Publications by authors named "M Carmen Alonso"

2,331 Publications

  • Page 1 of 1

Immune cells fold and damage fungal hyphae.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Aberdeen Fungal Group, Institute of Medical Sciences, Foresterhill, AB25 2ZD Aberdeen, United Kingdom;

Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of -macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin-myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.
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http://dx.doi.org/10.1073/pnas.2020484118DOI Listing
April 2021

Socioeconomic and demographic factors associated with failure in eradication using the standard triple therapy.

Gastroenterol Hepatol Bed Bench 2021 ;14(1):53-58

Aragón Health Research Institute (IIS Aragón), Spain.

Aim: To evaluate the influence of socioeconomic and demographic factors on the eradication rate of , using standard triple therapy.

Background: the efficacy of the standard triple therapy (STT) for eradication has decreased with the rise of antibiotic resistance. Other factors could influence the eradication failure, although available results are conflicting.

Methods: Retrospective study, including adults with infection treated de novo with STT (proton pump inhibitor, amoxicillin and clarithromycin). Eradication success was assessed by C-urea breath test. Demographic and socioeconomics variables were evaluated and correlated with eradication treatment outcome. The confounder variables were controlled by logistic regression analysis.

Results: Out of 902 patients with diagnosis, 693 met inclusion criteria (average age 53 years; females 55.2%). Non-significant differences were observed in relation to economics income between rural and urban areas (p=0.316). The eradication rate of was 71.1%: male 78.9% vs female 65.9%, urban area 73.4% vs rural area 64.1%. With reference to age, income and nationality, the eradication rates were similar in all groups. According to logistic regression analysis, females had almost twice more likelihood of eradication failure in relation to males (OR 1.92; 95%CI: 1.38-2.72); and rural residents had OR 1.55 (95%CI: 1.03-2.33) for having eradication failure in contrast with urban population.

Conclusion: Female gender and rural residence are factors associated with H. Pylori eradication failure with standard triple therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035545PMC
January 2021

TRAINING AND PANDEMIC.

Rev Esp Cir Ortop Traumatol 2021 May-Jun;65(3):165-166

Presidente de la Comisión Nacional de la Especialidad de Traumatología y Cirugía Ortopédica. Electronic address:

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http://dx.doi.org/10.1016/j.recot.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045448PMC
April 2021

Genetically determined telomere length and multiple myeloma risk and outcome.

Blood Cancer J 2021 Apr 14;11(4):74. Epub 2021 Apr 14.

Department of Biology, University of Pisa, Pisa, Italy.

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 × 10 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.
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http://dx.doi.org/10.1038/s41408-021-00462-yDOI Listing
April 2021

Ibero-Panamerican Federation of Periodontics Delphi study on the trends in Diagnosis and Treatment of Peri-implant Diseases and Conditions: A Latin American consensus.

J Periodontol 2021 Apr 14. Epub 2021 Apr 14.

ETEP (Etiology and Therapy of Periodontal and Peri-Implant Diseases) Research Group, University Complutense.

Background: The social diversity, heterogeneous culture and inherent economic inequality factors in Latin America (LA) justify conducting a comprehensive analysis on the current status and future trends of peri-implant diseases and conditions. Thus, the aim of this Delphi study was to predict the future trends in the diagnosis and treatment of peri-implant diseases and conditions in LA countries for the year 2030.

Materials And Methods: A Latin American steering committee and group of experts in implant dentistry validated a questionnaire including 64 questions divided into 8 sections. The questionnaire was run twice with an interval of 45 days, with the results from the first round made available to all the participants in the second round. The results were expressed in percentages and data was analyzed describing the consensus level reached in each question.

Results: 221 experts were invited to participate in the study and a total 214 (96.8%) completed the two rounds. Moderate (65%-85%) to high consensus (≥85%) was reached in 51 questions (79.69%), except in the questions dealing with "prevalence", where no consensus was reached. High and moderate consensus was attained for all the questions in three fields (risk factors and indicators, diagnosis and treatment of peri-implant conditions and deficiencies, and prevention and maintenance).

Conclusions: The present study has provided relevant and useful information on the predictions in the diagnosis and treatment of peri-implant diseases with a high level of consensus among experts. Nevertheless, there is still a lack of agreement in certain domains. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/JPER.21-0086DOI Listing
April 2021

Cold-Shock Test Is a Practical Method for Selecting Boar Ejaculates Yielding Appropriate Seminal Plasma for Post-Thawing Supplementation.

