Publications by authors named "Beatriz Moreno"

55 Publications

Tomato Domestication Affects Potential Functional Molecular Pathways of Root-Associated Soil Bacteria.

Plants (Basel) 2021 Sep 17;10(9). Epub 2021 Sep 17.

Department of Environmental Protection, Estación Experimental del Zaidín (EEZ), CSIC, C/Profesor Albareda 1, 18008 Granada, Spain.

While it has been well evidenced that plant domestication affects the structure of the root-associated microbiome, there is a poor understanding of how domestication-mediated differences between rhizosphere microorganisms functionally affect microbial ecosystem services. In this study, we explore how domestication influenced functional assembly patterns of bacterial communities in the root-associated soil of 27 tomato accessions through a transect of evolution, from plant ancestors to landraces to modern cultivars. Based on molecular analysis, functional profiles were predicted and co-occurrence networks were constructed based on the identification of co-presences of functional units in the tomato root-associated microbiome. The results revealed differences in eight metabolic pathway categories and highlighted the influence of the host genotype on the potential functions of soil bacterial communities. In general, wild tomatoes differed from modern cultivars and tomato landraces which showed similar values, although all ancestral functional characteristics have been conserved across time. We also found that certain functional groups tended to be more evolutionarily conserved in bacterial communities associated with tomato landraces than those of modern varieties. We hypothesize that the capacity of soil bacteria to provide ecosystem services is affected by agronomic practices linked to the domestication process, particularly those related to the preservation of soil organic matter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants10091942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472556PMC
September 2021

Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation.

Genes (Basel) 2021 Aug 30;12(9). Epub 2021 Aug 30.

Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital, 28040 Madrid, Spain.

Haploinsufficiency of has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of is well established, clinical features of patients harboring sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98% of patients, microcephaly in 65%, feeding difficulties in 62%, ADHD or hyperactivity in 54%, and autistic traits in 52%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3' end of the gene, confirming the genotype-phenotype correlation initially described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12091360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471078PMC
August 2021

Association of chemokines IP-10/CXCL10 and I-TAC/CXCL11 with insulin resistance and enhance leukocyte endothelial arrest in obesity.

Microvasc Res 2021 Sep 15;139:104254. Epub 2021 Sep 15.

INCLIVA Biomedical Research Institute, Valencia, Spain; Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Valencia, Spain; CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- ISCIII, Madrid, Spain; Department of Medicine, Faculty of Medicine, University of Valencia, Spain. Electronic address:

Background And Aims: Obesity is a key contributing factor to incidental type 2 diabetes and cardiovascular disease. CXCR3 receptor and its ligands CXCL 10 and 11 are associated with atherosclerosis and cardiovascular disease. The aim of our study was to analyse the role of the CXCR3 ligands on insulin resistance (IR) and endothelial dysfunction in human obesity.

Methods And Results: We have studied 45 obese patients (mean age 44 ± 6 years, body mass index 45 ± 9 kg/m) who were selected for Roux-Y-gastric bypass surgery and 21 non obese control subjects with similar age and gender distribution. We measured by ELISA the circulating levels of the CXCR3 ligands interferon-γ inducible protein 10 (IP-10/CXCL10) and interferon-γ-inducible T-cell alpha chemoattractant (I-TAC/CXCL11). Using an ex vivo procedure with the flow chamber assay, we have investigated the effect of such chemokines on endothelial leukocytes arrest under dynamic conditions. Peripheral blood levels of CXCL10 and CXCL11 were significantly higher in obese subjects than in controls (p < 0.001) and significantly correlated with BMI, waist circunference and HOMA-IR. Obese patients with HOMA-IR index above 75th percentile showed highest increase of circulating CXCL10 and CXCL11 values. Under dynamic flow conditions, the enhanced adhesion of patient leukocytes to TNFα-induced human arterial endothelial cells was partly dependent on CXCR3.

Conclusions: The study demonstrates that CXCL10 and CXCL11 are associated with IR and enhance leukocyte endothelial arrest in obese subjects. Blockade of CXCR3 signaling might be a new therapeutic approach for the prevention of obesity-associated cardiovascular co-morbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mvr.2021.104254DOI Listing
September 2021

Microscale Toxicity Identification Evaluation (TIE) for interstitial water of estuarine sediments affected by multiple sources of pollution.

Environ Sci Pollut Res Int 2021 Sep 12. Epub 2021 Sep 12.

Departamento de Ciências do Mar, Instituto do Mar, Universidade Federal de São Paulo (UNIFESP), Campus Baixada Santista, R. Dr. Carvalho de Mendonça, 144, Vila Belmiro, CEP 11070-102, Santos, São Paulo, Brazil.

