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Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy. ; This work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigacion Renal (REDINREN): RD16/0009, to M.R.-O., PI17/01495, DTS17/00203 and DTS19/00093 to J.E., PI16/02057, PI19/00815 to A.O.); Comunidad de Madrid ("NOVELREN" B2017/BMD-3751 to M.R.-O., B2017/BMD-3686 CIFRA2-CM to A.O.); the Jose Castillejo grant (CAS19/00133 to R.R.R.-D.); the "Juan de la Cierva Formacion" training program of the Ministerio de Economia, Industria y Competitividad (MINECO) supported the salary of S.R.-M. (FJCI-2016-29050); "Convocatoria Dinamizacion Europa Investigacion 2019" MINECO (EIN2019-103294 to M.R.-O. and S.R.-M.); Sociedad Espanola de Nefrologia (S.E.N. to M.R.-O.). Grants Fondecyt 1160465 to S.M. and PAI 82140017 to C.L. of Chile; ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O.; IMPROVE-PD project ("Identification and Management of Patients at Risk-Outcome and Vascular Events in Peritoneal Dialysis") funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 812699 to M.R.O.

Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, gamma delta T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications. ; This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 to M.R.-O.; PI17/01495, DTS17/00203, and DTS19/00093 to J.E.; PI16/02057 and PI19/00815 to A.O.; PI 15/00120 to R.S; PI18/0610 to J.M.V.; and Red de Investigacion Renal (REDINREN): RD16/0009 to M.R.-O., A.O., R.S., and J.M.V.); by Comunidad de Madrid ("NOVELREN" B2017/BMD-3751 to M.R.-O. and B2017/BMD-3686 CIFRA2-CM to A.O.); by the "Juan de la Cierva Formacion" training program of the Ministerio de Economia, Industria y Competitividad (MINECO) supporting the salary of S.R.-M. (FJCI-2016-29050); by "Convocatoria Dinamizacion Europa Investigacion 2019" MINECO (EIN2019-103294 to M.R.-O. and S.R.-M.); by Sociedad Espanola de Nefrologia (S.E.N. to M.R.-O.); by ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 toA.O; by IMPROVE-PD project ("Identification and Management of Patients at Risk-Outcome and Vascular Events in Peritoneal Dialysis") with funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 812699 to M.R.O., M.L.-C., and D.F.; and by the Spanish Ministry of Science and Innovation/Fondo Europeo de Desarrollo Regional (MICINN/FEDER) (PID2019-110132RB-I00) to M.L.-C.

[Background]: Intracerebral inoculation of extracts from post-mortem human Alzheimer's disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cytosolic protein aggregates, suggest that brain extracts contain key contributors that enhance the prion-like effect of amyloid-β. Nevertheless, these potential partners are still unknown due to the complexity of whole brain extracts. ; [Methods]: Herein, we established a method based on sequential detergent solubilization of post-mortem samples of human brains affected by Alzheimer's disease that strongly enrich amyloid-β aggregates by eliminating 92% of the remaining proteins. Internalization of Aβ1–42 from the enriched AD extracts was evaluated in vitro, and internalization of fluorescent-labeled AD extracts was also investigated in vivo. Furthermore, we carried out a molecular characterization of the Aβ-enriched fraction using label-free proteomics, studying the distribution of representative components in the amygdala and the olfactory cortex of additional human AD brain samples by immunohistochemistry. ; [Results]: Aβ1–42 from the enriched AD extracts are internalized into endothelial cells in vitro after 48 h. Furthermore, accumulation of fluorescent-labeled Aβ-enriched extracts into mouse microglia was observed in vivo after 4 months of intracerebral inoculation. Label-free proteomics (FDR < 0.01) characterization of the amyloid-β-enriched fraction from different post-mortem samples allowed for the identification of more than 130 proteins, several of which were significantly overrepresented (i.e., ANXA5 and HIST1H2BK; p < 0.05) and underrepresented (i.e., COL6A or FN1; p < 0.05) in the samples with Alzheimer's disease. We were also able to identify proteins exclusively observed in Alzheimer's disease (i.e., RNF213) or only detected in samples not affected by the disease (i.e., CNTN1) after the enrichment process. Immunohistochemistry against these proteins in additional tissues revealed their particular distribution in the amygdala and the olfactory cortex in relation to the amyloid-β plaque. ; [Conclusions]: Identification and characterization of the unique features of these extracts, in terms of amyloid-β enrichment, identification of the components, in vitro and in vivo cell internalization, and tissue distribution, constitute the best initial tool to further investigate the seeding and transmissibility proposed in the prion-like hypothesis of Alzheimer's disease. ; Sponsored by the Spanish Ministry of Economy and Competitiveness-FEDER (grant # SAF2016-75768-R) to AMM, MINECO-RETOS (AEI-FEDER) to MDP, and the Autonomous Government of Castilla-La Mancha/FEDER (grant no. SBPLY/ 17/180501/000430) to AMM and DSS. ; Peer reviewed

