Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies.

Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of "clock genes" and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.

Ecotoxicity evaluation of polymeric nanoparticles loaded with ascorbic acid for fish nutrition in aquaculture.

BACKGROUND: Ascorbic acid (AA) is a micronutrient essential for the mechanisms of reproduction, growth, and defense in fish. However, the biosynthesis of this micronutrient does not occur in fish, so it must be supplied with food. A difficulty is that plain AA is unstable, due to the effects of light, high temperature, and oxygen, among others. The use of nanoencapsulation may provide protection and preserve the physicochemical characteristics of AA for extended periods of time, decreasing losses due to environmental factors. METHOD: This study evaluated the protective effect of nanoencapsulation in polymeric nanoparticles (chitosan and polycaprolactone) against AA degradation. Evaluation was made of the physicochemical stability of the nanoformulations over time, as well as the toxicological effects in zebrafish (Danio rerio), considering behavior, development, and enzymatic activity. For the statistical tests, ANOVA (two-way, significance of p < 0.05) was used. RESULTS: Both nanoparticle formulations showed high encapsulation efficiency and good physicochemical stability during 90 days. Chitosan (CS) and polycaprolactone (PCL) nanoparticles loaded with AA had mean diameters of 314 and 303 nm and polydispersity indexes of 0.36 and 0.28, respectively. Both nanosystems provided protection against degradation of AA exposed to an oxidizing agent, compared to plain AA. Total degradation of AA was observed after 7, 20, and 480 min for plain AA, the CS nanoparticle formulation, and the PCL nanoparticle formulation, respectively. For zebrafish larvae, the LC50 values were 330.7, 57.4, and 179.6 mg/L for plain AA, the CS nanoparticle formulation, and the PCL nanoparticle formulation, respectively. In toxicity assays using AA at a concentration of 50 mg/L, both types of nanoparticles loaded with AA showed lower toxicity towards the development of the zebrafish, compared to plain AA at the same concentration. Although decreased activity of the enzyme acetylcholinesterase (AChE) did not affect the swimming behavior of zebrafish larvae in the groups evaluated, it may have been associated with the observed morphometric changes, such as curvature of the tail. CONCLUSIONS: This study showed that the use of nanosystems is promising for fish nutritional supplementation in aquaculture. In particular, PCL nanoparticles loaded with AA seemed to be most promising, due to higher protection against AA degradation, as well as lower toxicity to zebrafish, compared to the chitosan nanoparticles. The use of nanotechnology opens new perspectives for aquaculture, enabling the reduction of feed nutrient losses, leading to faster fish growth and improved sustainability of this activity.

Zein Nanoparticles Impregnated with Eugenol and Garlic Essential Oils for Treating Fish Pathogens.

The supply of food derived from aquaculture has increased significantly in recent years. The aim of this industrial sector is to produce sustainable products to meet the needs of consumers, providing food security and nutritional benefits. The development of aquaculture has faced challenges including disease outbreaks that can cause substantial economic losses. These diseases can be controlled using chemicals such as antibiotics. However, the indiscriminate use of these substances can have major negative impacts on human health and the environment with the additional risk of the emergence of resistant organisms. The present manuscript describes the use of phytotherapy in association with nanotechnology in order to obtain a more effective and less harmful system for the control of bacterial diseases in fish. Zein nanoparticles associated with eugenol and garlic essential oil were prepared through antisolvent precipitation and characterized. Zein nanoparticles are promising carrier systems as zein proteins are biodegradable and biocompatible and, in this way, good candidates for encapsulation of active ingredients. The system presented good physicochemical properties with an average particle diameter of approximately 150 nm, a polydispersity index lower than 0.2, and a zeta potential of approximately 30 mV. High encapsulation efficiency was obtained for the active compounds with values higher than 90%, and the compounds were protected against degradation during storage (90 days). The nanoparticle formulations containing the botanical compounds also showed less toxicity in the tests performed with a biomarker (Artemia salina). In addition, the systems showed bactericidal activity against the important fish pathogenic bacteria Aeromonas hydrophila, Edwardsiella tarda, and Streptococcus iniae in vitro. The present study opens new perspectives for the use of botanical compounds in combination with nanotechnology to treat fish diseases caused by bacteria, contributing to a more sustainable fish chain production.