Estuaries in the world are affected by different contamination sources related to urbanisation and port/industrial activities. Identifying the substances responsible for the environmental toxicity in estuaries is challenging due to the multitude of stressors, both natural and anthropogenic. The Toxicity Identification and Evaluation (TIE) is a suitable way of determining causes of toxicity of sediments, but it poses difficulties since its application is labour intensive and time consuming. The aim of this study is to evaluate the diagnosis provided by a TIE based on microscale embryotoxicity tests with interstitial water (IW) to identify toxicants in estuarine sediments affected by multiple stressors. TIE showed toxicity due to different combinations of metals, apolar organic compounds, ammonia and sulphides, depending on the contamination source closest to the sampling station. The microscale TIE was able to discern different toxicants on sites subject to different contamination sources. There is good agreement between the results indicated in the TIE and the chemical analyses in whole sediment, although there are some disagreements, either due to the sensitivity of the test used, or due to the particularities of the use of interstitial water to assess the sediment toxicity. The improvement of TIE methods focused on identifying toxicants in multiple-stressed estuarine areas are crucial to discern contamination sources and subsidise management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-15389-xDOI Listing
September 2021

TOCSY, hydrogen decoupling and computational calculations to an unequivocal structural elucidation of a new sesquiterpene derivative and identification of other constituents from Praxelis sanctopaulensis.

Phytochem Anal 2021 Aug 7. Epub 2021 Aug 7.

Departamento de Química, Universidade Estadual de Maringá, Maringá, PR, Brazil.

Introduction: Praxelis genus comprises 24 species, however, only two species of this genus have been chemically investigated. Here we investigated Praxelis sanctopaulensis, a native plant from Brazil, that occurs mainly in Cerrado regions.

Objective: The goal was to identify the specialised metabolites from P. sanctopaulensis, and compare with those described from Praxelis and Chromolaena species.

Methods: The phytochemical study of P. sanctopaulensis was performed through different chromatography techniques, including high-performance liquid chromatography (HPLC), gas chromatography flame ionisation detector (GC-FID), and ultra-high-performance liquid chromatography high-resolution tandem mass spectrometry (UHPLC-HRMS/MS). The structures of the compounds were established based on spectroscopic analysis, total correlated spectroscopy (TOCSY), hydrogen decoupling and computational calculations was used to an unequivocal structural elucidation of a new sesquiterpene. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP), and antimicrobial assay was performed by the microdilution method. Comparison of the flavonoids described P. sanctopaulensis was carried out using principal component analysis.

Results: The phytochemical investigation of P. sanctopaulensis led to the isolation of a pair of diastereomers, praxilone A and praxilone B. Seven known compounds were isolated from this species, another 14 fatty acids were detected in hexane fraction, and 26 compounds were identified from ethyl acetate fraction. All these compounds are being described for the first time in this species, with the exception of viridifloric acid. The ethyl acetate fraction showed potent antioxidant activity.

Conclusions: Forty-seven compounds are described from P. sanctopaulensis. The combination of different techniques of nuclear magnetic resonance (NMR) spectroscopy and computational calculations allowed the unequivocal structure elucidation of a new cadinene. The clustering analysis showed similarities between the flavonoids identified in P. sanctopaulensis and in Chromolaena species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pca.3082DOI Listing
August 2021

Surgical Trainee Performance and Alignment With Surgical Program Director Expectations.

Ann Surg 2021 Jun 16. Epub 2021 Jun 16.

Department of Surgery, Center for Surgical Training and Research, University of Michigan, Ann Arbor, Michigan University of Michigan Medical School, Ann Arbor, Michigan Department of Learning Health Sciences, University of Michigan, Ann Arbor, Michigan Consulting for Statistics, Computing, and Analytics Research, University of Michigan, Ann Arbor, Michigan American Board of Surgery, Philadelphia, Pennsylvania American Board of Medical Specialties Chicago, Illinois University of Melbourne Medical School, Melbourne, Victoria University of Queensland Faculty of Medicine, Brisbane, Queensland Department of Surgery, Northwestern University, Chicago, Illinois.

Objective: To examine the alignment between graduating surgical trainee operative performance and a prior survey of surgical program director expectations.

Background: Surgical trainee operative training is expected to prepare residents to independently perform clinically important surgical procedures.

Methods: We conducted a cross-sectional observational study of US general surgery residents' rated operative performance for Core general surgery procedures. Residents' expected performance on those procedures at the time of graduation was compared to the current list of Core general surgery procedures ranked by their importance for clinical practice, as assessed via a previous national survey of general surgery program directors. We also examined the frequency of individual procedures logged by residents over the course of their training.

Results: Operative performance ratings for 29,885 procedures performed by 1,861 surgical residents in 54 general surgery programs were analyzed. For each Core general surgery procedure, adjusted mean probability of a graduating resident being deemed practice-ready ranged from 0.59 to 0.99 (mean 0.90, standard deviation 0.08). There was weak correlation between the readiness of trainees to independently perform a procedure at the time of graduation and that procedure's historical importance to clinical practice (ρ = 0.22, 95% confidence interval 0.01-0.41, P = 0.06). Residents also continue to have limited opportunities to learn many procedures that are important for clinical practice.