Animals (Basel) 2021 Mar 18;11(3). Epub 2021 Mar 18.

Institute of Animal Health and Cattle Development (INDEGSAL), Universidad de León, 24071 León, Spain.

Artificial insemination (AI) with cryopreserved semen is still unreliable for extensive pig industry application. Adding seminal plasma (SP) could improve post-thawing quality, but its suitability could vary. We applied a simple cold-shock test (CST, 5 min at 0 °C) on neat semen for classifying ejaculates ( = 63) as resistant or sensitive, obtaining two SP pools (CST-resistant: SPr, sensitive: SPs). Subsequently, frozen/thawed spermatozoa from six boars were incubated (37 °C) in MR-A® extender (control), 20% SPr, or 20% SPs, and analyzed at 0, 2, and 4 h. SP improved total and progressive motility, with a higher effect for SPr and STR ( < 0.05), decreasing kinematic parameters VCL and VAP, ALH, and BCF. Sperm viability was unaffected. SP increased apoptotic and membrane disorder ratios, and acrosomal damage, not affecting the chromatin structure (DNA fragmentation and immaturity by SCSA), protamination (CMA3), or disulfide levels (mBBr). However, the proportion of spermatozoa with elevated free thiols (disulfide bridges reduction) significantly increased. Results support a stimulatory role of SP on thawed semen, with additional benefits from SPr. The effect of SP and especially SPr after AI should be tested since CST could be a practical test for selecting suitable ejaculates in AI centers.
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http://dx.doi.org/10.3390/ani11030871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003138PMC
March 2021

Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression.

Int J Mol Sci 2021 Mar 6;22(5). Epub 2021 Mar 6.

Medical Oncology Department, Catalan Institute of Cancer (ICO), IDIBELL-OncoBell, Hospitalet de Llobregat, 08908 Barcelona, Spain.

Uveal melanoma (UM) is a malignant tumor that arises in the melanocytes of the uveal tract. It is the most frequent eye cancer, and despite new therapeutic approaches, prognosis is still poor, with up to 50% of patients developing metastasis with no efficient treatment options available. In contrast to cutaneous melanoma, UM is considered an "immune-cold" tumor due to the low mutational burden and the unique immunosuppressive microenvironment. To gain insight into the role of the UM microenvironment in regard to prognosis and metastatic progression, we have performed a pool analysis characterizing the UM microenvironment by using a bioinformatic approach. A variety of scores based on gene expression measuring stromal infiltration were calculated and used to assess association with prognosis. As a result, the highest immune and stromal scores were associated with poor prognosis. Specifically, stromal cells (fibroblasts and endothelial cells), T cells CD8+, natural killer (NK) cells, and macrophages M1 and M2 infiltration were associated with poor prognosis. Contrary to other tumors, lymphocytic infiltration is related to poor prognosis. Only B cells were associated with more favorable prognosis. UM samples scoring high in both angiogenesis (Angio) and antigen presentation (AP) pathways showed a poor prognosis suggesting an additive role of both functions. Almost all these tumors exhibited a chromosome 3 monosomy. Finally, an enrichment analysis showed that tumors classified as high Angio-high AP also activated metabolic pathways such as glycolysis or PI3K-AKT-MTOR. In summary, our pool analysis identified a cluster of samples with angiogenic and inflammatory phenotypes exhibiting poor prognosis and metabolic activation. Our analysis showed robust results replicated in a pool analysis merging different datasets from different analytic platforms.
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http://dx.doi.org/10.3390/ijms22052669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961481PMC
March 2021

Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery.

Drug Deliv Transl Res 2021 Apr 1. Epub 2021 Apr 1.

Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), School of Pharmacy, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.

