected the top genes of DEGs for validation by RT-qPCR in our cohort.

Results: We analyzed samples from 45 patients and 22 controls, which mean age were 46.1±10.5 and 49.1±14.8 yearsold,
respectively. Before neurosurgery, these patients had an average of 4.5 seizures/month, and five of them had
30-90 seizures/month. We also found that 31 (69%) of patients were seizure-free after surgery and 39 (87%) reached
Engel I after two years. After applying FDR test to RNA-seq analysis, we obtained 6,709 significant DEGs of which 3,111
were upregulated and 3,598 were downregulated. Gene ontology and pathway enrichment were performed to these
DEGs and we found 30 GO-IDs and 32 pathways enriched, most of them were implicated in synapsis-related process
and brain-related mechanisms. At the moment we are currently validating these results. This analysis will help us to
confirm our findings of differentially expressed genes involved in DRE.

e00033
Olive leaf (Olea europaea L.) extract addition to extra virgin
olive and algae oils mixture decreases fatty acid oxidation
and synergically attenuates age-induced hypertension
and vascular dysfunction.

Daniel González-Hedström1,2*, Sara Amor1, María de la Fuente-Fernández1, Ángel Luís García-Villalón1, Miriam
Granado1,3..

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00033

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Daniel González-Hedström , Sara Amor, María de la Fuente-Fernández, Ángel Luís García-Villalón, Miriam Granado, et al. Olive leaf (Olea
europaea L.) extract addition to extra virgin olive and algae oils mixture decreases fatty acid oxidation and synergically attenuates age-induced
hypertension and vascular dysfunction. IBJ Plus 2021 (S4)e0033:10.24217/2531-0151.21v1s4.00033.

Edited: Madrid, España.

Abstract

Introduction: Aging is associated with an increase in visceral adiposity and a decrease in muscle mass and brown
adipose tissue, in addition to an increase in the risk of suffering cardiovascular diseases. Thus, there is great interest
in finding possible treatments of natural origin to alleviate it, with fewer side effects than conventional pharmacological
treatments. Various studies link the consumption of omega-3 polyunsaturated fatty acids (ω‐3 PUFA) and
olive by-products as extra virgin olive oil (EVOO) and olive leaf extracts (OLE) with a decrease in the risk of suffering
adverse cardiovascular and metabolic diseases. In addition, olive by-products constitute an interesting ingredient to
stabilize ω‐3 PUFA and decrease their oxidation process due to its high content in antioxidant compounds.

Materials and Methods: In this study, we aimed to study the possible increase of oxidative stability of ω‐3 PUFA in
an oil mixture composed by EVOO (75%) and algae oil (AO; 25%) rich in ω‐3 PUFA (35% docosahexaenoic acid (DHA)
and 20% eicosapentaenoic acid (EPA)) with the addition of an olive leaves extract (10% of hydroxytyrosol and 1 mg/g
of luteolin-7-o-glucoside). Also, we evaluate the improvement on the cardiometabolic alterations associated with
aging when these ingredients are administrated altogether. For this purpose, young (three months old) and old (24
months old) male Wistar rats were treated with vehicle or with the oil mixture (2.5 mL/kg) and the OLE (100 mg/Kg)
for 21 days.

Results: OLE reduced the increase in primary and secondary oxidation of fatty acids in the oil mixture through time.
Administration of the nutraceutical compound to aged rats prevented the aging-induced loss of body weight and
muscle mass, and the aging induced increase in visceral white adipose tissue (WAT). In addition, the treatment
decreased aging-induced increase in medial arterial pressure, and serum triglycerides, and LDL and total cholesterol,
together with an increase of adiponectin levels. Treated old rats showed an improvement of insulin response in WAT
and gastrocnemius muscle, through p-Akt pathway, and in the liver, due to an increase in p-GSK3β phosphorylation.
In aorta segments, treatment prevented aging induced endothelial dysfunction, vascular insulin resistance and
increased noradrenalin response. All these changes were associated with an improvement in the gene expression of
inflammatory and antioxidant enzymes due to the nutraceutical compounds on old rats.

Conclusions: In conclusion, the supplementation of a mixture of AO rich in ω‐3 PUFA and EVOO with an OLE not only
improves its oxidative stability but also improves some of the cardiometabolic alterations associated with aging in
treated rats with it.

e00034
Microsomal Prostaglandin E Synthase-1 (mPGES-1) plays
a key role in the development of renal, metabolic and
cardiovascular alterations associated with obesity..

Ballesteros-Martinez C1 , Rodrigues-Diez R1,2,3 , Martínez-Martínez E4 , Beltrán L5 , Gonzalez-Amor M1, Cachofeiro V3,4,
Salaices M1,2,3, Briones AM1,2,3.

Published May 21, 2021.

DOI: 10.24217/2531-0151.21v1s4.00034

Copyright: © 2021 Author. This is an open-access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite as: Ballesteros-Martinez C , Rodrigues-Diez R , Martínez-Martínez E , Beltrán L5 , Gonzalez-Amor M, Cachofeiro V, Salaices M, Briones AM, et al.
Microsomal Prostaglandin E Synthase-1 (mPGES-1) plays a key role in the development of renal, metabolic and cardiovascular alterations associated
with obesity. IBJ Plus 2021 (S4)e0034:10.24217/2531-0151.21v1s4.00034.

Edited: Madrid, España.

Abstract

Introduction: Obesity is a risk factor for the development of metabolic and cardiovascular alterations. Microsomal
prostaglandin E synthase 1 (mPGES-1) is responsible for the production of prostaglandin E2 (PGE2) under inflammatory
conditions. PGE2 is a key lipid mediator that participates in vascular damage associated to inflammatory
processes. This study evaluates the role of mPGES-1 in the development of metabolic and cardiovascular alterations
associated with obesity.

Material and methods: We developed a model of high-fat diet (HFD, 60% fat)-induced obesity in male mPGES-1-/-
and mPGES-1+/+ mice. The glycaemic profile was studied by glucose and insulin tolerance tests. Vascular function,
and structural and mechanical properties of aorta and mesenteric resistance arteries (MRAs) were evaluated by
isometric and perfusion myographs. Histological studies, q-RT-PCR and Western Blot analyses were performed. Gene
expression in abdominal fat from patients and its correlation with vascular damage was determined.

Results: Our results show that mPGES-1-/- mice fed with HFD are protected against body weight gain and present
better glycaemic profile compared to mPGES-1+/+ mice. At cardiovascular level mPGES-1-/- mice are protected against
vascular functional and structural alterations, vascular remodelling and inflammation, and cardiac hypertrophy and
fibrosis induced by HFD. Moreover, mPGES-1-/- mice are protected against renal fibrosis and inflammation, and glomerular
remodelling. In patients, mPGES-1 expression in abdominal fat positively correlates with vascular remodelling
and stiffness, and with systolic blood pressure.

Conclusion: Our data suggest that mPGES-1 could be a novel therapeutic target to prevent some of the metabolic,
renal and cardiovascular alterations associated with obesity.