Conclusion: The operative performance of graduating general surgery residents may not be well aligned with surgical program director expectations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004990DOI Listing
June 2021

Is Initial Board Certification Associated With Better Early Career Surgical Outcomes?

Ann Surg 2021 08;274(2):220-226

Center for Surgical Training and Research, Department of Surgery, University of Michigan, Ann Arbor, Michigan.

Objective: To determine if initial American Board of Surgery certification in general surgery is associated with better risk-adjusted patient outcomes for Medicare patients undergoing partial colectomy by an early career surgeon.

Background: Board certification is a voluntary commitment to professionalism, continued learning, and delivery of high-quality patient care. Not all surgeons are certified, and some have questioned the value of certification due to limited evidence that board-certified surgeons have better patient outcomes. In response, we examined the outcomes of certified versus noncertified early career general surgeons.

Methods: We identified Medicare patients who underwent a partial colectomy between 2008 and 2016 and were operated on by a non-subspecialty trained surgeon within their first 5 years of practice. Surgeon certification status was determined using the American Board of Surgery data. Generalized linear mixed models were used to control for patient-, procedure-, and hospital-level effects. Primary outcomes were the occurrence of severe complications and occurrence of death within 30 days.

Results: We identified 69,325 patients who underwent a partial colectomy by an early career general surgeon. The adjusted rate of severe complications after partial colectomy by certified (n = 4239) versus noncertified (n = 191) early-career general surgeons was 9.1% versus 10.7% (odds ratio 0.83, P = 0.03). Adjusted mortality rate for certified versus noncertified early-career general surgeons was 4.9% versus 6.1% (odds ratio 0.79, P = 0.01).

Conclusion: Patients undergoing partial colectomy by an early career general surgeon have decreased odds of severe complications and death when their surgeon is board certified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004709DOI Listing
August 2021

Mussels get higher: A study on the occurrence of cocaine and benzoylecgonine in seawater, sediment and mussels from a subtropical ecosystem (Santos Bay, Brazil).

Sci Total Environ 2021 Feb 23;757:143808. Epub 2020 Nov 23.

Laboratório de Ecotoxicologia, Universidade Santa Cecília, Rua Oswaldo Cruz 266, 11045-907 Santos, Brazil; Departamento de Ciências do Mar, Universidade Federal de São Paulo, Rua Maria Máximo, 168, 11030-100 Santos, Brazil. Electronic address:

Data on the occurrence of cocaine (COC) and benzoylecgonine (BE) in marine environmental compartments are still limited, with few studies reporting superficial water contamination, mainly in tropical zones. In this sense, environmental data of these substances are essential to identify potential polluting sources, as well as their impact in costal ecosystems. The aim of this study was to evaluate the occurrence of COC and BE in seawater, sediment and mussels from a subtropical coastal zone (Santos Bay, São Paulo, Brazil), as well as to determine a field measured Bioaccumulation Factor (BAF). COC and BE were detected in all water samples in concentrations ranging from 1.91 ng·L to 12.52 ng·L and 9.88 ng·L to 28.53 ng·L, respectively. In sediments, only COC was quantified in concentrations ranging from 0.94 ng·g to 46.85 ng·g. Similarly, only COC was detected in tissues of mussels 0.914 μg·kg to 4.58 μg·kg (ww). The field-measured BAF ranged from 163 to 1454 (L·kg). Our results pointed out a widespread contamination by cocaine and its main human metabolite benzoylecgonine in Santos Bay. Mussels were able to accumulate COC in areas used by residents and tourists for bathing, fishing, and harvest, denoting concern to human health. Therefore, our data can be considered a preliminary assessment, which indicates the need to evaluate drugs (including illicit as COC) in environmental and seafood monitoring programs, in order to understand their risks on the ecosystem and human health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.143808DOI Listing
February 2021

Aptamers Against Live Targets: Is In Vivo SELEX Finally Coming to the Edge?

Mol Ther Nucleic Acids 2020 Sep 23;21:192-204. Epub 2020 May 23.

Molecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of Navarra, Pamplona 31008, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de Navarra, Pamplona 31008, Spain. Electronic address:

Targeted therapeutics underwent a revolution with the entry of monoclonal antibodies in the medical toolkit. Oligonucleotide aptamers form another family of target agents that have been lagging behind in reaching the clinical arena in spite of their potential clinical translation. Some of the reasons for this might be related to the challenge in identifying aptamers with optimal in vivo specificity, and the nature of their pharmacokinetics. Aptamers usually show exquisite specificity, but they are also molecules that display dynamic structures subject to changing environments. Temperature, ion atmosphere, pH, and other variables are factors that could determine the affinity and specificity of aptamers. Thus, it is important to tune the aptamer selection process to the conditions in which you want your final aptamer to function; ideally, for in vivo applications, aptamers should be selected in an in vivo-like system or, ultimately, in a whole in vivo organism. In this review we recapitulate the implementations in systematic evolution of ligands by exponential enrichment (SELEX) to obtain aptamers with the best in vivo activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2020.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321788PMC
September 2020

Effects of Microplastics Associated with Triclosan on the Oyster Crassostrea brasiliana: An Integrated Biomarker Approach.

Arch Environ Contam Toxicol 2020 Jul 11;79(1):101-110. Epub 2020 Apr 11.

Department of Marine Sciences, Federal University of São Paulo, Santos, São Paulo, Brazil.

Urban waste is a complex mixture of different substances, including microplastics and pharmaceuticals and personal care products. Microplastics have a high affinity for hydrophobic substances. One of these substances is triclosan, a bactericide used in a variety of hygiene products. Therefore, microplastics (MPs) may serve as a vector between triclosan and aquatic organisms. The current study sought to evaluate the effects of the interaction between microplastics and triclosan based on a mechanistic approach in which the oyster Crassostrea brasiliana was used as a model. The organisms were exposed to three conditions: the control, microplastic (MP), and microplastic contaminated with triclosan (MPT). The organisms were exposed for 3 or 7 days. After the exposure time, hemolymph was sampled for performing the neutral red retention time assay and, subsequently, the gills, digestive glands, and adductor muscles were dissected for measuring biomarkers responses (EROD, DBF, GST, GPx, GSH, lipid peroxidation, DNA strand breaks, and AChE). Our results demonstrate combined effects of MPs associated with triclosan on oyster physiology and biochemistry, as well as on lysosomal membrane stability. These results contribute to understanding the effects of contaminants of emerging concern and microplastics on aquatic organisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00244-020-00729-8DOI Listing
July 2020

Lead toxicity on a sentinel species subpopulation inhabiting mangroves with different status conservation.

Chemosphere 2020 Jul 3;251:126394. Epub 2020 Mar 3.

Universidade Federal de São Paulo, Departamento de Ciências do Mar, Campus Baixada Santista, Rua Maria Máximo, 168, Ponta da Praia, Santos, SP, 11030-100, Brazil; Universidade Santa Cecília, Laboratório de Ecotoxicologia, Rua Oswaldo Cruz, 266, Santos, SP, 11045-907, Brazil. Electronic address:

Lead is a priority pollutant introduced in the aquatic environment by different sources commonly located in estuarine regions, such as ports, marinas and industries. Environmental agencies around the world set the maximum allowable concentration of lead in effluents, surface water and sediment, but few studies reported its accumulation and chronic toxicity in mangrove benthic invertebrates using concentrations believed to be safe. In the case of Brazilian mangrove environments, Ucides cordatus is a crab species of choice to be used in bioaccumulation studies. We have assessed biomarkers' responses (DNA strand breaks, micronucleated cells, metallothioneins, enzymatic activity of aminolevulinic acid dehydratase and neutral red retention time) and the total bioaccumulation in six tissues of U. cordatus crabs resident to mangrove areas under different conservation status during a 28-day period bioassay. We also investigated Pb subcellular partition and biomarkers' responses using a supposedly safe concentration (10 μg L). During the Pb exposure, the highest concentration of Pb was observed in crab gills. Crabs also showed a high ability to allocate Pb in detoxified forms. Multivariate analysis pointed out that bioaccumulation (total, active and detoxified) is linked to biomarkers. Even in supposedly safe dosage, U. cordatus triggered its defense mechanisms expressing more metallothioneins and presented relevant cyto-genotoxic damage. Our data suggest the development of biological tolerance to Pb in crabs from polluted areas. Our results provided a new insight about lead toxicity even at concentrations considered environmentally safe, which could support new strategies to manage estuarine areas considering their respective conservation status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.126394DOI Listing
July 2020

Author Correction: The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction.

Stem Cell Rev Rep 2020 06;16(3):626

Stem Cell Therapy Unit, Jesus Uson Minimally Invasive Surgery Centre, Cáceres, Spain.

The original version of this article unfortunately contained a mistake. In the author group, the correct family name of Dr. Rebeca is "Blázquez" and the correct family name of Dr. Francisco Miguel is "Sánchez-Margallo."
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-020-09962-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645569PMC
June 2020

Inflammatory and antioxidant pathway dysfunction in borderline personality disorder.

Psychiatry Res 2020 02 11;284:112782. Epub 2020 Jan 11.

Biomedical Research Networking Consortium for Mental Health (CIBERSAM), Hospital Gregorio Marañón, Pabellón de Gobierno 1ª Planta C/Dr. Esquerdo 46, 28007 Madrid, Spain; Department of Psychiatry and Medical Psychology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Ciudad Universitaria s/n, 28040 Madrid, Spain.

Introduction: This study investigates the alteration of the inflammatory/oxidative pathway in patients with borderline personality disorder (BPD) and its relationship with clinical features of the disorder.

Methods: 49 BPD patients and 33 healthy control subjects were studied. Plasma levels of TBARS, nitrites, and the antioxidant enzymes CAT, GPx and SOD were measured. In addition, peripheral blood mononuclear cells were obtained to investigate levels of intracellular components of the inflammatory/oxidative pathway including the IκBα, NFκB, iNOS, COX2, Keap1, NQO1, and HO1. Western Blot and ELISA were used to measure protein expression. Patients were assessed for different clinical dimensions of BPD with scales for depression, anxiety, impulsivity and functioning.

Results: A significant decrease of IκBα levels and a significant increase of inflammatory factors, including NFκB, COX2 and iNOS levels were found in patients. On the other hand, a significant decrease was observed for all antioxidant enzymes in patients with BPD, except for HO1. The inflammatory factor NFκB showed a significant positive correlation with impulsivity scores.

Conclusions: Patients with BPD presented an increased activation of several components of the inflammatory pathways, as well as an inhibition of the antioxidant path. These alterations appear partially correlated with the impulsivity scores in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2020.112782DOI Listing
February 2020

Functioning of autobiographical memory specificity and self-defining memories in people with cancer diagnosis.

PeerJ 2019 19;7:e8126. Epub 2019 Dec 19.

Department of Psychology, University of Castilla-La Mancha, Albacete, Spain.

Objectives: Cognitive and emotional disturbances have been associated with the diagnosis and treatment of cancer. Autobiographical memory is one of the specific cognitive processes affected during this disease. The current study had two main aims: (1) to compare the functioning of autobiographical memory specificity and its related variables (executive functioning, depression and perceived stress) in a group of persons with cancer and a control group; and (2) to analyze whether the experience of cancer evolved into a self-defining memory in the sample of participants diagnosed with this disease.

Method: The study sample comprised 62 participants, 31 in the group with a cancer diagnosis and 31 in the control group. Autobiographical memory specificity, executive functions, depression, stress and self-defining memory were evaluated in the current study.

Results: Depressive symptomatology and reduced executive functioning, but not perceived stress levels, are related and are predictors of autobiographical memory specificity. In addition, the identified characteristics of the self-defining memories were associated with the cancer experience as a threat to physical integrity and an awareness of the meaning of life.

Conclusion: This emerging research line is especially important in view of its possible impacts on patients' well-being, due to the importance of psychological processes in cancer disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.8126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925954PMC
December 2019

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction.

Stem Cell Rev Rep 2020 06;16(3):612-625

Stem Cell Therapy Unit, Jesus Uson Minimally Invasive Surgery Centre, Cáceres, Spain.

Acute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as "pro-regenerative cells" with a pro-angiogenic and anti-inflammatory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-019-09926-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253530PMC
June 2020

Seasonal monitoring of cocaine and benzoylecgonine in a subtropical coastal zone (Santos Bay, Brazil).

Mar Pollut Bull 2019 Dec 5;149:110545. Epub 2019 Sep 5.

Laboratório de Ecotoxicologia, Universidade Santa Cecília, Rua Oswaldo Cruz 266, 11045-907 Santos, Brazil; Departamento de Ciências do Mar, Universidade Federal de São Paulo, Rua Maria Máximo, 168, 11030-100 Santos, Brazil. Electronic address:

Illicit drugs and their metabolites represent a new class of emerging contaminants. These substances are continuously discharged into wastewater which have been detected in the aquatic environment in concentrations ranging from ng.L to μg.L. Our study detected the occurrence of cocaine (COC) and benzoylecgonine (BE) in a subtropical coastal zone (Santos Bay, SP, Brazil) within one year. Water samples (surface and bottom) were collected from the Santos Submarine Sewage Outfall (SSOS) area. COC and BE were measured in the samples using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-ESI-MS/MS). Concentrations ranged from 12.18 to 203.6 ng.L (COC) and 8.20 to 38.59 ng.L (BE). Higher concentrations of COC were observed during the end of spring, following the population increase at summer season. COC and its metabolite occurrence in this coastal zone represent a threat to coastal organisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2019.110545DOI Listing
December 2019

Common snook juveniles, Centropomus undecimalis, as biomonitor organisms to evaluate cytogenotoxicity effects of surface estuarine water from Southern Brazil.

Mar Pollut Bull 2019 Dec 24;149:110513. Epub 2019 Aug 24.

Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.

Centropomus undecimalis fish inhabit the highly contaminated Santos-São Vicente Estuarine System (SESS) and could be a good biomonitor of contaminants. This study aimed to investigate the cytogenotoxic potential of superficial water from SESS using C. undecimalis as a biomonitoring model and to validate the use of farmed fish as controls. Using biochemical (DNA damage and Lipid Peroxidation - LPO), cellular (erythrocyte nuclear abnormality - ENA) and tissue (8-OHdG immunoexpression) biomarkers, our results showed fish from SEES had higher LPO concentration in gills and higher frequency of reniform, lobed and total ENA in erythrocytes when compared with control farmed fish. Thus, SESS surface water are cytogenotoxic for blood and gills cells of fishes. C. undecimalis has shown to be a good biomonitor model and farmed fish can be used as control only if livers were not the target organs of study since the dietary food from farmed fish causes steatosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2019.110513DOI Listing
December 2019

ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity.

Mol Ther 2019 11 25;27(11):1878-1891. Epub 2019 Jul 25.

Molecular Therapeutics Program, Center for Applied Medical Research, CIMA, University of Navarra, Pamplona 31008, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Recinto de Complejo Hospitalario de Navarra, Pamplona 31008, Spain. Electronic address:

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymthe.2019.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838990PMC
November 2019

Marine contamination and cytogenotoxic effects of fluoxetine in the tropical brown mussel Perna perna.

Mar Pollut Bull 2019 Apr 6;141:366-372. Epub 2019 Mar 6.

Universidade Santa Cecília, Rua Oswaldo Cruz 266, Santos, SP CEP:11045-907, Brazil; Universidade Federal de São Paulo, Rua Maria Máximo 168, Santos, SP CEP 11030-100, Brazil. Electronic address:

Concerns are growing about the presence of fluoxetine (FLX) in environmental matrices, as well as its harmful effects on non-target organisms. FLX in aquatic ecosystems has been detected in a range varying from pg/L to ng/L, while adverse effects have been reported in several organisms inhabiting freshwater and marine environments. The present study quantifies FLX concentrations in seawater samples from Santos Bay, Brazil and assesses metabolic responses and sublethal effects on the tropical brown mussel Perna perna. Levels of ethoxyresorufin‑O‑deethylase, dibenzylfluorescein dealkylase, glutathione S-transferase, glutathione peroxidase, cholinesterase, lipoperoxidation, and DNA damage were assessed in the gills and digestive gland of these animals, and lysosomal membrane stability was also assessed in hemocytes. FLX altered phase I and II enzyme activities, caused cytogenotoxic effects, and negatively impacted the overall health of mussels exposed to environmentally relevant concentrations. These findings contribute to characterize the risks of introducing this drug into the marine environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.marpolbul.2019.02.065DOI Listing
April 2019

Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.

Neurotherapeutics 2019 07;16(3):808-827

Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Cientificas, Barcelona, 08034, Spain.

The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we identified the small molecule BN201 that promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. Moreover, BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. In summary, we provide a new promising strategy to promote neuroaxonal survival and remyelination, potentially preventing disability in brain diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13311-019-00717-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694325PMC
July 2019

Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I.

Vaccine 2018 08 10;36(32 Pt B):4944-4951. Epub 2018 Jul 10.

Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address:

Background: Cuba has a new pneumococcal conjugate vaccine candidate (PCV7-TT). This study evaluates the safety and immunogenicity in healthy infants using 2p+1 vaccination schedule.

Methods: A phase I, controlled, randomized and double blind clinical trial was designed. 30 unvaccinated healthy infants were included. 20 subjects were assigned to study group (PCV7-TT) and 10 to control group (Synflorix®) to receive the vaccines at 7, 8 months of age (primary series) and 11 months (booster dose). Blood samples were collected 30 days after second dose and post booster for antibodies measure analysis by ELISA and OPA. The statistics analysis included the frequency of occurrence for adverse events and the immune response. Non-parametric tests were used to compare the immune response. The clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 available at http://registroclinico.sld.cu.

Results: Overall, the safety profile of PCV7-TT was similar to Synflorix®. Local reactions were predominant and systemic events were mild in severity. Swelling and redness were frequently associated with PCV7-TT mainly after the first dose (50% and 40% respectively). 15% and 10% of subject reported severe swelling after first dose with PCV7-TT and after second dose with Synflorix®. Mild fever (≥38-≤39), vomiting and sleep disturb were the systemic events reported. 100% of infants achieved pneumococcal IgG antibody concentrations ≥0.35 µg/ml after booster dose for serotypes 1, 14, 18C and 19F in each vaccine group. For serotypes 5, 6B and 23F, more than 80% infants vaccinated with Synflorix® or PCV7-TT achieved protective IgG GMC ≥ 0.35 µg/ml after booster dose. OPA proportion's responders to the seven common serotypes were 89.5% or more after the primary dose and 100% after booster dose in vaccinated with PCV7-TT.

Conclusions: The Cuban PCV7-TT is safe, well tolerated and immunogenic in healthy infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2018.05.027DOI Listing
August 2018

Ecotoxicological effects of losartan on the brown mussel Perna perna and its occurrence in seawater from Santos Bay (Brazil).