Niveles de lípidos sanguíneos en escolares chilenos de 10 a 14 años de edad / Blood lipids in chilean children 10-14 years of age

Introducción: Las concentraciones de lípidos sanguíneos en niños y adolescentes se evalúan utilizando referencias internacionales. Objetivos: Describir las concentraciones de lípidos sanguíneos en una población de escolares chilenos y compararlas con la referencia más utilizada (Lipid Research Clinics Program) además de los puntos de corte recomendados en 2011. Métodos: Estudio transversal en 3.325 escolares de 10 a 14 años de edad. Se realizó antropometría, auto-reporte de desarrollo puberal y medición en ayunas de colesterol total (CT), colesterol unido a lipoproteínas de alta densidad (CHDL) y triglicéridos (TG). El colesterol unido a lipoproteínas de baja densidad (CLDL) se calculó con fórmula de Friedewald. Se realizó descripción, regresión múltiple y estudio de concordancia. Resultados: Se incluyeron 3.063 niños de 11,4 ± 0,9 años de edad, 53% mujeres, 20,9% pre-púberes; 22,6% con sobrepeso y 15,8% con obesidad. Los promedios fueron: CT: 159,2 ± 28,3, CHDL: 51,9 ± 12,1, LDL: 89,0 ± 31,5 y TG: 93,2 ± 60 mg/dL. Los hombres tuvieron mayor CHDL: 53,3 ± 12,2 vs 50,6 ± 11,8 mg/dL y menor TG: 86,2 ± 58,2 vs 99,5 ± 61,7 mg/dL que las mujeres (p < 0,001). Con regresión múltiple se encontró influencia del estado nutricional y edad en todos los lípidos y del sexo en la mayoría. Comparados con la referencia hubo concordancia en CT y CLDL, pero los niños chilenos presentaron mayores niveles de TG sobre el percentil 50 y menores niveles de CHDL bajo percentil 50. Conclusiones: Las concentraciones de lípidos sanguíneos estuvieron influidas por el estado nutricional, edad y sexo. En comparación a la referencia, se encontró un patrón de mayor riesgo cardiovascular en los niños chilenos (AU)

INTRODUCTION AND OBJECTIVES: Plasma lipid levels in children and adolescents are evaluated with international references. The objective was to describe them in Chilean students, to compare them with the most used reference (Lipids Research Clinics Program) and the cut-off points recommended in 2011.METHODS:Cross-sectional study in 3325 children, 10 to 14 years of age. Anthropometry and auto-report of pubertal development were performed. A 12 hours fast blood sample was taken to measure total (TC), highdensity lipoprotein cholesterol (HDLC) and triglycerides (TG). Low-density lipoprotein cholesterol (LDLC) was calculated with Friedewald formula. Variables were described, Hochberg test for multiple comparisons and stepwise lineal regression were applied. The degree of agreement between local percentiles and the two international references was studied. RESULTS: We studied 3,063 children, 11.4 ± 0.9 years old, 53% girls, 20.9% pre-pubertal, 22.6% had overweight, and 15.8% obesity. Averages: TC: 159.2 ± 28.3, HDLC: 51.9 ± 12.1, LDLC: 89.0 ± 31.5 and TG: 93.2 ± 60 mg/dL. Boys had higher HDLC: 53.3 ± 12.2 vs. 50.6 ± 11.8 mg/dL and lower TG: 86.2 ± 58.2 vs. 99.5 ± 61.7 mg/dL than girls (p < 0,001). Influences of nutritional status, sex and age were significant. We founded high agreement with the reference for TC and LDLC, but HDLC levels were lower and TG were higher, for their cut-off points: percentiles 10th and 95th, respectively. CONCLUSIONS: Blood lipids were influenced by nutritional status, sex and age. Percentile values were comparable to the international reference except for HDLC and TG, showing a more atherogenic pattern (AU)