In the last few decades, nanotechnology has emerged as an important tool aimed at enhancing the immune response against modern antigens. Nanocarriers designed specifically for this purpose have been shown to provide protection, stability, and controlled release properties to proteins, peptides, and polynucleotide-based antigens. Polysaccharides are particularly interesting biomaterials for the construction of these nanocarriers given their wide distribution among pathogens, which facilitates their recognition by antigen-presenting cells (APCs). In this work, we focused on an immunostimulant beta-glucan derivative, carboxymethyl-β-glucan, to prepare a novel nanocarrier in combination with chitosan. The resulting carboxymethyl-β-glucan/chitosan nanoparticles exhibited adequate physicochemical properties and an important protein association efficiency, with ovalbumin as a model compound. Moreover, thermostability was achieved through the optimization of a lyophilized form of the antigen-loaded nanoparticles, which remained stable for up to 1 month at 40 ºC. Biodistribution studies in mice showed an efficient drainage of the nanoparticles to the nearest lymph node following subcutaneous injection, and a significant co-localization with dendritic cells. Additionally, subcutaneous immunization of mice with a single dose of the ovalbumin-loaded nanoparticles led to induced T cell proliferation and antibody responses, comparable to those achieved with alum-adsorbed ovalbumin. These results illustrate the potential of these novel nanocarriers in vaccination.
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http://dx.doi.org/10.1007/s13346-021-00968-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015750PMC
April 2021

Current strategies to circumvent the antiviral immunity to optimize cancer virotherapy.

J Immunother Cancer 2021 Apr;9(4)

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Cancer virotherapy is a paradigm-shifting treatment modality based on virus-mediated oncolysis and subsequent antitumor immune responses. Clinical trials of currently available virotherapies showed that robust antitumor immunity characterizes the remarkable and long-term responses observed in a subset of patients. These data suggest that future therapies should incorporate strategies to maximize the immunotherapeutic potential of oncolytic viruses. In this review, we highlight the recent evidence that the antiviral immunity of the patients may limit the immunotherapeutic potential of oncolytic viruses and summarize the most relevant approaches to strategically redirect the immune response away from the viruses and toward tumors to heighten the clinical impact of viro-immunotherapy platforms.
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http://dx.doi.org/10.1136/jitc-2020-002086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021759PMC
April 2021

Serum reactive oxygen species and apoptosis markers in septic patients.

Anaesthesiol Intensive Ther 2021 Mar 31. Epub 2021 Mar 31.

Universidad de Buenos Aires, Facultad de Medicina, Departamento de Bioquímica Humana (INBIOMED UBA-CONICET), Argentina.

Introduction: Oxidative stress is one of the pathophysiological processes that occur during sepsis. Reactive oxygen species (ROS) production causes lipid peroxidation and protein and DNA damage. ROS and DNA damage triggers apoptosis. Several studies have shown that organ failure in sepsis is mediated by apoptosis. The aim of this study is to investigate the levels of serum ROS and serum caspase-3 in septic patients and healthy volunteers, and their correlation.

Material And Methods: Serum samples were taken within the first 12 hours of ICU stay. The dichlorofluorescein technique was used to determine serum ROS levels, and the ELISA technique was used to quantify serum caspase-3 in septic patients and healthy volunteers.

Results: There was no difference in serum ROS levels between healthy volunteers and septic patients (P = 0.26), and there was a significant difference in serum caspase-3 levels between healthy volunteers and septic patients (P < 0.001). There was no difference between patients who lived and died in the intensive care unit (ICU) in serum ROS (P = 0.089) and serum caspase-3 (P = 0.18). There was no correlation between both markers (R = -0.0013, P = 0.98).

Conclusions: We conclude that there is no correlation between serum ROS and caspase-3; therefore, both processes might not be associated during the first hours of ICU stay.
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http://dx.doi.org/10.5114/ait.2021.104360DOI Listing
March 2021

Mantenimiento de tratamientos crónicos en pacientes afectados de COVID-19.

FMC 2021 Mar 23;28(3):191-201. Epub 2021 Mar 23.

Médico de familia, Unidad de Investigación Gerencia de Atención Primaria, Madrid, España.

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http://dx.doi.org/10.1016/j.fmc.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984871PMC
March 2021

Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse.

Oncoimmunology 2021 Mar 9;10(1):1862529. Epub 2021 Mar 9.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AIC:238.1-238.9; CMS-AIC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance.
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http://dx.doi.org/10.1080/2162402X.2020.1862529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951964PMC
March 2021

Unnecessary Abdominal Surgeries in Attacks of Hereditary Angioedema with Normal C1 Inhibitor.

Clin Rev Allergy Immunol 2021 Mar 23. Epub 2021 Mar 23.

Faculdade de Medicina, Centro Universitario Saude ABC, Santo Andre, Sao Paulo, SP, Brazil.

Hereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a retrospective study where patients were diagnosed with recurrent angioedema without urticaria, normal C1-INH levels, and positive family history of angioedema. All patients were evaluated for the known mutations located at exon 9 of the F12 gene. Medical records were evaluated and questionnaires were applied to 52 patients with normal C1-INH levels (age range 13-76 years; 47/52, 90.38% women; 5/52, 9.61% men). F12 mutation was present in 32/52 patients (61.5%). Acute abdominal pain was diagnosed in 16/52 (30.76%) patients, appendicitis in 9/16 (56.2%), and undetermined diagnosis in 7/16 (43.7%). Among patients diagnosed with acute abdominal pain, 13/16 (81.2%) underwent surgery and 3/16 (18.7%) improved without surgical intervention. We conclude that many HAE patients with coagulation factor XII mutation were misdiagnosed with acute abdomen and subjected to unnecessary invasive procedures. It is critical to disseminate information about this rare mutation in patients with otherwise normal C1-INH activity, in order to speed up diagnosis and avoid misconduct.
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http://dx.doi.org/10.1007/s12016-021-08852-7DOI Listing
March 2021

Correction to: Asymmetric flow field‑flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers.

Drug Deliv Transl Res 2021 Apr;11(2):396

Center for Research in Molecular Medicine and Chronic Diseases, Singular Research Centers, 15782, Santiago de Compostela, Spain.

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http://dx.doi.org/10.1007/s13346-021-00962-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987704PMC
April 2021

Vascular and Macrophage Heme Oxygenase-1 in Hypertension: A Mini-Review.

Front Physiol 2021 26;12:643435. Epub 2021 Feb 26.

Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.

Hypertension is one predictive factor for stroke and heart ischemic disease. Nowadays, it is considered an inflammatory disease with elevated cytokine levels, oxidative stress, and infiltration of immune cells in several organs including heart, kidney, and vessels, which contribute to the hypertension-associated cardiovascular damage. Macrophages, the most abundant immune cells in tissues, have a high degree of plasticity that is manifested by polarization in different phenotypes, with the most well-known being M1 (proinflammatory) and M2 (anti-inflammatory). In hypertension, M1 phenotype predominates, producing inflammatory cytokines and oxidative stress, and mediating many mechanisms involved in the pathogenesis of this disease. The increase in the renin-angiotensin system and sympathetic activity contributes to the macrophage mobilization and to its polarization to the pro-inflammatory phenotype. Heme oxygenase-1 (HO-1), a phase II detoxification enzyme responsible for heme catabolism, is induced by oxidative stress, among others. HO-1 has been shown to protect against oxidative and inflammatory insults in hypertension, reducing end organ damage and blood pressure, not only by its expression at the vascular level, but also by shifting macrophages toward the anti-inflammatory phenotype. The regulatory role of heme availability for the synthesis of enzymes involved in hypertension development, such as cyclooxygenase or nitric oxide synthase, seems to be responsible for many of the beneficial HO-1 effects; additionally, the antioxidant, anti-inflammatory, antiapoptotic, and antiproliferative effects of the end products of its reaction, carbon monoxide, biliverdin/bilirubin, and Fe, would also contribute. In this review, we analyze the role of HO-1 in hypertensive pathology, focusing on its expression in macrophages.
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http://dx.doi.org/10.3389/fphys.2021.643435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952647PMC
February 2021

The Effectiveness of Dichloroacetate on Human Glioblastoma Xenograft Growth Depends on Na+ and Mg2+ Cations.

Dose Response 2021 Jan-Mar;19(1):1559325821990166. Epub 2021 Feb 27.

Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

The study's aim was to investigate the effectiveness of sodium dichloroacetate (NaDCA) or magnesium dichloroacetate (MgDCA) on adult U87 MG and pediatric PBT24 cell lines glioblastoma (GB) xenografts in a chicken chorioallantoic membrane (CAM) model. The study groups were: treated with 10 mM, 5 mM of NaDCA, and 5 mM, 2.5 mM of MgDCA, and controls. The U87 MG and PBT24 xenografts growth, frequency of tumor invasion into CAM, CAM thickening, and the number of blood vessels in CAM differed depending on the dichloroacetate salt treatment. NaDCA impact on U87 MG and PBT24 tumor on proliferating cell nunclear antigen (PCNA) and enhancer of zeste homolog 2 (EZH2) expression in the tumor was different, depending on the NaDCA dose. The 5 mM MgDCA impact was more potent and had similar effects on U87 MG and PBT24 tumors, and its impact was also reflected in changes in PCNA and EZH2 expression in tumor cells. The U87 MG and PBT24 tumor response variations to treatment with different NaDCA concentration on tumor growth or a contrast between NaDCA and MgDCA effectiveness may reflect some differences in U87 MG and PBT24 cell biology.
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http://dx.doi.org/10.1177/1559325821990166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923996PMC
February 2021

The physiology and genetics behind fruiting efficiency, a promising spike trait to improve wheat yield potential.