Sci Total Environ 2018 Oct 22;637-638:1363-1371. Epub 2018 May 22.

Unisanta - Universidade Santa Cecília, Santos, SP, Brazil; Unifesp - Universidade Federal de São Paulo, Santos, SP, Brazil. Electronic address:

The antihypertensive losartan (LOS) has been detected in wastewater and environmental matrices, however further studies focused on assessing the ecotoxicological effects on aquatic ecosystems are necessary. Considering the intensive use of this pharmaceutical and its discharges into coastal zones, our study aimed to determine the environmental concentrations of LOS in seawater, as well as to assess the biological effects of LOS on the marine bivalve Perna perna. For this purpose, fertilization rate and embryolarval development were evaluated through standardized assays. Phase I (ethoxyresorufin O‑deethylase EROD and dibenzylfluorescein dealkylase DBF) and II (glutathione S-transferase GST) enzymes, glutathione peroxidase (GPx), Cholinesterase (ChE), lipoperoxidation (LPO) and DNA damage were used to analyze sublethal responses in gills and digestive gland of adult individuals. Lysosomal membrane stability was also assessed in hemocytes. Our results showed the occurrence of LOS in 100% of the analyzed water samples located in Santos Bay, Sao Paulo, Brazil, in a range of 0.2 ng/L-8.7 ng/L. Effects on reproductive endpoints were observed after short-term exposure to concentrations up to 75 mg/L. Biomarker responses demonstrated the induction of CYP450 like activity and GST in mussel gills exposed to 300 and 3000 ng/L of LOS, respectively. GPx activity was also increased in concentration of exposure to 3000 ng/L of LOS. Cyto-genotoxic effects were found in gills and hemocytes exposed in concentrations up to 300 ng/L. These results highlighted the concern of introducing this class of contaminants into marine environments, and pointed out the need to include antihypertensive compounds in environmental monitoring programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2018.05.069DOI Listing
October 2018

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

J Clin Hypertens (Greenwich) 2018 05 5;20(5):910-917. Epub 2018 May 5.

Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.

This study aimed to evaluate the effects of glycated hemoglobin (HbA ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.13293DOI Listing
May 2018

Detoxification, oxidative stress, and cytogenotoxicity of crack cocaine in the brown mussel Perna perna.

Environ Sci Pollut Res Int 2019 Sep 8;26(27):27569-27578. Epub 2018 Mar 8.

Departamento de Ciências do Mar, Universidade Federal de São Paulo, Rua Maria Máximo, 168, Santos, 11030-100, Brazil.

The presence of cocaine and its metabolites and by-products has been identified in different aquatic matrices, making crack cocaine the target of recent studies. The aim of this study was to evaluate the sublethal effects of crack on the brown mussel Perna perna. Mussels were exposed to three concentrations of crack cocaine (0.5, 5.0, and 50.0 μg L) for 168 h. Gills, digestive glands, and hemolymph were extracted and analyzed after three different exposure times using a suite of biomarkers (EROD, DBF, GST, GPX, LPO, DNA damage, ChE, and lysosomal membrane stability [LMS]). After 48 and 96 h of exposure, EROD, DBF, GST, GPX activities and DNA strand breaks in the gills increased significantly after 48 and 96 h of exposure. Alterations in LMS were also observed in the mussels exposed to all crack concentrations after 96 and 168 h. Our results demonstrated that crack cocaine is metabolized by CYP-like and GST activities in the gills. GPX was not able to prevent primary genetic damage, and cytotoxic effects in the hemocytes were also observed in a dose- and time-dependent response. Our study shows that the introduction of illicit drugs into coastal ecosystems must be considered a threat to marine organisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-018-1600-7DOI Listing
September 2019

Do thiazide diuretics reduce central systolic blood pressure in hypertension?

J Clin Hypertens (Greenwich) 2018 01 6;20(1):133-135. Epub 2017 Nov 6.

Department of Internal Medicine, Hypertension Clinic, State Medical School of São José do Rio Preto (FAMERP), São Paulo, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.13134DOI Listing
January 2018

Correction to: the disruption of mitochondrial axonal transport is an early event in neuroinflammation.

J Neuroinflammation 2017 10 23;14(1):206. Epub 2017 Oct 23.

Center of Neuroimmunology, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Cellex Building, Laboratory 3A, Casanova 145, 08036, Barcelona, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-017-0979-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654101PMC
October 2017

Mechanisms Involved in the Remyelinating Effect of Sildenafil.

J Neuroimmune Pharmacol 2018 03 3;13(1):6-23. Epub 2017 Aug 3.

Institute of Biotechnology and Biomedicine and Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain.

Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is. Using myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a MS model, we previously showed that daily administration of sildenafil starting at peak disease rapidly ameliorates clinical symptoms while administration at symptoms onset prevents disease progression. These beneficial effects of the drug involved down-regulation of adaptive and innate immune responses, protection of axons and oligodendrocytes (OLs) and promotion of remyelination. In this work we have investigated mechanisms involved in the remyelinating effect of sildenafil. Using demyelinated organotypic cerebellar slice cultures we demonstrate that sildenafil stimulates remyelination by direct effects on CNS cells in a nitric oxide (NO)-cGMP-protein kinase G (PKG)-dependent manner. We also show that sildenafil treatment enhances OL maturation and induces expression of the promyelinating factor ciliary neurotrophic factor (CNTF) in spinal cord of EAE mice and in cerebellar slice cultures. Furthermore, we demonstrate that sildenafil promotes a M2 phenotype in bone marrow derived macrophages (BMDM) and increases myelin phagocytosis in these cells and in M2 microglia/macrophages in the spinal cord of EAE mice. Taken together these data indicate that promotion of OL maturation directly or through induction of growth factor expression, regulation of microglia/macrophage inflammatory phenotype and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue and further support the contention that this well tolerated drug could be useful for ameliorating MS pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11481-017-9756-3DOI Listing
March 2018

Bottom-up effects on herbivore-induced plant defences: a case study based on compositional patterns of rhizosphere microbial communities.

Sci Rep 2017 07 24;7(1):6251. Epub 2017 Jul 24.

Estación Experimental del Zaidín (EEZ), CSIC, 18008, Granada, Spain.

Below-ground soil microorganisms can modulate above-ground plant-insect interactions. It still needs to be determined whether this is a direct effect of single species or an indirect effect of shifts in soil microbial community assemblages. Evaluation of the soil microbiome as a whole is critical for understanding multi-trophic interactions, including those mediated by volatiles involving plants, herbivorous insects, predators/parasitoids and microorganisms. We implemented a regulated system comprising Nerium oleander plants grown in soil initially containing a sterile/non sterile inoculum, herbivore Aphis nerii and predator Chrysoperla carnea. After aphid attack, plants emitted a characteristic blend of volatiles derived from two biosynthetic classes: fatty acid catabolites and aromatic-derived products. Three aliphatic compounds were mainly detected in plants grown in the inoculated microbial soil, a blend which was preferentially chosen by C. carnea adult females. The contrasting effect of the initial inocula was attributed to the different microbial consortia developed in each treatment. We argue that differences in the relative abundance of the active microbial communities in the rhizosphere correlate with those in the emission of selected volatile compounds by attacked plants. The mechanisms involved in how the functional soil microbiome modulates inducible indirect defence of plants are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-06714-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524984PMC
July 2017

First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases.

Sci Transl Med 2016 12;8(370):370ra184

Centro de Biología Molecular Severo Ochoa, Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM), Madrid, Spain.

Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest that inhibiting an immediate TCR signal has promise for treating a broad spectrum of human T cell-mediated autoimmune and inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aaf2140DOI Listing
December 2016

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress.

Neurotherapeutics 2016 10;13(4):833-843

Department of Pharmacology, Faculty of Medicine, University Complutense, 28040, Madrid, Spain.

Alterations in the innate inflammatory response may underlie the pathophysiology of psychiatric diseases. Current antipsychotics modulate pro-/anti-inflammatory pathways, but their specific actions on these pathways remain only partly explored. This study was conducted to elucidate the regulatory role of paliperidone (1 mg/kg i.p.) on acute (6 h) and chronic (6 h/day for 21 consecutive days) restraint stress-induced alterations in 2 emerging endogenous anti-inflammatory/antioxidant mechanisms: nuclear factor erythroid-related factor 2 (NRF2)/antioxidant enzymes pathway, and the cytokine milieu regulating M1/M2 polarization in microglia, analyzed at the mRNA and protein levels in prefrontal cortex samples. In acute stress conditions, paliperidone enhanced NRF2 levels, possibly related to phosphoinositide 3-kinase upregulation and reduced kelch-Like ECH-associated protein 1 expression. In chronic conditions, paliperidone tended to normalize NRF2 levels through a phosphoinositide 3-kinase related-mechanism, with no effects on kelch-Like ECH-associated protein 1. Antioxidant response element-dependent antioxidant enzymes were upregulated by paliperidone in acute stress, while in chronic stress, paliperidone tended to prevent stress-induced downregulation of the endogenous antioxidant machinery. However, paliperidone increased transforming growth factor-β and interleukin-10 in favor of an M2 microglia profile in acute stress conditions, which was also corroborated by paliperidone-induced increased levels of the M2 cellular markers arginase I and folate receptor 2. This latter effect was also produced in chronic conditions. Immunofluorescence studies suggested an increase in the number of microglial cells expressing arginase I and folate receptor 2 in the stressed animals pretreated with paliperidone. In conclusion, the enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13311-016-0438-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081131PMC
October 2016
-->