Cord blood cardiovascular biomarkers in left-sided congenital heart disease.

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013-2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4-3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8-21.4) vs. favorable outcome 51.7 ng/mL (13.8-73.9) vs. poor outcome 25.1 ng/mL (6.9-39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8-23.9) vs. favorable outcome 12.8 pg/mL (11.7-13.6) vs. poor outcome 11.0 pg/mL (8.8-15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5-776.3) vs. favorable outcome 617.0 pg/mL (389.8-1087.8) vs. poor outcome 1450.0 pg/mL (919.0-1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3-2715.8) vs. favorable outcome (1848.3 pg/mL (646.9-2313.6) vs. poor outcome 259.0 pg/mL (182.0-606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Understanding How Microplastics Affect Marine Biota on the Cellular Level Is Important for Assessing Ecosystem Function: A Review

Plastic has become indispensable for human life. When plastic debris is discarded into waterways, these items can interact with organisms. Of particular concern are microscopic plastic particles (microplastics) which are subject to ingestion by several taxa. This review summarizes the results of cutting-edge research about the interactions between a range of aquatic species and microplastics, including effects on biota physiology and secondary ingestion. Uptake pathways via digestive or ventilatory systems are discussed, including (1) the physical penetration of microplastic particles into cellular structures, (2) leaching of chemical additives or adsorbed persistent organic pollutants (POPs), and (3) consequences of bacterial or viral microbiota contamination associated with microplastic ingestion. Following uptake, a number of individual-level effects have been observed, including reduction of feeding activities, reduced growth and reproduction through cellular modifications, and oxidative stress. Microplastic-associated effects on marine biota have become increasingly investigated with growing concerns regarding human health through trophic transfer. We argue that research on the cellular interactions with microplastics provide an understanding of their impact to the organisms’ fitness and, therefore, its ability to sustain their functional role in the ecosystem. The review summarizes information from 236 scientific publications. Of those, only 4.6% extrapolate their research of microplastic intake on individual species to the impact on ecosystem functioning. We emphasize the need for risk evaluation from organismal effects to an ecosystem level to effectively evaluate the effect of microplastic pollution on marine environments. Further studies are encouraged to investigate sublethal effects in the context of environmentally relevant microplastic pollution conditions

Behavioral and Cognitive Improvement Induced by Novel Imidazoline I2 Receptor Ligands in Female SAMP8 Mice

As populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer's disease have become more common. I2-Imidazoline receptors (I2-IR) are widely distributed in the central nervous system, and dysregulation of I2-IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I2-IR ligands potentially contribute to the delay of neurodegeneration. In vivo studies in the female senescence accelerated mouse-prone 8 mice have shown that treatment with I2-IR ligands, MCR5 and MCR9, produce beneficial effects in behavior and cognition. Changes in molecular pathways implicated in oxidative stress, inflammation, synaptic plasticity, and apoptotic cell death were also studied. Furthermore, treatments with these I2-IR ligands diminished the amyloid precursor protein processing pathway and increased Aβ degrading enzymes in the hippocampus of SAMP8 mice. These results collectively demonstrate the neuroprotective role of these new I2-IR ligands in a mouse model of brain aging through specific pathways and suggest their potential as therapeutic agents in brain disorders and age-related neurodegenerative diseases. Keywords Imidazoline I2 receptors (2-imidazolin-4-yl)phosphonates Behavior Cognition Neurodegeneration Neuroprotection Agin

Posterior Wnts have distinct roles in specification and patterning of the planarian posterior region

The wnt signaling pathway is an intercellular communication mechanism essential in cell-fate specification, tissue patterning and regional-identity specification. A βcatenin-dependent signal specifies the AP (Anteroposterior) axis of planarians, both during regeneration of new tissues and during normal homeostasis. Accordingly, four wnts (posterior wnts) are expressed in a nested manner in central and posterior regions of planarians. We have analyzed the specific role of each posterior wnt and the possible cooperation between them in specifying and patterning planarian central and posterior regions. We show that each posterior wnt exerts a distinct role during re-specification and maintenance of the central and posterior planarian regions, and that the integration of the different wnt signals (βcatenin dependent and independent) underlies the patterning of the AP axis from the central region to the tip of the tail. Based on these findings and data from the literature, we propose a model for patterning the planarian AP axis

Albuminuria Is Associated with Hepatic Iron Load in Patients with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome

Background: Increased albuminuria is associated with increased serum ferritin, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Liver iron accumulation is also related to hyperferritinemia, insulin resistance, and NAFLD; however, there is no evidence on its relationship with albuminuria. Aims: To assess the relationship between hepatic iron load and urine albumin-to-creatinine ratio (UACR) in patients with metabolic syndrome (MetS) and NAFLD. Methods: In total, 75 MetS and NAFLD patients (aged 40–60 years, BMI 27–40 kg/m2) were selected from a cohort according to available data on hepatic iron load (HepFe) by magnetic resonance imaging (MRI). Subjects underwent anthropometric measurements, biochemistry testing, and liver MRI. Increased albuminuria was defined by UACR. Results: UACR correlated with NAFLD, HepFe, triglycerides, serum ferritin, fasting insulin, insulin resistance (calculated using the homeostatic model assessment for insulin resistance—HOMA-IR- formula), and platelets (p &lt; 0.05). Multiple regression analysis adjusted for gender, age, eGFR, HbA1c, T2DM, and stages of NAFLD, found that HepFe (p = 0.02), serum ferritin (p = 0.04), fasting insulin (p = 0.049), and platelets (p = 0.009) were associated with UACR (R2 = 0.370; p = 0.007). UACR, liver fat accumulation, serum ferritin, and HOMA-IR increased across stages of HepFe (p &lt; 0.05). Patients with severe NAFLD presented higher HepFe, fasting insulin, HOMA-IR, and systolic blood pressure as compared to patients in NAFLD stage 1 (p &lt; 0.05). Conclusion: Hepatic iron load, serum ferritin, fasting insulin, and platelets were independently associated with albuminuria. In the context of MetS, increased stages of NAFLD presented higher levels of HepFe. Higher levels of HepFe were accompanied by increased serum ferritin, insulin resistance, and UACR. The association between iron accumulation, MetS, and NAFLD may represent a risk factor for the development of increased albuminuria