J Exp Bot 2021 Mar 3. Epub 2021 Mar 3.

Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires (CITNOBA, CONICET-UNNOBA-UNSADA). Monteagudo, Pergamino, Buenos Aires, Argentina.

The fruiting efficiency (FE, grains per g of spike dry weight at anthesis) was proposed as a promising spike trait to improve wheat yield potential, based on its functional relationship with grain number determination (the most important component associated with yield potential) and the evidence of trait variability in elite germplasm. During the last years, we have witnessed great advances in the understanding of the physiological and genetic bases of this trait. The present review summarises the recent heritability estimations and the genetic gains obtained when the fruiting efficiency was measured at maturity (FEm, grains per g of chaff) and used as selection criterion. In addition, by revising a detailed physiological approach based on the fertile floret efficiency (FFE, fertile florets per g of spike dry weight at anthesis) and grain set (grains per fertile floret), together with other spike fertility related traits, spike ideotypes for contrasting fruiting efficiencies are proposed. The novel genes and QTL available for using marker-assisted selection for fruiting efficiency and other spike fertility traits are also reviewed. The possible trade-off between FE and grain weight (GW) and the genes reported to alter this relation are revised. Finally, the benefits and future steps towards the use of fruiting efficiency as a selection criterion in breeding programs is discussed.
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http://dx.doi.org/10.1093/jxb/erab080DOI Listing
March 2021

Optimization and Validation of HS-GC/MS Method for the Controlled Release Study of Microencapsulated Specific Bioattractants for Target-Plaguicide Production.

Molecules 2021 Feb 13;26(4). Epub 2021 Feb 13.

Analytical Chemistry Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain.

Insect plagues are a problem often hard to solve due to the harmful effects caused by the pesticides used to combat them. Consequently, the pesticide market is increasingly trying to develop new technologies to prevent the unwanted effects that common plague treatments usually bring with them. In this work, four specific bioattractants of , extracted from fungi (β-ocimene, phenol, p-cresol, and indole) were microencapsulated with β-cyclodextrin in order to produce an economically and environmentally sustainable bait containing biocides in the near future. Cyclodextrins will retain these volatile compounds until their use by the consumer when the product comes into contact with water. Then, the bioattractants will be released in the medium in a controlled manner. An analytical methodology based on headspace extraction coupled to gas chromatography and mass spectrometry (HS-GC/MS) has been developed and validated following Environmental Protection Agency (EPA) and European Commission Directorate General for Health and Food Safety guidelines for the bioattractants controlled release study from the microencapsulated product. The analytical method has been shown to be accurate and precise and has the sensitivity required for controlled release studies of the four bioattractants analyzed. The release of the bioattractants from microencapsulated products achieved the "plateau" after 3 h in all cases.
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http://dx.doi.org/10.3390/molecules26040996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917701PMC
February 2021

Comment from the editor-in-chief about the Special Issue "A perspective of drug delivery and translational research in Europe".

Drug Deliv Transl Res 2021 Apr;11(2):341-342

CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela, Coruña, Spain.

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http://dx.doi.org/10.1007/s13346-021-00948-zDOI Listing
April 2021

Imaging of Endoplasmic Reticulum Ca in the Intact Pituitary Gland of Transgenic Mice Expressing a Low Affinity Ca Indicator.

Front Endocrinol (Lausanne) 2020 16;11:615777. Epub 2021 Feb 16.

Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.

The adenohypophysis contains five secretory cell types (somatotrophs, lactotrophs, thyrotrophs, corticotrophs, and gonadotrophs), each secreting a different hormone, and controlled by different hypothalamic releasing hormones (HRHs). Exocytic secretion is regulated by cytosolic Ca signals ([Ca]), which can be generated either by Ca entry through the plasma membrane and/or by Ca release from the endoplasmic reticulum (ER). In addition, Ca entry signals can eventually be amplified by ER release calcium-induced calcium release (CICR). We have investigated the contribution of ER Ca release to the action of physiological agonists in pituitary gland. Changes of [Ca] in the ER ([Ca]) were measured with the genetically encoded low-affinity Ca sensor GAP3 targeted to the ER. We used a transgenic mouse strain that expressed erGAP3 driven by a ubiquitous promoter. Virtually all the pituitary cells were positive for the sensor. In order to mimick the physiological environment, intact pituitary glands or acute slices from the transgenic mouse were used to image [Ca]. [Ca] was measured simultaneously with Rhod-2. Luteinizing hormone-releasing hormone (LHRH) or thyrotropin releasing hormone (TRH), two agonists known to elicit intracellular Ca mobilization, provoked robust decreases of [Ca] and concomitant rises of [Ca]. A smaller fraction of cells responded to thyrotropin releasing hormone (TRH). By contrast, depolarization with high K triggered a rise of [Ca] without a decrease of [Ca], indicating that the calcium-induced calcium-release (CICR) ryanodine receptor amplification mechanism is not present in these cells. Our results show the potential of transgenic ER Ca indicators as novel tools to explore intraorganellar Ca dynamics in pituitary gland .
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http://dx.doi.org/10.3389/fendo.2020.615777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921146PMC
February 2021

Recovery of Equine Oocytes in Ambulatory Practice and Potential Complications.

J Equine Vet Sci 2021 03 26;98:103324. Epub 2020 Nov 26.

InVitro Equinos/In Vitro Clonagem Animal SA, Campinas-Mogi Mirim, SP, Brazil. Electronic address:

Field collection of oocytes in mares using transvaginal follicular aspiration (TVA) for embryo production has the potential to revolutionate the equine industry. Protocols for TVA in specialized laboratory settings have been described in the scientific literature since the early 1980s. The objective of this study was to determine the success rate of TVA oocytes recovery under ambulatory conditions. A secondary goal of this study was to determine if TVA is associated with any health complications when performed by recently trained practitioners in the field. Follicles (n = 296) from 66 adult clinically healthy mares were aspirated over a period of 6 days. TVAs were performed by 22 veterinarians with 5-20 years of experience in equine and bovine reproductive medicine, but no previous experience in TVA. Oocytes (n = 145) were recovered. No short- or long-term systemic or local complications were observed following TVA in any of the mares used in this study. Fifty-six out of 66 mares became pregnant within 3 months following TVA. This study shows that with proper training, TVA can be successfully used to obtain equine oocytes with no health complications under field conditions in nonspecialized laboratory settings.
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http://dx.doi.org/10.1016/j.jevs.2020.103324DOI Listing
March 2021

Editorial note.

Drug Deliv Transl Res 2021 Apr;11(2):331-333

CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela, Spain.

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http://dx.doi.org/10.1007/s13346-021-00947-0DOI Listing
April 2021

Serum Levels of Clusterin, PKR, and RAGE Correlate with Amyloid Burden in Alzheimer's Disease.

J Alzheimers Dis 2021 ;80(3):1067-1077

Freshage Research Group, Department of Physiology, University of Valencia, CIBERFES-ISCIII, INCLIVA, Valencia, Spain.

Background: Alzheimer's disease (AD) is the most common form of dementia and biomarkers are essential to help in the diagnosis of this disease. Image techniques and cerebrospinal fluid (CSF) biomarkers are limited in their use because they are expensive or invasive. Thus, the search for blood-borne biomarkers is becoming central to the medical community.

Objective: The main objective of this study is the evaluation of three serum proteins as potential biomarkers in AD patients.

Methods: We recruited 27 healthy controls, 19 mild cognitive impairment patients, and 17 AD patients. Using the recent A/T/N classification we split our population into two groups (AD and control). We used ELISA kits to determine Aβ42, tau, and p-tau in CSF and clusterin, PKR, and RAGE in serum.

Results: The levels of serum clusterin, PKR, and RAGE were statistically different in the AD group compared to controls. These proteins showed a statistically significant correlation with CSF Aβ42. So, they were selected to generate an AD detection model showing an AUC-ROC of 0.971 (CI 95%, 0.931-0.998).

