Engineering Organoids for in vitro Modeling of Phenylketonuria

Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Severe cognitive and neuronal impairment are observed in untreated/late-diagnosed patients, and even early treated ones are not safe from life-long sequelae. Despite the wealth of knowledge acquired from available disease models, the chronic effect of Phenylketonuria in the brain is still poorly understood and the consequences to the aging brain remain an open question. Thus, there is the need for better predictive models, able to recapitulate specific mechanisms of this disease. Human induced pluripotent stem cells (hiPSCs), with their ability to differentiate and self-organize in multiple tissues, might provide a new exciting in vitro platform to model specific PKU-derived neuronal impairment. In this review, we gather what is known about the impact of phenylalanine in the brain of patients and highlight where hiPSC-derived organoids could contribute to the understanding of this disease.

Hypothalamic regulation of reproduction under the chronic influence of toluene and melatonin

Experiments on chronic administration of melatonin with and without chronic inhalation of toluene dosed at both maximal permissible concentration (50 mg/ml) and limited chronical range (500 mg/m3) have been carried out on female rats to discover their effects on biogenic amines system in hypothalamic structures related to gonadoliberin synthesis and secretion - preoptic area (PA) and median eminence (ME). Contents of biogenic amines in ME and especially in PA have been shown to have circadian variations with maximum in the morning in control group of rats.The chronic effect of synchronizing agent melatonin (administered dissolved in drinking water in concentration of 10 pg/m l, at night during 2 months) on neotransmitters and their circadian variations in both hypothalamic structures proved surprisingly to be much alike the effect of toluene. Both chemicals cause the disturbances of normal circadian variations o f norepinephrine, dopamine and serotonine in PA and dopamine in ME. The simultaneous administration of toluene and melatonin showed likewise no synchronizing ability of the latter under the conditions described.

A Novel Hypothalamic Factor, Neurosecretory Protein GM, Causes Fat Deposition in Chicks

We recently discovered a novel cDNA encoding the precursor of a small secretory protein, neurosecretory protein GM (NPGM), in the mediobasal hypothalamus of chickens. Although our previous study showed that subcutaneous infusion of NPGM for 6 days increased body mass in chicks, the chronic effect of intracerebroventricular (i.c.v.) infusion of NPGM remains unknown. In this study, chronic i.c.v. infusion of NPGM for 2 weeks significantly increased body mass, water intake, and the mass of abdominal fat in chicks, whereas NPGM did not affect food intake, muscle mass, or blood glucose concentration. Morphological analyses revealed that fat accumulation occurred in both liver and abdominal fat. These results indicate that NPGM may participate in fat storage in chicks.

Temperature and Aging Affect Glyphosate Toxicity and Fatty Acid Composition in Allonychiurus kimi (Lee) (Collembola)

Glyphosate is the most used herbicide worldwide, but enormous use of glyphosate has raised concerned about its environmental loadings. Although glyphosate is considered non-toxic, toxicity data for soil non-target organisms according to temperature and aging are scarce. This study examined the toxicity of glyphosate with the temperature (20 °C and 25 °C) and aging times (0 day and 7 days) in soil using a collembolan species, Allonychiurus kimi (Lee). The degradation of glyphosate was investigated. Fatty acid composition of A. kimi was also investigated. The half-life of glyphosate was 2.38 days at 20 °C and 1.69 days at 25 °C. At 20 °C with 0 day of aging, the EC50 was estimated to be 93.5 mg kg−1. However, as the temperature and aging time increased, the glyphosate degradation increased, so no significant toxicity was observed on juvenile production. The proportions of the arachidonic acid and stearic acid decreased and increased with the glyphosate treatment, respectively, even at 37.1 mg kg−1, at which no significant effects on juvenile production were observed. Our results showed that the changes in the glyphosate toxicity with temperature and aging time were mostly dependent on the soil residual concentration. Furthermore, the changes in the fatty acid compositions suggest that glyphosate could have a chronic effect on soil organisms.

Comparative Study of the Biochemical Response Behavior of Some Highly Toxic Minerals on Selenosis in Rats

Many researchers have studied the metabolism of toxics including selenium (Se) in biological medium in rats and defined some correlations between selenium and other minerals as arsenic (As), cadmium (Cd), mercury (Hg), and thallium (Tl). An investigation of the potential influences of As, Hg, Tl and Pb on Se metabolism, which can suggest new drugs to cope the poisonousness of Se. The current study also has looked into the potential use of As(III)/As(V) toxic in the treatment of essential mineral Se in the animals (as rats) based on sequestration of these toxic elements into biologically inert complexes, reflecting the enormous interest in this subject. The acute studies have been initially achieved by shaping the pulmonary and biliary excretions of the volatile Se in neonatal masculine Holtzman rats which were injected with selenite subcutaneously in the hind flank, then the volatile Se was trapped in 8N HNO3 and the radioselenate detected in a scintillation counter. The chronic cases were carried out with the nursing of rats with a purified diet of water-soluble vitamin mix, fat-soluble vitamin mix, saccharides, oil, and salts. One week after the basic diet, the rats taken Se have received diets containing 10 ppm of the element as sodium selenite (Na2SeO3) or selenate (Na2SeO4) added in the salts. The calorimeter was used to analyze Se in the frozen tissue specimens. As, Hg, and Tl were repressed the volatized Se excreted from the lungs. As has assisted the biliary excretion of Se and inhibited the chronic selenosis. Tl has increased the retention of Se in the liver and kidney, but, had no chronic effect on the amount of Se deposited in all the studied tissues. Similarly, Hg has increased the retention of Se but in the spleen and carcass of rats indicating to the high Se concentration in blood. Hg and Tl have inhibited the Se in urine. No effects of the doses rich in As, Hg, and Tl on the Se excretion in fecal. Even though, we suggest As as a possible medication to chronic selenosis.

The effects of interval training on peripheral brain derived neurotrophic factor (BDNF) in young adults: a systematic review and meta-analysis

The aim of the current meta-analysis was to determine the effects of acute and chronic interval training (IT) on serum and plasma BDNF concentrations in healthy young adults. A literature search was performed using six databases until February 2020. The TESTEX scale was used to assess the quality of studies. Effect sizes (ES) were computed and two-tailed α values < 0.05 and non-overlapping 95% confidence intervals (95% CI) were considered statistically significant. Heterogeneity, inconsistency (I2), and small-study effects using the Luis Furuya–Kanamori (LFK) index were examined. Fifteen studies (n = 277 participants, age = 24 ± 3 years) were included. The overall effects of IT on circulating BDNF concentrations were moderate and significant (ES = 0.62, 95% CI 0.00, 1.24, heterogeneous (p < 0.001), highly inconsistent (I2 = 90%), and with major asymmetry (LFK index = 2.76). The acute effect of IT on peripheral BDNF levels was large and significant (ES = 1.10, 95% CI 0.07, 2.14), heterogeneous (p < 0.001), highly inconsistent (I2 = 92%), and with major asymmetry (LFK index = 3.34). The chronic effect of IT on circulating BDNF was large and significant (ES = 0.93, 95% CI 0.40, 1.46), heterogeneous (p < 0.001), with moderate inconsistency (I2 = 70%), and minor asymmetry (LFK index = 1.21). Acute and chronic IT elicited a moderate increase in serum and plasma BDNF concentrations in a healthy young population.