Beneficial effects of melatonin on liver fibrosis: A systematic review of current biological evidence

[EN] Hepatic fibrosis is a reversible response to either acute or chronic cellular injury froma wide variety of etiologies, characterized by excessive deposition of extracellularmatrix resulting in liver dysfunction and cirrhosis. Melatonin (N‐acetyl‐5‐methoxytryptamine), the main product secreted by the pineal gland, is a multitaskingindolamine with important physiological functions such as anti‐inflammatory andantioxidant actions, modulation of circadian rhythms, and immune system enhance-ment. Among the numerous biological activities of melatonin, its antifibrotic effectshave received increasingly more attention. In this study, we performed a systematicreview of publications of the last 10 years evaluating the mechanisms of action ofmelatonin against liver fibrosis. The study protocol was registered at PROSPERO(CRD42022304744). Literature research was performed employing PubMed,Scopus, and Web of Science (WOS) databases, and after screening, 29 articleswere included. Results from the selected studies provided denoted the usefulactions of melatonin on the development, progression, and evolution of liver fibrosis.Melatonin antifibrotic effects in the liver involved the reduction of profibrogenicmarkers and modulation of several cellular processes and molecular pathways,mainly acting as an antioxidant and anti‐inflammatory agent. In addition, theindolamine influenced different molecular processes, such as hepatocyte apoptosis,modulation of autophagy and mitophagy, restoration of circadian rhythms, andmodulation of microRNAs, among others. Although some limitations have beenfound regarding variability in the study design, the findings here summarized displaythe potential role of melatonin in ameliorating the development of liver fibrosis andits possible progression to liver cirrhosis and hepatocarcinomaS

Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; P 85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Characterization of the platelet phenotype caused by a germline RUNX1 Variant in a CRISPR/Cas9-generated murine model

RUNX1-related disorder (RUNX1-RD) is caused by germline variants affecting the RUNX1 gene. This rare, heterogeneous disorder has no specific clinical or laboratory phenotype, making genetic diagnosis necessary. Although international recommendations have been established to classify the pathogenicity of variants, identifying the causative alteration remains a challenge in RUNX1-RD. Murine models may be useful not only for definitively settling the controversy about the pathogenicity of certain RUNX1 variants, but also for elucidating the mechanisms of molecular pathogenesis. Therefore, we developed a knock-in murine model, using the CRISPR/Cas9 system, carrying the RUNX1 p.Leu43Ser variant (mimicking human p.Leu56Ser) to study its pathogenic potential and mechanisms of platelet dysfunction. A total number of 75 mice were generated; 25 per genotype (RUNX1WT/WT, RUNX1WT/L43S, and RUNX1L43S/L43S). Platelet phenotype was assessed by flow cytometry and confocal microscopy. On average, RUNX1L43S/L43S and RUNX1WT/L43S mice had a significantly longer tail-bleeding time than RUNX1WT/WT mice, indicating the variant's involvement in hemostasis. However, only homozygous mice displayed mild thrombocytopenia. RUNX1L43S/L43S and RUNX1WT/L43S displayed impaired agonist-induced spreading and α-granule release, with no differences in δ-granule secretion. Levels of integrin αIIbβ3 activation, fibrinogen binding, and aggregation were significantly lower in platelets from RUNX1L43S/L43S and RUNX1WT/L43S using phorbol 12-myristate 13-acetate (PMA), adenosine diphosphate (ADP), and high thrombin doses. Lower levels of PKC phosphorylation in RUNX1L43S/L43S and RUNX1WT/L43S suggested that the PKC-signaling pathway was impaired. Overall, we demonstrated the deleterious effect of the RUNX1 p.Leu56Ser variant in mice via the impairment of integrin αIIbβ3 activation, aggregation, α-granule secretion, and platelet spreading, mimicking the phenotype associated with RUNX1 variants in the clinical setting.This work was partially supported by grants from Instituto de Salud Carlos III (ISCIII) and Feder (PI17/01311, PI17/01966, and CB15/00055), Fundación Séneca (19873/GERM/15), Gerencia Regional de Salud (GRS 2061A/19 and 1647/A/17), Fundación Mutua Madrileña (FMM, AP172142019), and Sociedad Española de Trombosis y Hemostasia (SETH-FETH; Premio López Borrasca 2019 and Ayuda a Grupos de Trabajo en Patología Hemorrágica 2019). The authors' research on IPDs is conducted in accordance with the aims of the Functional and Molecular Characterization of Patients with Inherited Platelet Disorders Project, which is supported by the Hemorrhagic Diathesis Working Group of the Spanish Society of Thrombosis and Haemostasis. A.M.-Q., C.F.-I., and L.H.-C. were supported by predoctoral grants from the Junta de Castilla y León, Spain. E.V. was supported by the predoctoral grant from the University of Salamanca, Spain. IG-T and RB were supported by "Contratos postdoctorales Programa II) from the University of Salamanca, Spain

Differential profile in inflammatory and mineral metabolism biomarkers in patients with ischemic heart disease without classical coronary risk factors

AbstractBackgroundPatients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRFs) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF.MethodsWe studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), galectin-3, N-terminal fragment of brain natriuretic peptide (NT-pro-BNP), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate.ResultsTwenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients.No-CRF patients showed lower hs-CRP (2.574±3.120 vs. 4.554±9.786mg/L; p=0.018), MCP-1 (114.75±36.29 vs. 143.56±65.37pg/ml; p=0.003), and FGF-23 (79.28±40.22 vs. 105.17±156.61RU/ml; p=0.024), and higher calcidiol (23.66±9.12 vs. 19.49±8.18ng/ml; p=0.025) levels. At follow-up, 10.0% vs. 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (p=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated with a better prognosis.ConclusionsCHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID

Background: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. Methods: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Results: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). Conclusion: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful

Electrostatic charge dependence on surface hydroxylation for different Al 2O 3 powders

The effect of surface chemistry on the electrostatic charge in α-Al 2O 3 powders was studied. Net charge and tribo-charge of dry powders were measured by the Faraday double cup procedure. High electrostatic charge values were observed in powders with high surface hydroxylation by IR spectroscopy. The nature of hydroxyl groups at the surface determines the polarity of the electrostatic charge. Mixture of particles having intrinsic electrostatic positive and negative charges follows the lever rule. Dry mixtures of differently charged particles favour the dispersion of smaller particles on the surface of the largest ones. An effective random dispersion was achieved by a low-energy process that allowed preserving the morphology of the supporting and supported particles. © 2011 Elsevier Ltd and Techna Group S.r.l. All rights reserved.This work was supported by the CSIC project PIF MAGIN and by CICYT projects MAT2007-66845-C02-01 and MAT2010-21088-C03-01.Peer Reviewe

Some clues about the interphase reaction between ZnO and MnO2 oxides

6 páginas, 8 figuras, 1 tabla.Raman spectroscopy is used to evidence both the nature of the interphase reaction between ZnO and MnO2 particles and its kinetic evolution. Zn cations migrate from the ZnO grains during oxygen vacancies formation process and diffuse into the MnO2 particles leading to an interphase region with an intermediate valence Mn+3–O–Mn+4. Large amounts of desorbed Zn cations promote the formation of ZnMn2O4 structure, in addition to the intermediate valence state. The system evolves towards complete formation of the spinel phase at higher thermal treatment times. The reactivity of the ZnO plays an important role in the formation of this interphase. Low-reactivity ZnO powder, in which the oxygen vacancies are previously produced, shows a stabilization of the intermediate valence state with very limited formation of the spinel phase. A clear correlation between the amount of the intermediate state interphase and the magnetic properties has been established.The authorsexpresstheirthankstotheCICYTProjects MAT2007-66845-C02-01andFIS2008-06249andtotheMAGIN ProjectPIF2006-60f0121fortheirfinancialsupport.F.Rubio- Marcos thankstheFPI-CAM-FSEprogramfortheresearchgrant.Peer reviewe

Some clues about the interphase reaction between ZnO and MnO2 oxides

6 páginas, 8 figuras, 1 tabla.Raman spectroscopy is used to evidence both the nature of the interphase reaction between ZnO and MnO2 particles and its kinetic evolution. Zn cations migrate from the ZnO grains during oxygen vacancies formation process and diffuse into the MnO2 particles leading to an interphase region with an intermediate valence Mn+3–O–Mn+4. Large amounts of desorbed Zn cations promote the formation of ZnMn2O4 structure, in addition to the intermediate valence state. The system evolves towards complete formation of the spinel phase at higher thermal treatment times. The reactivity of the ZnO plays an important role in the formation of this interphase. Low-reactivity ZnO powder, in which the oxygen vacancies are previously produced, shows a stabilization of the intermediate valence state with very limited formation of the spinel phase. A clear correlation between the amount of the intermediate state interphase and the magnetic properties has been established.The authorsexpresstheirthankstotheCICYTProjects MAT2007-66845-C02-01andFIS2008-06249andtotheMAGIN ProjectPIF2006-60f0121fortheirfinancialsupport.F.Rubio- Marcos thankstheFPI-CAM-FSEprogramfortheresearchgrant.Peer reviewe

Procedimiento para la dispersión de nanopartículas en seco y la obtención de estructuras jerárquicas y recubrimientos

[EN] The invention relates to a method for the dispersion of synthetic or natural nanoparticles and nanocomposite materials and to the use thereof in different sectors including those of ceramics, coatings, polymers, construction, paints, catalysis, pharmaceuticals and powdered materials in general.[ES] La presente invención se refiere a un procedimiento para la dispersión de nanopartículas sintéticas o naturales y de materiales nanocompuestos, y sus aplicaciones en diferentes sectores, entre los que destacan los sectores de cerámica, de recubrimientos, de polímeros, de la construcción, de pinturas, de catálisis, farmacéutico o de materiales pulvenilentos en general.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A1 Solicitud de patentes con informe sobre el estado de la técnic

Glazed ceramic piece

[ES] Una pieza cerámica esmaltada que comprende: a) un soporte cerámico. b) una capa final de esmalte cerámico, c) una composición luminiscente integrada en una zona, o varias zonas, discretas de la capa final de esmalte, tal que dicha composición luminiscente comprende: - cristalizaciones con estructura de feldespato; - una fase vítrea; y - partículas cristalinas que comprenden uno o más óxidos de lantánido.[EN] A glazed ceramic piece comprising: a) a ceramic support. b) a final layer of ceramic glaze, c) a luminescent composition integrated into a discrete zone, or zones, of the final layer of glaze, such that said luminescent composition comprises: - crystallizations with a feldspar structure; - a glassy phase; and - crystalline particles comprising one or more lanthanide oxides.NoConsejo Superior de Investigaciones Científicas (CSIC), Keraben Grupo SauA1 Solicitud de patente con informe sobre el estado de la técnic