Conclusion: The developed model based on serum biomarkers and other co-variates could reflect the AD core pathology. So far, not one single blood-biomarker has been described, with effectiveness offering high sensitivity and specificity. We propose that the complexity of AD pathology could be reflected in a set of biomarkers also including clinical features of the patients.
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http://dx.doi.org/10.3233/JAD-201443DOI Listing
January 2021

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

Authors:
Jeroen R Huyghe Tabitha A Harrison Stephanie A Bien Heather Hampel Jane C Figueiredo Stephanie L Schmit David V Conti Sai Chen Conghui Qu Yi Lin Richard Barfield John A Baron Amanda J Cross Brenda Diergaarde David Duggan Sophia Harlid Liher Imaz Hyun Min Kang David M Levine Vittorio Perduca Aurora Perez-Cornago Lori C Sakoda Fredrick R Schumacher Martha L Slattery Amanda E Toland Fränzel J B van Duijnhoven Bethany Van Guelpen Antonio Agudo Demetrius Albanes M Henar Alonso Kristin Anderson Coral Arnau-Collell Volker Arndt Barbara L Banbury Michael C Bassik Sonja I Berndt Stéphane Bézieau D Timothy Bishop Juergen Boehm Heiner Boeing Marie-Christine Boutron-Ruault Hermann Brenner Stefanie Brezina Stephan Buch Daniel D Buchanan Andrea Burnett-Hartman Bette J Caan Peter T Campbell Prudence R Carr Antoni Castells Sergi Castellví-Bel Andrew T Chan Jenny Chang-Claude Stephen J Chanock Keith R Curtis Albert de la Chapelle Douglas F Easton Dallas R English Edith J M Feskens Manish Gala Steven J Gallinger W James Gauderman Graham G Giles Phyllis J Goodman William M Grady John S Grove Andrea Gsur Marc J Gunter Robert W Haile Jochen Hampe Michael Hoffmeister John L Hopper Wan-Ling Hsu Wen-Yi Huang Thomas J Hudson Mazda Jenab Mark A Jenkins Amit D Joshi Temitope O Keku Charles Kooperberg Tilman Kühn Sébastien Küry Loic Le Marchand Flavio Lejbkowicz Christopher I Li Li Li Wolfgang Lieb Annika Lindblom Noralane M Lindor Satu Männistö Sanford D Markowitz Roger L Milne Lorena Moreno Neil Murphy Rami Nassir Kenneth Offit Shuji Ogino Salvatore Panico Patrick S Parfrey Rachel Pearlman Paul D P Pharoah Amanda I Phipps Elizabeth A Platz John D Potter Ross L Prentice Lihong Qi Leon Raskin Gad Rennert Hedy S Rennert Elio Riboli Clemens Schafmayer Robert E Schoen Daniela Seminara Mingyang Song Yu-Ru Su Catherine M Tangen Stephen N Thibodeau Duncan C Thomas Antonia Trichopoulou Cornelia M Ulrich Kala Visvanathan Pavel Vodicka Ludmila Vodickova Veronika Vymetalkova Korbinian Weigl Stephanie J Weinstein Emily White Alicja Wolk Michael O Woods Anna H Wu Goncalo R Abecasis Deborah A Nickerson Peter C Scacheri Anshul Kundaje Graham Casey Stephen B Gruber Li Hsu Victor Moreno Richard B Hayes Polly A Newcomb Ulrike Peters

Gut 2021 Feb 25. Epub 2021 Feb 25.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.

Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.

Results: We identified 13 loci that reached genome-wide significance (p<5×10) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.

Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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http://dx.doi.org/10.1136/gutjnl-2020-321534DOI Listing
February 2021

A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes.

Front Cell Dev Biol 2020 7;8:622918. Epub 2021 Jan 7.

Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain.

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the "alternative" route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.
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http://dx.doi.org/10.3389/fcell.2020.622918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873843PMC
January 2021

A nanoemulsion/micelles mixed nanosystem for the oral administration of hydrophobically modified insulin.

Drug Deliv Transl Res 2021 Apr 11;11(2):524-545. Epub 2021 Feb 11.

Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, 15782, Santiago de Compostela, Spain.