This position document has been developed by the Dysphagia Working Group, a committee of members from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society, and invited experts. It consists of 12 sections that cover all aspects of clinical management of oropharyngeal dysphagia (OD) related to geriatric medicine and discusses prevalence, quality of life, and legal and ethical issues, as well as health economics and social burden. OD constitutes impaired or uncomfortable transit of food or liquids from the oral cavity to the esophagus, and it is included in the World Health Organization's classification of diseases. It can cause severe complications such as malnutrition, dehydration, respiratory infections, aspiration pneumonia, and increased readmissions, institutionalization, and morbimortality. OD is a prevalent and serious problem among all phenotypes of older patients as oropharyngeal swallow response is impaired in older people and can cause aspiration. Despite its prevalence and severity, OD is still underdiagnosed and untreated in many medical centers. There are several validated clinical and instrumental methods (videofluoroscopy and fiberoptic endoscopic evaluation of swallowing) to diagnose OD, and treatment is mainly based on compensatory measures, although new treatments to stimulate the oropharyngeal swallow response are under research. OD matches the definition of a geriatric syndrome as it is highly prevalent among older people, is caused by multiple factors, is associated with several comorbidities and poor prognosis, and needs a multidimensional approach to be treated. OD should be given more importance and attention and thus be included in all standard screening protocols, treated, and regularly monitored to prevent its main complications. More research is needed to develop and standardize new treatments and management protocols for older patients with OD, which is a challenging mission for our societies.

Open Science calls for transparent science and involvement of various stakeholders. Here are examples of and advice for meaningful stakeholder engagement. ; Ana Lúcia Mena was funded by the Portuguese Foundation for Science and Technology—FCT. The Soy-in-1000-gardens project and the Liver project were funded within the Grand Challenges Program of VIB. This VIB Program received support from the Flemish Government under the Management Agreement 2017–2021 (VR 2016 2312 Doc.1521/4). Inês Pinheiro funded by ANR LabEx DEEP (11-LBX-0044, ANR-10-IDEX-0001-02) and by Institut Curie. We acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya. We acknowledge funding from European Commission (EC): 741527

The lack of tools for the precise manipulation of the tick microbiome is currently a major limitation to achieve mechanistic insights into the tick microbiome. Anti-tick microbiota vaccines targeting keystone bacteria of the tick microbiota alter tick feeding, but their impact on the taxonomic and functional profiles of the tick microbiome has not been tested. In this study, we immunized a vertebrate host model (Mus musculus) with live bacteria vaccines targeting keystone (i.e., Escherichia-Shigella) or non-keystone (i.e., Leuconostoc) taxa of tick microbiota and tested the impact of bacterial-specific antibodies (Abs) on the structure and function of tick microbiota. We also investigated the effect of these anti-microbiota vaccines on mice gut microbiota composition. Our results showed that the tick microbiota of ticks fed on Escherichia coli-immunized mice had reduced Escherichia-Shigella abundance and lower species diversity compared to ticks fed on control mice immunized with a mock vaccine. Immunization against keystone bacteria restructured the hierarchy of nodes in co-occurrence networks and reduced the resistance of the bacterial network to taxa removal. High levels of E. coli-specific IgM and IgG were negatively correlated with the abundance of Escherichia-Shigella in tick microbiota. These effects were not observed when Leuconostoc was targeted with vaccination against Leuconostoc mesenteroides. Prediction of functional pathways in the tick microbiome using PICRUSt2 revealed that E. coli vaccination reduced the abundance of lysine degradation pathway in tick microbiome, a result validated by qPCR. In contrast, the gut microbiome of immunized mice showed no significant alterations in the diversity, composition and abundance of bacterial taxa. Our results demonstrated that anti-tick microbiota vaccines are a safe, specific and an easy-to-use tool for manipulation of vector microbiome. These results guide interventions for the control of tick infestations and pathogen infection/transmission. ; UMR BIPAR is supported by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases" (grant no. ANR-10-LABX-62-IBEID). Alejandra Wu-Chuang is supported by Programa Nacional de Becas de Postgrado en el Exterior "Don Carlos Antonio López" (grant no. 205/2018). ; Peer reviewed

Current antiretroviral treatment (ART) may control HIV-1 replication but it cannot cure the infection due to the formation of a reservoir of latently infected cells. CD4+ T cell activation during HIV-1 infection eliminates the antiviral function of the restriction factor SAMHD1, allowing proviral integration and the reservoir establishment. The role of tyrosine kinases during T-cell activation is essential for these processes. Therefore, the inhibition of tyrosine kinases could control HIV-1 infection and restrict the formation of the reservoir. A family of tyrosine kinase inhibitors (TKIs) is successfully used in clinic for treating chronic myeloid leukemia (CML). The safety and efficacy against HIV-1 infection of five TKIs was assayed in PBMCs isolated from CML patients on prolonged treatment with these drugs that were infected ex vivo with HIV-1. We determined that the most potent and safe TKI against HIV-1 infection was dasatinib, which preserved SAMHD1 antiviral function and avoid T-cell activation through TCR engagement and homeostatic cytokines. Imatinib and nilotinib showed lower potency and bosutinib was quite toxic in vitro. Ponatinib presented similar profile to dasatinib but as it has been associated with higher incidence of arterial ischemic events, dasatinib would be the better choice of TKI to be used as adjuvant of ART in order to avoid the establishment and replenishment of HIV-1 reservoir and move forward towards an HIV cure. ; This work was supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-44677-R, SAF2016-78480-R, FIS PI12/00506, and FIS PI12/00969); the Spanish AIDS Research Network RD16CIII/0002/0001 that is included in Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2016-2020, Instituto de Salud Carlos III, European Region Development Fund (ERDF); Bristol-Myers Squibb [BMS AI471-041]. The work of Elena Mateos is supported by the Spanish Ministry of Economy and Competitiveness SAF2016-78480-R. The work of María Rosa López-Huertas is financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) and by Spanish Ministry of Economy and Competitiveness (PIE 13/00040). Dr. Montserrat Plana is a researcher at the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and is supported by the Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya, Spain). Dr. Juan Ambrosioni developed this work in the framework of a 'Juan de la Cierva 2012' post-doctoral program, Ministerio de Competitividad. Dr. Jose M. Miró received a personal 80:20 research grant from IDIBAPS (Barcelona, Spain), 2017-2019. ; Sí

The premise of this book is, simply, that politicians matter—that an understanding of the role played by politicians in the way that politics is carried out in their countries is, far from constituting a resurrection of outdated elitist theories, of vital importance in present-day Latin America. The authors consider politicians as both cause and effect. Drawing on pioneering field research on the opinions of Latin American legislators in 17 countries, they focus on two broad topics: political systems, as reflected in politicians' perspectives on the democracies and party organizations of which they are a part; and the role played by ideology, not only in shaping positions on issues, but also as a factor that gives coherence to parties. Their seminal work is central to the current political dynamics in the region, as well as to broader debates in political science

Chronic kidney disease (CKD) is one of the fastest-growing causes of death and is predicted to become by 2040 the fifth global cause of death. CKD is characterized by increased oxidative stress and chronic inflammation. However, therapies to slow or prevent CKD progression remain an unmet need. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in protection against oxidative stress and regulation of the inflammatory response. Consequently, the use of compounds targeting Nrf2 has generated growing interest for nephrologists. Pre-clinical and clinical studies have demonstrated that Nrf2-inducing strategies prevent CKD progression and protect from acute kidney injury (AKI). In this article, we review current knowledge on the protective mechanisms mediated by Nrf2 against kidney injury, novel therapeutic strategies to induce Nrf2 activation, and the status of ongoing clinical trials targeting Nrf2 in renal diseases ; The authors'work has been supported by grants FIS/Fondos FEDER (PI17/00130, PI17/00257, PI17/01495, PI18/01386, PI19/00815, PI20/00375, PI20/00487 ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369, FJC2019-042028), The "PFIS" and "Sara Borrell" training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M (CD19/00021), and CH-B (CP16/00017). Spanish Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba (to J.M.V.)

Ecological restoration is key to counteracting anthropogenic degradation of biodiversity and to reducing disaster risk. However, there is limited knowledge of barriers hindering the wider implementation of restoration practices, despite high level political priority to halt the loss of biodiversity. In Europe, progress on ecological restoration has been slow and insufficient to meet international agreements and comply with European Union Nature Directives. We assessed European restoration experts' perceptions on barriers to restoration in Europe, and their relative importance, through a multiple expert consultation using a Delphi process. We found that experts share a common multi‐dimensional concept of ecological restoration. Experts identified a large number of barriers (33) to the advancement of ecological restoration in Europe. Major barriers pertained to the socio‐economic, not the environmental, domain. The three most important being insufficient funding, conflicting interests among different stakeholders and low political priority given to restoration. Our results emphasize the need to increase political commitment at all levels, comply with existing nature laws, and optimize the use of financial resources by increasing funds for ecological restoration and eradicate environmentally harmful subsidies. The experts also call for the integration of ecological restoration into land‐use planning and facilitating stakeholders' collaboration. Our study identifies key barriers, discusses ways to overcome the main barriers to ER in Europe, and contributes knowledge to support the implementation of the European Biodiversity Strategy for 2030, and the EU 2030 Restoration Plan in particular. ; We appreciate the support given by BiodivERsA (project funded under the EU Horizon 2020 ERA-NET COFUND scheme), and the EKLIPSE project (European Union Horizon 2020 grant agreement 690474), and particularly by Juliette C. Young. JCS research is financially supported by the Spanish Ministry of Science, Education and Universities and European Regional Development Funds (FEDER; project COSTERA, RTI2018-095954-B-I00). PMRG research is funded by the Portuguese Foundation for Science and Technology (FCT) through FCT Investigator Program grant number IF/00059/2015, and Centro de Estudos Florestais is supported by FCT grants UID/AGR/00239/2019 and UIDB/00239/2020.

Tick-borne infectious diseases and allergies are a growing problem worldwide. Tick bite allergy has been associated with the direct effect of immunoglobulin E (IgE) response to tick salivary antigens, or secondary to the induction of allergy to red meat consumption through IgE antibodies against the carbohydrate α-Gal (Gal α 1-3Gal β 1-(3)4GlcNAc-R). However, despite the growing burden of this pathology, the proteins associated with anaphylaxis to tick bite have not been characterized. To address this question, a comparative proteomics approach was used to characterize tick proteins producing an IgE antibody response in a healthy individual with record of tick bites, which had not resulted in any allergic reactions, and two patients with anaphylactic reactions to Rhipicephalus bursa or Hyalomma marginatum tick bites. Both patients and the healthy individual were red meat tolerant. The results supported a patientspecific IgE antibody response to tick species responsible for the anaphylaxis to tick bite. Both patients and the healthy individual serologically recognized tick proteins with and without a-Gal modifications, with proteins differentially recognized by patients but not control sera. These proteins could be used as potential antigens for diagnostics, treatment and prevention of tick bite-induced allergies. ; Part of this research was supported by the European Union FP7 ANTIGONE project number 278976. L.M-H was supported by the University of Castilla La Mancha (UCLM, Spain) fellowship. M.V and I.G.FM were supported by the Research Plan of UCLM. F.R-F was supported by the 'Ramón y Cajal' program of the Spanish Ministry of Economy and Competitiveness. ; Peer Reviewed

The neuronal long isoform of Fas Apoptotic Inhibitory Molecule (FAIM-L) protects from death receptor (DR)-induced apoptosis, yet its mechanism of protection remains unknown. Here, we show that FAIM-L protects rat neuronal Type II cells from Fas-induced apoptosis. XIAP has previously emerged as a molecular discriminator that is upregulated in Type II and downregulated in Type I apoptotic signaling. We demonstrate that FAIM-L requires sustained endogenous levels of XIAP to protect Type II cells as well as murine cortical neurons from Fas-induced apoptosis. FAIM-L interacts with the BIR2 domain of XIAP through an IAP-binding motif, the mutation of which impairs the antiapoptotic function of FAIM-L. Finally, we report that FAIM-L inhibits XIAP auto-ubiquitinylation and maintains its stability, thus conferring protection from apoptosis. Our results bring new understanding of the regulation of endogenous XIAP by a DR antagonist, pointing out at FAIM-L as a promising therapeutic tool for protection from apoptosis in pathological situations where XIAP levels are decreased. ; This work was funded by the Spanish Government Ministerio de Sanidad y Consumo (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, CB06/05/1104 to J.X.C.), Ministerio de Economía y Competitividad (SAF2010–19953 to J.X.C.; SAF2012–31485 to V.J.Y.), Instituto de Salud Carlos III (CP11/00052 to M.F.S.), and the Generalitat de Catalunya (Suport als Grups de Recerca Consolidats 2009SGR346). F.M.-F. and L.P.-F. are supported by postgraduate fellowships from the Spanish Government Ministerio de Educación y Ciencia. J.U. is supported by a postgraduate fellowship from the Generalitat de Catalunya. R.S.M. and V.J.Y. were under the Juan de la Cierva and the Ramon y Cajal programs, respectively, from the Ministerio de Educación y Ciencia (Spain), cofinanced by the European Social Fund. M.F.S. is under the Miguel Servet program from the Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund.