Publications by authors named "María Cruz"

368 Publications

Personalised Prophylaxis in a Child with Haemophilia A and Type 1 Diabetes.

Clin Pract 2021 May 8;11(2):287-292. Epub 2021 May 8.

Hemophilia Foundation of Salta, Salta 4400, Argentina.

Poor management of either type 1 diabetes or haemophilia A can lead to complications such as organ dysfunction and haemarthropathy. Here, we describe the case of an 8-year-old boy diagnosed with severe haemophilia A shortly after birth. At 2 years old, he was also diagnosed with type 1 diabetes. After six years, the haemophilia treatment was changed from a plasma-derived factor VIII (FVIII) concentrate (octanate, Octapharma, Lachen, Switzerland) to Nuwiq (simocotocog alfa, Octapharma, Lachen, Switzerland), a recombinant FVIII (rFVIII) product from a human cell line, which allowed for a personalised treatment schedule that supported good adherence. The dosing regimen could be reduced to two weekly rFVIII infusions. The patient has experienced no spontaneous bleeds since switching to rFVIII and shows no signs of joint damage after over seven years of FVIII prophylaxis. rFVIII was well tolerated, with no treatment-related adverse events observed. This case illustrates the importance of treatment personalisation for young patients and their families managing concomitant diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/clinpract11020041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161436PMC
May 2021

Socio-economic and environmental factors associated with the occurrence of canine infection by Leishmania infantum in Teresina, Brazil.

Vet Parasitol Reg Stud Reports 2021 Apr 27;24:100561. Epub 2021 Mar 27.

Departamento de Morfofisiologia Veterinária, Programa de Pós-graduação em Tecnologias Aplicadas a Animais de Interesse Regional, Universidade Federal do Piauí, Centro de Ciências Agrárias, Campos Socopo- S/N, 64049-550 Teresina, Piauí, Brazil. Electronic address:

American visceral leishmaniasis (AVL) is a zoonosis caused by protozoan parasites of the genus Leishmania. In Brazil, the disease is caused by Leishmania infantum and the main vector is the phlebotomine sandfly Lutzomyia longipalpis, found both in natural ecotopes and in the rural and urban environments, being very well adapted to the peridomestic environment. The domestic dog has been incriminated as the main reservoir of the parasite in the urban environment, but the control measures based on culling seropositive dogs have not shown to be effective to contain the spread of the disease throughout the country. Many studies evaluated risk factors for human visceral leishmaniasis but few focused on the socioeconomic and environmental factors associated with infection among dogs. Knowledge of these factors might help identify the conditions that contribute to the maintenance of transmission cycles in the urban environment and identify new targets for intervention. The objective of this study was to assess the association between socioeconomic and environmental factors and the occurrence of canine leishmaniasis at Teresina city, Brazil. This cross-sectional study was developed in ten districts of Teresina, involving 532 houses and 810 dogs. Peripheral blood samples were collected by vein punction using vacutainer tubes without anticoagulant for performing serological test (indirect immunofluorescence - IFI). Serum samples with IFI titers ≥1: 80 were considered positive. Owners of the selected dwellings were interviewed using a semi-structured questionnaire addressing socioeconomic and environment aspects. The association between variables and seropositivity was assessed through multilevel logistic regression models. Global seropositivity was 39%. There was no statistically significant difference between seropositivity and age and sex of animals, literacy of the household head, presence of other domestic animals or with household characteristic like water supply, inadequate sewage disposal system, type of floor and roof. Mixed-breed dogs and those living for a long time in houses with absence of masonry walls and presence of a kennel showed higher odds of seropositivity. These results suggest that some peridomestic characteristics, especially the absence of barriers that allow dogs to have free access to the street, in association with the presence of a kennel, might contribute to maintaining the infection cycle in urban areas. Intervention measures oriented to the management of the peridomestic environment and responsible dog possession could be useful tools for reducing disease burden in endemic area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vprsr.2021.100561DOI Listing
April 2021

-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems.

Open Med (Wars) 2021 12;16(1):640-650. Epub 2021 Apr 12.

Sahlgrenska University Hospital, Gothia Forum for Clinical Research, Gothenburg, Sweden.

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through -regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/med-2021-0264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051167PMC
April 2021

Chemical characterization and bioactive potential of Artemisia campestris L. subsp. maritima (DC) Arcang. essential oil and hydrodistillation residual water.

J Ethnopharmacol 2021 Aug 28;276:114146. Epub 2021 Apr 28.

University of Coimbra, Faculty of Pharmacy of University of Coimbra, Coimbra, Portugal; LAQV, REQUIMTE, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. Electronic address:

Ethnopharmacological Relevance: Artemisia campestris L. is widely used in traditional medicine for their anti-inflammatory, antirheumatic, antimicrobial and antioxidant properties. A. campestris subsp. maritima Arcang., a halophyte plant ("madorneira" or "erva-lombrigueira" in Portugal), is traditionally used for gastric disorders, rheumatism and hypertension.

Aim Of The Study: The present study aims to characterize the essential oil (EO) and the hydrodistillation residual water (HRW), a by-product of the EO production, of Artemisia campestris subsp. maritima from Portugal and evaluate the antioxidant, antifungal, anti-inflammatory and wound healing activities of both extracts at concentrations without toxicity.

Materials And Methods: The phenolic profile of HRW was determined by HPLC-PDA-ESI/MS and the EO was analyzed by gas chromatography (GC-FID and GC-MS). The antioxidant activity of both extracts were determined by several assays (ABTS, NO FRAP, β-carotene and DPPH). The antifungal activity (MIC and MLC) was evaluated against yeasts, dermatophytes and Aspergillus strains using broth macrodilution methods. The anti-inflammatory potential was determined measuring the nitric oxide (NO) production by stimulated mouse leukemic macrophages (RAW 264.7). Cell viability was evaluated for RAW 264.7 and mouse fibroblasts (NIH/3T3). The wound healing activity was evaluated in mouse fibroblasts (NIH/3T3) by the scratch assay.

Results: The HRW is mainly characterized by hydroxycinnamic acids and the essential oil is characterized by high amounts of β-pinene (54.5%), cadin-4-en-7-ol (9.5%), Z-β-ocimene (6.0%) and Ƴ-terpinene (4.6%). Both extracts showed high antioxidant potential in different assays. Additionally, only the hydrodistillation residual water showed anti-inflammatory activity (IC of 330 μg/mL). On the other hand, only the EO showed antifungal activity, particularly against Epidermophyton floccosum (MIC and MLC values of 0.16 μL/mL), and wound healing activity. Bothe extracts were not cytotoxic to macrophages CONCLUSIONS: The by-product HRW contains safe bioactive compounds with antioxidant and anti-inflammatory effect and the EO shows antioxidant properties, antifungal activity against dermatophytes and wound healing effect in skin cells. Overall, our results support the interest and economic value of two extracts obtained from a Portuguese native species and provide scientific validation to some of its traditional uses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114146DOI Listing
August 2021

Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

Clin Transl Allergy 2021 Mar;11(1):e12001

Servicio de Alergología, Departamento de Inmunología, Instituto de Investigación Sanitaria (IIS) Fundación Jiménez Díaz, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.

Introduction: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder.

Material And Methods: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients.

Results: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis.

Conclusion: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clt2.12001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173588PMC
March 2021

Third-Year Medical Students' Self-perceived Knowledge About Health Disparities and Community Medicine.

PRiMER 2021 25;5. Epub 2021 Feb 25.

Department of Family and Community Medicine, Thomas Jefferson University, Philadelphia, PA.

Introduction: Medical providers' attitudes about caring for vulnerable populations have significant implications for persistent health disparities. Therefore, assessing medical students' self-perceived knowledge about community-based medicine and care for underserved populations can provide insights for improving health care delivery to achieve health equity. We evaluated third-year medical students' perceptions of their knowledge and attitudes about community medicine, and addressing health care needs of vulnerable populations.

Methods: From October 2, 2017 to July 12, 2019, third-year medical students at a private, urban medical school were asked to complete an assessment survey during their family medicine clerkship orientation. The anonymous survey assessed students' self-perceived knowledge and attitudes regarding community medicine and care of vulnerable populations. We examined differences in survey responses by student demographics.

Results: A total of 401 students participated in the survey; 50.5% of respondents agreed that they had knowledge to assess health literacy of the patient, while only 22.2% of students agreed that they had knowledge about how to identify a community and conduct a community health needs assessment. Additionally, students agreed with being most comfortable providing care to adolescents (73.0%) and the elderly (69.5%), and that they were least comfortable caring for incarcerated individuals (31.7%) and immigrants/refugees (44.1%).

Conclusion: Assessment of learners' self-perceived knowledge can help highlight areas for educational interventions. Our findings suggest the need for improving medical student knowledge in areas of community health and health care for specific vulnerable populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22454/PRiMER.2021.235605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041226PMC
February 2021

Serum anti-Müllerian hormone levels are not associated with aneuploidy rates in human blastocysts.

Reprod Biomed Online 2021 Jun 15;42(6):1211-1218. Epub 2021 Mar 15.

IVI RMA Madrid, Av del Talgo 68, Madrid 28035, Spain; Rey Juan Carlos University, Madrid, Spain. Electronic address:

Research Question: Anti-Müllerian hormone (AMH) is the most established biomarker for estimating ovarian reserve. No reliable marker of oocyte quality, however, is available. Is there an association between the rates of aneuploidy and the different ranges of serum AMH levels?

Design: Retrospective, single-centre study of 1718 patients undergoing intracytoplasmic sperm injection and preimplantation genetic testing with aneuploidy at the blastocyst stage between January 2015 and December 2019. Patients were stratified into six different categories of AMH (ng/ml) according to percentile distribution.

Results: Although a higher number of biopsied embryos were found for higher AMH levels (P = 0.017), a lower rate of biopsied blastocysts per metaphase II (P = 0.019) and per fertilized oocyte (0.023) was observed in this group of high AMH. A higher number of euploid embryos was found for higher AMH values (P = 0.031); however, the rate of aneuploid embryos per metaphase II or per fertilized oocyte was not significantly different across the six groups. No differences were observed in the implantation, pregnancy and ongoing pregnancy rate, or in the miscarriage and biochemical loss rate. Regression analysis did not show any significant correlation between AMH and aneuploid embryos.

Conclusions: In this large series of patients, AMH was not related to embryo aneuploidy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2021.03.006DOI Listing
June 2021

A Commentary about Lessons Learned: Transitioning a Therapy Dog Program Online during the COVID-19 Pandemic.

Animals (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Sociology, University of Saskatchewan, Saskatoon, SK S7N 5A5, Canada.

In 2015, the University of Saskatchewan PAWS Your Stress Therapy Dog program partnered with St. John Ambulance for therapy dog teams to visit our campus and offer attendees love, comfort and support. We recognized at the start of the COVID-19 pandemic that students, staff and faculty may require mental health support, particularly with the challenges of isolation and loneliness. In response, our team transitioned from an in-person to a novel online format at the start of the COVID-19 pandemic. We designed online content for participants to (1) connect with therapy dogs and experience feelings of love, comfort and support as occurred in in-person programming, and (2) learn about pandemic-specific, evidence-informed mental health knowledge. Our unique approach highlighted what dogs can teach humans about health through their own care and daily activities. From April to June 2020, we developed a website, created 28 Facebook livestreams and 60 pre-recorded videos which featured therapy dogs and handlers, and cross-promoted on various social media platforms. Over three months, first a combined process-outcome evaluation helped us determine whether our activities contributed to the program's goals. A subsequent needs assessment allowed us to elicit participant preferences for the program moving forward. This commentary reflects on these findings and our teams' collective experiences to share our key lessons learned related to program personnel needs, therapy dog handler training and support requirements, and online programming prerequisites. This combined understanding is informing our current activities with the virtual program and should be of interest to other therapy dog programs transitioning online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani11030914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004773PMC
March 2021

Propolis from southeastern Brazil produced by Apis mellifera affects innate immunity by modulating cell marker expression, cytokine production and intracellular pathways in human monocytes.

J Pharm Pharmacol 2021 Mar;73(2):135-144

Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.

Objectives: Propolis is a bee-made product used for centuries due to its diverse biological properties, including its immunomodulatory action. This work aimed at investigating whether propolis may affect monocyte functions challenged with retinoic acid (RA), B subunit of Escherichia coli heat-labile enterotoxin (EtxB), human melanoma-associated antigen-1 (MAGE-1) and lipopolysaccharide (LPS).

Methods: Monocytes from healthy donors were treated with the stimuli separately or in the presence of propolis. Cell viability was evaluated by MTT assay, cell marker expression was assessed by flow cytometry, cytokine production by ELISA, gene expression by RT-qPCR.

Key Findings: Propolis alone maintained TLR-2, TLR-4, HLA-DR, CD40 and CD80 expression in the monocytes; however, its combination with either MAGE-1 or LPS decreased CD40 expression triggered by the stimuli. Propolis maintained RA action on cell marker expression. Propolis inhibited TNF-α (with either EtxB or MAGE-1) and IL-6 (with either RA or MAGE-1), and increased IL-10 (with MAGE-1) production. Propolis downmodulated LC3 expression induced by LPS. It also induced a lower NF-kB expression than control cells and its combination with RA induced a higher expression than the stimulus alone.

Conclusions: Propolis potentially affected innate immunity by downmodulating the monocytes pro-inflammatory activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpp/rgaa023DOI Listing
March 2021

Pilot Study Using Recombinant Antigens r-PROE and r-IGLL1 for the Serodiagnosis of Feather Duvet Lung.

Arch Bronconeumol (Engl Ed) 2021 Mar 4. Epub 2021 Mar 4.

Pulmonology Department, Hospital Universitari Vall d'Hebron, and VHIR, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Spain; CIBER enfermedades respiratorias (CIBERES), Catalonia, Spain.

Background: Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL).

Methods: Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15).

Results: The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms.

Conclusions: The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arbres.2021.02.011DOI Listing
March 2021

Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma.

Transfusion 2021 Jun 22;61(6):1705-1709. Epub 2021 Mar 22.

Grifols Bioscience Industrial Group, Research Triangle Park, North Carolina, USA.

Background: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG).

Study Design And Methods: Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases.

Results: Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels.

Conclusions: Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16378DOI Listing
June 2021

In-Depth Analysis of the Impact of Different Serum-Free Media on the Production of Clinical Grade Dendritic Cells for Cancer Immunotherapy.

Front Immunol 2020 5;11:593363. Epub 2021 Feb 5.

Department of Medical Sciences and Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.

Dendritic cell (DC)-based antitumor vaccines have proven to be a safe approach, but often fail to generate robust results between trials. Translation to the clinic has been hindered in part by the lack of standard operation procedures for vaccines production, namely the definition of optimal culture conditions during DC differentiation. Here we sought to compare the ability of three clinical grade serum-free media, DendriMACS, AIM-V, and X-VIVO 15, alongside with fetal bovine serum-supplemented Roswell Park Memorial Institute Medium (RPMI), to support the differentiation of monocyte-derived DCs (Mo-DCs). Under these different culture conditions, phenotype, cell metabolomic profiles, response to maturation stimuli, cytokines production, allogenic T cell stimulatory capacity, as well as priming of antigen-specific CD8 T cells and activation of autologous natural killer (NK) cells were analyzed. Immature Mo-DCs differentiated in AIM-V or X-VIVO 15 presented lower levels of CD1c, CD1a, and higher expression of CD11c, when compared to cells obtained with DendriMACS. Upon stimulation, only AIM-V or X-VIVO 15 DCs acquired a full mature phenotype, which supports their enhanced capacity to polarize T helper cell type 1 subset, to prime antigen-specific CD8 T cells and to activate NK cells. CD8 T cells and NK cells resulting from co-culture with AIM-V or X-VIVO 15 DCs also showed superior cytolytic activity. 1H nuclear magnetic resonance-based metabolomic analysis revealed that superior DC immunostimulatory capacities correlate with an enhanced catabolism of amino acids and glucose. Overall, our data highlight the impact of critically defining the culture medium used in the production of DCs for clinical application in cancer immunotherapy. Moreover, the manipulation of metabolic state during differentiation could be envisaged as a strategy to enhance desired cell characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.593363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893095PMC
February 2021

Structure of the parotid gland in natural infection by Leishmania infantum in Canis familiaris.

Arch Oral Biol 2021 Apr 11;124:105077. Epub 2021 Feb 11.

Master Program in Science and Health, Universidade Federal do Piauí, Campus Ministro Petrônio Portella, CEP: 64059-550, Teresina, Piauí, Brazil.

Objective: The objective of this study was to perform a histopathological, morphometric and proteomic study of the parotid gland of dogs naturally infected with Leishmania infantum treated and not treated with Allopurinol.

Design: Parotid glands from 14 dogs were used, divided into two groups: untreated and treated with oral allopurinol (20 mg / kg, once daily for 90 days). After adequate dissection, the organs were submitted to histopathological, histomorphometric and immunohistochemical techniques, using the monoclonal anti-β-catenin antibody.

Results: Histopathological evaluation of treated and untreated groups showed acinar hypertrophy, structural disorganization of the nucleus and cytoplasm. There was an increase in the area and perimeter of the parotid acini in the experimental groups. The immunostaining of the β-catenin protein in the membrane was severely reduced in the treated and untreated groups.

Conclusions: These findings suggest that Leishmania infantum infection and treatment with Allopurinol alter the tissue structure of the parotid gland in dogs, promoting an increase in the acinar volume and a decrease in the expression of β-catenin in cell membranes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2021.105077DOI Listing
April 2021

Role of Coffee Caffeine and Chlorogenic Acids Adsorption to Polysaccharides with Impact on Brew Immunomodulation Effects.

Foods 2021 Feb 9;10(2). Epub 2021 Feb 9.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

Coffee brews have High Molecular Weight (HMW) compounds with described immunostimulatory activity, namely polysaccharides and melanoidins. Melanoidins are formed during roasting and are modified during brews technological processing. In addition, brews have Low Molecular Weight (LMW) compounds, namely free chlorogenic acids and caffeine, with well-known anti-inflammatory properties. However, this study shows that both espresso and instant coffee brews did not present immunostimulatory neither anti-inflammatory in vitro activities. It is possible that the simultaneous existence of compounds with antagonistic effects can mitigate their individual effects. To test this hypothesis, an ultrafiltration separation process was applied, studying the behavior of coffee brews' HMW on retention of LMW compounds. Several ultrafiltration sequential cycles were required to separate retentates from LMW compounds, suggesting their retention. This effect was higher in instant coffee, attributed to its initial higher carbohydrate content when compared to espresso. Separation of HMW and LMW compounds boosted their immunostimulatory (6.2-7.8 µM nitrites) and anti-inflammatory (LPS induced nitrite production decrease by 36-31%) in vitro activities, respectively. As coffee anti-inflammatory compounds are expected to be first absorbed during digestion, a potential in vivo fractionation of LMW and HMW compounds can promote health relevant effects after coffee intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods10020378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916192PMC
February 2021

Therapies for Alzheimer's disease: a metabolic perspective.

Mol Genet Metab 2021 03 27;132(3):162-172. Epub 2021 Jan 27.

Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra 3000-548, Portugal. Electronic address:

Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly. Currently, there are over 50 million cases of dementia worldwide and it is expected that it will reach 136 million by 2050. AD is described as a neurodegenerative disease that gradually compromises memory and learning capacity. Patients often exhibit brain glucose hypometabolism and are more susceptible to develop type 2 diabetes or insulin resistance in comparison with age-matched controls. This suggests that there is a link between both pathologies. Glucose metabolism and the tricarboxylic acid cycle are tightly related to mitochondrial performance and energy production. Impairment of both these pathways can evoke oxidative damage on mitochondria and key proteins linked to several hallmarks of AD. Glycation is also another type of post-translational modification often reported in AD, which might impair the function of proteins that participate in metabolic pathways thought to be involved in this illness. Despite needing further research, therapies based on insulin treatment, usage of anti-diabetes drugs or some form of dietary intervention, have shown to be promising therapeutic approaches for AD in its early stages of progression and will be unveiled in this paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2021.01.011DOI Listing
March 2021

Early Pregnancy Outcomes in Fresh Versus Deferred Embryo Transfer Cycles for Endometriosis-Associated Infertility: A Retrospective Cohort Study.

J Clin Med 2021 Jan 18;10(2). Epub 2021 Jan 18.

IVI-RMA, 28023 Madrid, Spain.

Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists regarding the mechanism of endometriosis-associated infertility and benefits of deferred ET on endometrial receptivity. Hence, the purpose of this study was to compare in vitro fertilization (IVF) outcomes in women with endometriosis, diagnosed by histology, undergoing fresh versus deferred-ET after elective cryopreservation. Of the 728 women included, no significant differences were observed in baseline patient characteristics and response to gonadotrophin stimulation between fresh and deferred ET groups. Furthermore, no significant differences in implantation rate (49.7 vs. 49.9%, = 0.73), clinical pregnancy rate (40.9 vs. 39.9%, = 0.49), and miscarriage rate (9.4 vs. 9.9%, = 0.63) were observed between fresh and deferred ET groups, respectively. Hence, contrary to previous studies, our results suggest that a deferred ET "freeze-all" IVF strategy does not improve early pregnancy outcomes among women with endometriosis. However, prospective studies are required to validate these findings and further insight into the etiology and pathogenesis of endometriosis-associated infertility are necessary to optimize IVF protocols in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10020344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831308PMC
January 2021

Lifetime employment in schizophrenia: correlates of developing long term unemployment after being employed before.

Cogn Neuropsychiatry 2021 03 30;26(2):95-106. Epub 2020 Dec 30.

Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.

Background: Challenges in employment are highly prevalent among people with schizophrenia regardless of their employment history. Although supportive employment can be effective, few participants sustain meaningful competitive employment. Our goal was to identify the correlates of developing sustained unemployment.

Methods: We examined employment outcomes by comparing clinical, neurocognitive, and social cognitive features in 234 participants with Schizophrenia Spectrum Disorders across t competitive employment outcomes: currently employed, participants who had never worked for a year, and those who had been employed but developed long-term unemployment. We examined social cognition and neurocognition, as well as positive and negative schizophrenia symptoms, and premorbid functioning and demographic factors.

Results: We found significant differences in age, race, premorbid functioning, cognitive performance, and social cognition between currently and formerly employed patients. When individual tasks were examined, emotion recognition and verbal working memory performance were the domains differentiating the groups. Older African Americans were over-represented in the formerly employed group.

Conclusions: There were minimal differences other than age and race between formerly employed patients and those who had never worked. These data suggest the possibility that deterioration in employment outcomes may also co-occur with declines in other abilities. Opportunities and disparities may also be a contributor to re-entering the work force.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13546805.2020.1865896DOI Listing
March 2021

L. subsp. Leaves: Nutritional Profile, Phenolic Composition and Biological Properties.

Int J Environ Res Public Health 2020 12 28;18(1). Epub 2020 Dec 28.

Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.

subsp. (Cv) of Asteraceae family is used as food and in traditional medicine. However there are no studies on its nutritional value, phenolic composition and biological activities. In the present work, a nutritional analysis of Cv leaves was performed and its phenolic content and biological properties evaluated. The nutritional profile was achieved by gas chromatography (GC). A 70% ethanolic extract was prepared and characterized by HLPC-PDA-ESI/MS. The quantification of chicoric acid was determined by HPLC-PDA. Subsequently, it was evaluated its antioxidant activity by DPPH, ABTS and FRAP methods. The anti-inflammatory activity and cellular viability was assessed in Raw 264.7 macrophages. On wet weight basis, carbohydrates were the most abundant macronutrients (9.99%), followed by minerals (2.74%) (mainly K, Ca and Na), protein (1.04%) and lipids (0.69%), with a low energetic contribution (175.19 KJ/100 g). The Cv extract is constituted essentially by phenolic acids as caffeic, ferulic and quinic acid derivatives being the major phenolic constituent chicoric acid (130.5 mg/g extract). The extract exhibited antioxidant activity in DPPH, ABTS and FRAP assays and inhibited the nitric oxide (NO) production induced by LPS (IC = 0.428 ± 0.007 mg/mL) without cytotoxicity at all concentrations tested. Conclusions: Given the nutritional and phenolic profile and antioxidant and anti-inflammatory properties, Cv could be a promising useful source of functional food ingredients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18010151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796387PMC
December 2020

Magnetic-Activated Cell Sorting (MACS): A Useful Sperm-Selection Technique in Cases of High Levels of Sperm DNA Fragmentation.

J Clin Med 2020 Dec 8;9(12). Epub 2020 Dec 8.

IVI Madrid, 28023 Madrid, Spain.

Magnetic-activated cell sorting (MACS) can be used to separate apoptotic sperm with high proportions of fragmented DNA from the rest, thus improving the overall quality of the seminal sample. Therefore, the aim of this retrospective study was to investigate the efficiency of the MACS technique to increase reproductive outcomes in patients with high levels of sperm DNA fragmentation (SDF) undergoing intracytoplasmic sperm-injection (ICSI) cycles. In this study, we analyzed a total of 724 assisted-reproduction-technique (ART) cycles that were divided into two groups: the study group ( = 366) in which the MACS selection technique was performed after density-gradient centrifugation (DGC), and the control group ( = 358) in which only DGC was used for sperm selection. Reproductive outcomes were analyzed in both groups according to three different ART procedures: preimplantation genetic testing for aneuploidy (PGT-A), and autologous and oocyte-donation cycles. The MACS group showed significantly lower miscarriage rates in autologous ICSI cycles, higher pregnancy rates in oocyte-donation cycles, and a significant increase in live-birth rates in both autologous and oocyte-donation cycles. Overall, these results suggested that the MACS technique can be effectively used to eliminate sperm with high SDF levels, and therefore may help to improve reproductive outcomes in couples undergoing ART.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9123976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763893PMC
December 2020

Inflammation in Bipolar Disorder (BD): Identification of new therapeutic targets.

Pharmacol Res 2021 01 2;163:105325. Epub 2020 Dec 2.

University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Center for Neuroscience and Cell Biology (CNC), 3004-504, Coimbra, Portugal; University of Coimbra, Faculty of Pharmacy, 3000-548, Coimbra, Portugal. Electronic address:

Bipolar disorder (BD) is a chronic and cyclic mental disorder, characterized by unusual mood swings between mania/hypomania and depression, raising concern in both scientific and medical communities due to its deleterious social and economic impact. Polypharmacy is the rule due to the partial effectiveness of available drugs. Disease course is often unremitting, resulting in frequent cognitive deficits over time. Despite all research efforts in identifying BD-associated molecular mechanisms, current knowledge remains limited. However, the involvement of inflammation in BD pathophysiology is increasingly consensual, with the immune system and neuroinflammation playing a key role in disease course. Evidence includes altered levels of cytokines and acute-phase proteins, pathological microglial activation, deregulation of Nrf2-Keap1 system and changes in biogenic amines neurotransmitters, whose expression is regulated by TNF-α, a pro-inflammatory cytokine highly involved in BD, pointing out inflammation as a novel and attractive therapeutic target for BD. As result, new therapeutic agents including non-steroidal anti-inflammatory drugs, N-acetylcysteine and GSK3 inhibitors have been incorporated in BD treatment. Taking into consideration the latest pre-clinical and clinical trials, in this review we discuss recent data regarding inflammation in BD, unveiling potential therapeutic approaches through direct or indirect modulation of inflammatory response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105325DOI Listing
January 2021

Pharmacological combination of nivolumab with dendritic cell vaccines in cancer immunotherapy: An overview.

Pharmacol Res 2021 02 16;164:105309. Epub 2020 Nov 16.

Department of Medical Sciences and Institute of Biomedicine, iBiMED, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address:

In the last decade, immunotherapy led to a paradigm shift in the treatment of numerous malignancies. Alongside with monoclonal antibodies blocking programmed cell death receptor-1 (PD-1)/PD-L1 and cytotoxic T- lymphocyte antigen 4 (CTLA-4) immune checkpoints, cell-based approaches such as CAR-T cells and dendritic cell (DC) vaccines have strongly contributed to pushing forward this thrilling field. While initial strategies were mainly focused on monotherapeutic regimens, it is now consensual that the combination of immunotherapies tackling multiple cancer hallmarks can result in superior clinical outcomes. Here, we review in depth the pharmacological combination of DC-based vaccines that boost tumour elimination by eliciting and expanding effector immune cells, with the PD-1 inhibitor Nivolumab that allows blocking key tumour immune escape mechanisms. This combination represents an important step in cancer therapy, with a significant enhancement in patient survival in several types of tumours, paving an important way in establishing combinatorial immunotherapeutic strategies as first-line treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105309DOI Listing
February 2021

Enhancement of infectivity of insect cell-derived La Crosse Virus by human serum.

Virus Res 2021 01 11;292:198228. Epub 2020 Nov 11.

University of Central Florida, College of Medicine, Orlando, FL, 32827, United States. Electronic address:

Given the dual life cycle of arboviruses in insect and animal hosts and the importance of serum factors as a first line antiviral defense, we have examined the outcome of interactions between the arbovirus La Crosse Virus (LACV) and human serum. To mimic the life cycle between species, we used LACV derived from insect (I-LACV) and human keratinocyte (HaCaT) cells. Incubation of I-LACV with normal human serum did not result in neutralization, but instead stabilized I-LACV virions and enhanced the amount of infectious virus. Enhanced infectivity was also seen with heat-inactivated serum devoid of complement activity and with serum from a range of animals including mouse, ferret, and non-human primates. Depletion of antibodies from serum resulted in loss of enhancement of infectivity and sucrose gradient sedimentation assays showed IgG co-sedimenting with I-LACV particles. In agreement with our results with I-LACV, HaCaT-derived LACV was not neutralized by complement or antibodies in normal human serum. However, in contrast to I-LACV, HaCaT-derived LACV infectivity was stable when incubated alone and treatment with serum did not enhance infectivity. Our results indicate that LACV derived from insect cells differs substantially from virus derived from human cells, with I-LACV being dependent on serum factors to enhance infectivity. These findings suggest that understanding differential composition of insect versus animal cell-derived LACV may form the foundation for potential new antiviral approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2020.198228DOI Listing
January 2021

Assessment and Management of Occupational Hypersensitivity Pneumonitis.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3295-3309

Servei de Pneumologia, Vall d´Hebron Institut de Recerca (VHIR), Barcelona, Spain; Instituto de Salud Carlos III, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.

The diagnosis and treatment of occupational hypersensitivity pneumonitis (OHP) remain complex and challenging in the absence of diagnostic gold standards or clinical guidelines. This review provides an update of the recent literature regarding the different presentations of OHP and the diagnostic yield and value of the diagnostic tests currently available, which include occupational and medical history, laboratory tests (serum-specific immunoglobulins, environmental sampling), imaging, bronchoalveolar lavage, transbronchial biopsy, transbronchial cryobiopsy, surgical lung biopsy, and specific inhalation challenges. These tools provide a precise differential diagnosis within the framework of interstitial lung diseases. However, among the chronic fibrotic forms, distinguishing OHP from sarcoidosis, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis remains a diagnostic challenge. Avoidance of exposure is pivotal for OHP management, whereas corticosteroids are fundamental in the pharmacological approach to this disease. In addition, studies describing the long-term benefits of immunosuppressive and antifibrotic agents have increased the use of these treatments in OHP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.09.002DOI Listing
May 2021

Allergic contact dermatitis: From pathophysiology to development of new preventive strategies.

Pharmacol Res 2020 12 5;162:105282. Epub 2020 Nov 5.

Faculty of Pharmacy, University of Coimbra, Coimbra, 3000-548, Portugal; Center for Neuroscience and Cell Biology - CNC, University of Coimbra, Coimbra, 3004-504, Portugal. Electronic address:

As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a significant public health burden. Among skin disorders, allergic contact dermatitis (ACD) is the most prevalent occupational disease and the most common form of immunotoxicity in humans. ACD is a T-cell-mediated skin inflammation resulting from the priming and expansion of allergen-specific CD4 and CD8 T cells. The clinical condition is characterized by local skin rash, itchiness, redness, swelling, and lesions, being mainly diagnosed by the patch test. Upon ACD diagnosis, avoiding the exposure to the triggering allergen is the mainstay of treatment to prevent future flares. In cases where avoidance is not possible, the use of a standard of care interim treatments such as steroid creams or ointments, barrier creams, and moisturizers are strongly recommended to alleviate symptoms. In this review, we sought to provide the reader with an overview of the pathophysiology of ACD as well as the currently available pharmacological treatment options. Furthermore, a comprehensive outline of several preventive strategies is also provided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105282DOI Listing
December 2020

Diagnosis of pulmonary tuberculosis in children and adolescents: comparison of two versions of the Brazilian Ministry of Health scoring system.

Rev Inst Med Trop Sao Paulo 2020 30;62:e81. Epub 2020 Oct 30.

Universidade Federal do Rio de Janeiro , Rio de Janeiro , Rio de Janeiro , Brazil.

The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/S1678-9946202062081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608063PMC
January 2021

Antifungal and anti-inflammatory potential of the endangered aromatic plant Thymus albicans.

Sci Rep 2020 11 2;10(1):18859. Epub 2020 Nov 2.

Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal.

Thymus albicans is an endemic species of the Iberian Peninsula with a vulnerable conservation status. In an attempt to contribute to the valorization of this species, the present study brings new insights on the antifungal and anti-inflammatory mechanism of action of T. albicans essential oil. The antifungal activity of the oil and its major compounds was assessed for the first time against standard and clinically isolated strains of yeasts and filamentous fungi. The effect on the two major virulence factors of Candida albicans (germ tube formation and biofilm disruption) was considered in more detail. At 0.08 μL/mL, the oil inhibited C. albicans germ tube formation by more than 40% and decreased biofilm biomass at MIC values, thus pointing out its antivirulent potential. The anti-inflammatory activity of the essential oil was investigated on LPS-stimulated mouse macrophages (RAW 264.7) by evaluating the levels of several pro-inflammatory mediators, namely nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). T. albicans oil reduced the production of nitrites, a NO derived sub-product, at non-cytotoxic concentrations of 0.32 and 0.64 μL/mL, by 27 and 41%, respectively. In addition, the iNOS protein levels of essential oil pre-treated cells were reduced by 14%. Overall, the high essential oil yield of T. albicans as well as its bioactive effects at concentrations without cytotoxicity, encourage further studies on the potential pharmacological applications of this species. Furthermore, these results raise awareness for the need to preserve endangered species that may hold relevant medicinal value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-75244-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608662PMC
November 2020

Effects of explaining system failures during maneuver coordination while driving manual or automated.

Accid Anal Prev 2020 Dec 23;148:105839. Epub 2020 Oct 23.

Würzburg Institute for Traffic Sciences (WIVW), Robert-Bosch-Straße 4, 97209, Veitshöchheim, Germany. Electronic address:

To support the coordination of road users in situations like merging or turning left, an advanced driver assistance system for cooperative driving could be helpful whether driving manually or automated. This simulator study investigated the behavior of drivers being confronted with system failures. In two test situations with system failures (loss of communication of the system and change of traffic environment), the system could not complete the coordination properly and the driver was informed about the system failure and the abortion of maneuver coordination. The focus of this study was to analyze the effect of system failures on drivers' trust in the system and whether an explanatory message provided by the system would increase acceptance. Therefore, subjective data as well as gaze and physiological data of 32 participants were analyzed. The results revealed decreased trust in the system after experiencing a system failure, but no long term effect was found. The drivers evaluated the timing, as well as the content, of the explanatory message as appropriate. The explanations were perceived as helpful, but no effect on acceptance was found.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aap.2020.105839DOI Listing
December 2020

Calcium Modulation, Anti-Oxidant and Anti-Inflammatory Effect of Skin Allergens Targeting the Nrf2 Signaling Pathway in Alzheimer's Disease Cellular Models.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Center for Neuroscience and Cell Biology and Institute for Biomedical Imaging and Life Sciences, University of Coimbra, 3000-548 Coimbra, Portugal.

Experimental evidence highlights nuclear factor (erythroid-derived 2)-like 2 (Nrf2) as a molecular target in Alzheimer's disease (AD). The well-known effect of electrophilic cysteine-reactive skin allergens on Nrf2-activation led to the hypothesis that these compounds could have a therapeutic role in AD. This was further supported by the neuroprotective activity of the skin allergen dimethyl fumarate (DMF), demonstrated in in vivo models of neurodegenerative diseases. We evaluated the effect of the cysteine-reactive allergens 1,4-phenylenediamine (PPD) and methyl heptine carbonate (MHC) on (1) neuronal redox imbalance and calcium dyshomeostasis using N2a wild-type (N2a-wt) and human APP-overexpressing neuronal cells (wild-type, N2a-APPwt) and (2) on neuroinflammation, using microglia BV-2 cells exposed to LPS (lipopolysaccharide). Phthalic anhydride (PA, mainly lysine-reactive), was used as a negative control. DMF, PPD and MHC increased Hmox1 gene and HMOX1 protein levels in N2a-APPwt cells suggesting Nrf2-dependent antioxidant activity. MHC, but also PA, rescued N2a-APPwt mitochondrial membrane potential and calcium levels in a Nrf2-independent pathway. All the chemicals showed anti-inflammatory activity by decreasing iNOS protein in microglia. This work highlights the potential neuroprotective and anti-inflammatory role of the selected skin allergens in in vitro models of AD, and supports further studies envisaging the validation of the results using in vivo AD models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21207791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594024PMC
October 2020

Phlorotannins from : Modulation of Inflammatory Response by Blocking NF-κB Signaling Pathway.

Int J Mol Sci 2020 Sep 20;21(18). Epub 2020 Sep 20.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

Due to their large spectrum of bioactive properties, much attention has recently been drawn to phlorotannins-i.e., phenolic compounds characteristic from brown macroalgae. This study aimed to evaluate the antioxidant and anti-inflammatory properties of phlorotannin extracts and purified fractions. Overall, the crude extract and its ethyl acetate fraction (EtOAc) showed good radical scavenging activity, particularly towards nitric oxide (NO). Subsequent subfractions of EtOAc (F1 to F9) with different molecular weights were then shown to inhibit lipopolysaccharide-induced NO production in macrophages, with stronger effects being observed for fractions of lower MWs. Of the three intracellular markers analyzed, inducible NO synthase showed the highest sensitivity to almost all the phlorotannin-rich samples, followed by interleukin 1β and cyclooxygenase 2, which was only inhibited by F2. Furthermore, this subfraction inhibited the phosphorylation and degradation of inhibitory protein κBα, thus preventing the activation of NF-κB and blocking the inflammatory cascade at the transcriptional level. This sample was characterized by the presence of a major compound with a deprotonated molecular ion at 507 with a fragmentation pattern coherent with that of a phlorotannin derivative. Overall, this work unveiled some of the mechanistic aspects behind the anti-inflammatory capacity of phlorotannins from , endorsing its use as a possible natural source of anti-inflammatory compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21186897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554702PMC
September 2020