The potential of nanoemulsions for the oral administration of peptides is still in its early stage. The aim of the present work was to rationally design, develop, and fully characterize a new nanoemulsion (NE) intended for the oral administration of hydrophobically modified insulin (HM-insulin). Specific components of the NE were selected based on their enhancing permeation properties as well as their ability to improve insulin association efficiency (Miglyol 812, sodium taurocholate), stability in the intestinal fluids, and mucodiffusion (PEGylated phospholipids and poloxamer 407). The results showed that the NE co-existed with a population of micelles, forming a mixed system that exhibited a 100% of HM-insulin association efficiency. The nanosystem showed good stability and miscibility in different bio-relevant media and displayed an acceptable mucodiffusive behavior in porcine mucus. In addition, it exhibited a high interaction with cell mono-cultures (Caco -2 and C2BBe1 human colon carcinoma Caco-2 clone cells) and co-cultures (C2BBe1 human colon carcinoma Caco-2 clone/HT29-MTX cells). The internalization in Caco-2 monolayers was also confirmed by confocal microscopy. Finally, the promising in vitro behavior of the nanosystem in terms of overcoming the biological barriers of the intestinal tract was translated into a moderate, although significant, hypoglycemic response (≈ 20-30%), following intestinal administration to both healthy and diabetic rat models. Overall, this information underlines the crucial steps to address when designing peptide-based nanoformulations to successfully overcome the intestinal barriers associated to the oral modality of administration.
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http://dx.doi.org/10.1007/s13346-021-00920-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987602PMC
April 2021

Local administration of IL-12 with an HC vector results in local and metastatic tumor control in pediatric osteosarcoma.

Mol Ther Oncolytics 2021 Mar 20;20:23-33. Epub 2020 Nov 20.

Health Research Institute of Navarra (IDISNA), 31008 Pamplona, Navarra, Spain.

Osteosarcoma is the most frequent and aggressive bone tumor in children and adolescents, with a long-term survival rate of 30%. Interleukin-12 (IL-12) is a potent cytokine that bridges innate and adaptive immunity, triggers antiangiogenic responses, and achieves potent antitumor effects. In this work, we evaluated the antisarcoma effect of a high-capacity adenoviral vector encoding mouse IL-12. This vector harbored a mifepristone-inducible system for controlled expression of IL-12 (High-Capacity adenoviral vector enconding the EF1α promoter [HCA-EFZP]-IL-12). We found that local administration of the vector resulted in a reduction in the tumor burden, extended overall survival, and tumor eradication. Moreover, long-term survivors exhibited immunological memory when rechallenged with the same tumor cells. Treatment with HCA-EFZP-IL-12 also resulted in a significant decrease in lung metastasis. Immunohistochemical analyses showed profound remodeling of the osteosarcoma microenvironment with decreases in angiogenesis and macrophage and myeloid cell numbers. In summary, our data underscore the potential therapeutic value of IL-12 in the context of a drug-inducible system that allows controlled expression of this cytokine, which can trigger a potent antitumor immune response in primary and metastatic pediatric osteosarcoma.
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http://dx.doi.org/10.1016/j.omto.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851487PMC
March 2021

Asymmetric flow field-flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers.

Drug Deliv Transl Res 2021 Apr 31;11(2):373-395. Epub 2021 Jan 31.

Center for Research in Molecular Medicine and Chronic Diseases, Singular Research Centers, 15782, Santiago de Compostela, Spain.

The importance of polymeric nanocarriers in the field of drug delivery is ever-increasing, and the accurate characterization of their properties is paramount to understand and predict their behavior. Asymmetric flow field-flow fractionation (AF4) is a fractionation technique that has gained considerable attention for its gentle separation conditions, broad working range, and versatility. AF4 can be hyphenated to a plurality of concentration and size detectors, thus permitting the analysis of the multifunctionality of nanomaterials. Despite this potential, the practical information that can be retrieved by AF4 and its possible applications are still rather unfamiliar to the pharmaceutical scientist. This review was conceived as a primer that clearly states the "do's and don'ts" about AF4 applied to the characterization of polymeric nanocarriers. Aside from size characterization, AF4 can be beneficial during formulation optimization, for drug loading and drug release determination and for the study of interactions among biomaterials. It will focus mainly on the advances made in the last 5 years, as well as indicating the problematics on the consensus, which have not been reached yet. Methodological recommendations for several case studies will be also included.
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http://dx.doi.org/10.1007/s13346-021-00918-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987708PMC
April 2021

The Challenges in the Follow-Up and Treatment of Brazilian Children with Hereditary Angioedema.

Int Arch Allergy Immunol 2021 Jan 28:1-7. Epub 2021 Jan 28.

Clinical Immunology, Faculdade de Medicina, Centro Universitario Saude ABC, Santo Andre, Brazil,

Introduction: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil.

Methods: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH.

Results: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients.

Conclusions: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.
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http://dx.doi.org/10.1159/000512944DOI Listing
January 2021