Fate and effects of uncoated ZnO nanoparticles on nine crops exposed in two agricultural soils, a calcareous and an acidic soil.

The nanotechnology has a wide range of applications including those that deliberately release nanoparticles (NPs) into the environment. The use of nanoformulations containing agrochemicals to soils provides an efficient way to apply pesticides and fertilizers in a controlled mode. The zinc oxide nanoparticles (ZnO NPs) are of particular interest due to their increasing incorporation into agricultural products

Toxicity of ZnO nanoparticles, ZnO bulk and ZnCl2 on earthworms in a spiked natural soil and toxicological effects of leachates on aquatic organisms

The present study assessed the uptake and toxicity of ZnO nanoparticles (NPs), ZnO bulk, and ZnCl2 salt in earthworms in spiked agricultural soils. In addition, the toxicity of aqueous extracts to Daphnia magna and Chlorella vulgaris was analyzed to determine the risk of these soils to the aquatic compartment. We then investigated the distribution of Zn in soil fractions to interpret the nature of toxicity. Neither mortality nor differences in earthworm body weight were observed compared with the control. The most sensitive end point was reproduction. ZnCl2 was notably toxic in eliminating the production of cocoons. The effects induced by ZnO-NPs and bulk ZnO on fecundity were similar and lower than those of the salt. In contrast to ZnO bulk, ZnO-NPs adversely affected fertility. The internal concentrations of Zn in earthworms in the NP group were greater than those in the salt and bulk groups, although bioconcentration factors were consistently <1. No relationship was found between toxicity and internal Zn amounts in earthworms. The results from the sequential extraction of soil showed that ZnCl2 displayed the highest availability compared with both ZnO. Zn distribution was consistent with the greatest toxicity showed by the salt but not with Zn body concentrations. The soil extracts from both ZnO-NPs and bulk ZnO did not show effects on aquatic organisms (Daphnia and algae) after short-term exposure. However, ZnCl2 extracts (total and 0.45-μm filtered) were toxic to Daphnia

Soil pH effects on the Toxicity of zinc oxide nanoparticles to soil bacterial communities.

The environmental levels of ZnO nanoparticles (nZnO) are increasing continually given the widespread and expanding applications of this material. Soil pH appears to be one of the key factors affecting the behavior and toxicity of metal nanoparticles in soi

Influence of soil pH in the effects of ZnONPs on the antioxidant activities and Zn uptake in three plant species (T aestivum, R. sativus and Z. mays)

In recent years, the study of phytotoxicity of NPs has made rapid progress, but important issues remain to be solved, among them, the role of soil and the importance of the physicochemical soil characteristics for their toxicity and accumulation potential

Insights into the Pharmacokinetics and In Vitro Cell-Based Studies of the Imidazoline I2 Receptor Ligand B06

Abstract: The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I2 receptors (I2‐IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I2‐IR by developing structurally new molecules, in particular, a family of bicyclic α‐iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age‐related cognitive decline and the other for Alzheimer's disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME‐Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de‐risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson's disease (PD). B06 rescued the human dopaminergic cell line SH‐SY5Y from death after treatment with 6‐hydroxydopamine (6‐OHDA) and showed a crucial anti‐inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I2‐IR as a fresh approach for the therapy of ND

Feasibility of Double-Blind Clinical Trials with Oral Diacetylmorphine: A Randomized Controlled Phase II Study in an Inpatient Setting

The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians' ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments

Effect of a dietary intervention based on the mediterranean diet on the quality of life of patients recovered from depression: analysis of the PREDIDEP randomized trial

Introduction: There is substantial evidence supporting that improving diet quality leads to improved healthrelated quality of life (HRQoL). Our major aim was to assess the effectiveness of a Mediterranean diet–based nutritional intervention to improve HRQoL in the context of a secondary prevention trial of depression. Secondarily to assess its effectiveness among adults aged 60 or more years. Methods: The PREDIDEP study is a 2-year multicentre, randomized, single-blinded nutritional trial. At baseline and at 1-year and 2-year follow-up, SF-36 health survey questionnaire was collected to evaluate participants' HRQoL (total and specific range for each of the 8 dimensions: 0 to 100 points). Mixed effect linear models were used to assess changes in HRQoL according to adherence to the Mediterranean diet. The trial was registered at ClinicalTrials.gov NCT03081065. Results: After 2 years of intervention, the Mediterranean Diet intervention group compared to control group (without nutritional intervention, only usual clinical care) showed an improvement in some dimensions of HRQoL such as Mental Health (7.22; 95 % CI = 2.22–12.22) (between-group difference: 6.79; 95 % CI − 0.14–13.73, p = 0.055); Vitality (9.51; 95 % CI = 4.00–15.03) (between-group difference: 9.00; 95 % CI 1.75–16.25, p = 0.020); Mental Summary Component (2.83; 95 % CI = 0.55–5.11) (between-group difference: 1.17; 95 % CI = − 1.96–4.30, p = 0.462); and General Health (10.70; 95 % CI = 5.58–15.81) (between-group difference: 6.20; 95 % CI = − 0.89–13.28, p = 0.086). Similar results were observed for participants aged 60 or more years. Conclusion: The intervention based on Mediterranean diet in patients with previous depression seems to be effective in improving HRQoL, especially the mental dimensions. This effect is also observed among participants aged 60 or more years.This study was externally funded by the Spanish Ministry of Science and Innovation (Carlos III National Health Institute-ISCIII), PI16/01274

Establishment of a screening platform based on human coronavirus OC43 for the identification of microbial natural products with antiviral activity

Human coronaviruses (HCoVs) cause respiratory tract infections and are of great importance due to the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Human betacoronavirus OC43 (HCoV-OC43) is an adequate surrogate for SARS-CoV-2 because it infects the human respiratory system, presents a comparable biology, and is transmitted in a similar way. Its use is advantageous since it only requires biosafety level (BSL)-2 infrastructure which minimizes costs and biosafety associated limitations. In this report, we describe a high-throughput screening (HTS) platform to identify compounds that inhibit the propagation of HCoV-OC43. Optimization of assays based on inhibition of the cytopathic effect and virus immunodetection with a specific antibody, has provided a robust methodology for the screening of a selection of microbial natural product extracts from the Fundación MEDINA collection. Using this approach, a subset of 1280 extracts has been explored. Of these, upon hit confirmation and early LC-MS dereplication, 10 extracts were identified that contain potential new compounds. In addition, we report on the novel antiviral activity of some previously described natural products whose presence in bioactive extracts was confirmed by LC/MS analysis.This work was funded by the the European Commission—Next Generation EU (regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global), the Instituto de Salud Carlos III Subdirección General de Redes y Centros de Investigación Cooperativa-Red de Investigación Cooperativa en Enfermedades Tropicales (RICET: RD16/0027/0014), the MCIN/AEI/10.13039/501100011033 (PID2019-109623RB-I00), the MCIN/AEI/10.13039/501100011033 and FEDER Una manera de hacer Europa (2016-79957-R) and by the Junta de Andalucía (BIO-199)N

PPARGC1A gene promoter methylation as a biomarker of insulin secretion and sensitivity in response to glucose challenges

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose