Key points
Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as ...chronodisruption, with effects even when this occurs during pregnancy.
Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function.
We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels.
The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases.
Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long‐term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down‐regulated and 437 up‐regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48–20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long‐term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.
Key points
Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy.
Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function.
We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels.
The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases.
The rat fetal adrenal contains an autonomous circadian clock, potentially regulated by maternal melatonin.
The adrenal gland in the adult is a peripheral circadian clock involved in the coordination ...of energy intake and expenditure, required for adaptation to the external environment. During fetal life, a peripheral circadian clock is present in the nonhuman primate adrenal gland. Whether this extends to the fetal adrenal gland like the rat is unknown. Here we explored in vivo and in vitro whether the rat fetal adrenal is a peripheral circadian clock entrained by melatonin. We measured the 24-h changes in adrenal content of corticosterone and in the expression of clock genes Per-2 and Bmal-1 and of steroidogenic acute regulatory protein (StAR), Mt1 melatonin receptor, and early growth response protein 1 (Egr-1) expression. In culture, we explored whether oscillatory expression of these genes persisted during 48 h and the effect of a 4-h melatonin pulse on their expression. In vivo, the rat fetal adrenal gland showed circadian expression of Bmal-1 and Per-2 in antiphase (acrophases at 2200 and 1300 h, respectively) as well as of Mt1 and Egr-1. This was accompanied by circadian rhythms of corticosterone content and of StAR expression both peaking at 0600 h. The 24-h oscillatory expression of Bmal-1, Per-2, StAR, Mt1, and Egr-1 persisted during 48 h in culture; however, the antiphase between Per-2 and Bmal-1 was lost. The pulse of melatonin shifted the acrophases of all the genes studied and restored the antiphase between Per-2 and Bmal-1. Thus, in the rat, the fetal adrenal is a strong peripheral clock potentially amenable to regulation by maternal melatonin.
Summary
Lepidium meyenii, known as maca, is a popular nutraceutical food which is grown over 4,000 m above sea level in the Peruvian central highlands. Maca contains alkaloids, but there are no ...studies on their biological effects. The butanol fraction obtained from methanol extract of maca hypocotyls contains alkaloids. The effects of butanol/aqueous fractions partitioned from methanol extract of yellow and black maca were examined. Total phenolic content (TPC) and antioxidant capacity by 2,2′‐diphenyl‐1‐picrylhydrazyl were used to evaluate maca fractions in vitro. Daily sperm production and sperm count in epididymis and vas deferens in mice were determined as biological effect of maca extracts in vivo. Yellow maca (21.7%±0.69) had better antioxidant capacity than black maca (18.2% ± 0.12; p < .01). Antioxidant activity was better in the methanolic fraction than in the aqueous fraction of yellow or black maca. TPC is higher in the aqueous fraction than in the methanolic extract of yellow or black maca. Black maca administration resulted in higher concentration of sperm count in epididymis and vas deferens compared to yellow maca. A higher biological effect was observed in methanolic extract and in aqueous extract than in the butanol fraction of maca. In conclusion, better biological effect was observed in the methanolic extract of maca than in its partitioned fractions.
In the adult mammal the circadian system, which allows predictive adaptation to daily environmental changes, comprises peripheral oscillators in most tissues, commanded by the suprachiasmatic nucleus ...(SCN) of the hypothalamus. The external environment of the fetus is provided by its mother. In primates, maternal melatonin is a candidate to entrain fetal circadian rhythms, including the SCN rhythms of metabolic activity. We found in the 90% of gestation capuchin monkey fetus expression of the clock genes Bmal-1, Per-2, Cry-2, and Clock in the SCN, adrenal, pituitary, brown fat, and pineal. Bmal-1, Per-2, and the melatonin 1 receptor (MT1) showed a robust oscillatory expression in SCN and adrenal gland, whereas a circadian rhythm of dehydroepiandrosterone sulphate was found in plasma. Maternal melatonin suppression changed the expression of Bmal-1, Per-2, and MT1 in the fetal SCN. These effects were reversed by maternal melatonin replacement. In contrast, neither maternal melatonin suppression nor its replacement had effects on the expression of Per-2 and Bmal-1 or MT1 in the fetal adrenal gland or the circadian rhythm of fetal plasma dehydroepiandrosterone sulphate. Our data suggest that maternal melatonin is a Zeitgeber for the fetal SCN but probably not for the adrenal gland.
In nonhuman primates and rodents, melatonin acting directly on the adrenal gland, inhibits glucocorticoid response to ACTH. In these species, an intrinsic adrenal circadian clock is involved in ...ACTH-stimulated glucocorticoid production. We investigated whether these findings apply to the human adrenal gland by determining i) expression of clock genes in vivo and ii) direct effects of melatonin in ACTH-stimulated adrenal explants over a) expression of the clock genes PER1 (Period 1) mRNA and BMAL1 Brain-Muscle (ARNT)-like protein, ACTH-induced steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase (3β-HSD) and b) over cortisol and progesterone production. Adrenal tissue was obtained from 6 renal cancer patients undergoing unilateral nephrectomy-adrenalectomy. Expression of the clock genes PER1, PER2, CRY2 (Cryptochrome 2), CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1, was investigated by RT-PCR in a normal adrenal and in an adenoma. In independent experiments, explants from 4 normal adrenals were preincubated in culture medium (6 h) followed by 12 h in: medium alone; ACTH (100 nM); ACTH plus melatonin (100 nM); and melatonin alone. The explants' content of PER1 mRNA (real-time PCR) and StAR, 3β-HSD, BMAL1 (immuno slot-blot), and their cortisol and progesterone production (RIA) were measured. The human adrenal gland expresses the clock genes PER1, PER2, CRY2, CLOCK, and BMAL1. ACTH increased PER1 mRNA, BMAL1, StAR, and 3β-HSD protein levels, and cortisol and progesterone production. Melatonin inhibited these ACTH effects. Our study demonstrates, for the first time, direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland.
According to the World Health Organization, Salmonella is one of the most important zoonotic foodborne pathogens. Poultry products are thought to be the main source of Salmonella, which means that it ...is necessary to control Salmonella at the pre-harvest stage. Bacteriophages, acting as host-specific parasites of bacterial cells, represent one of the alternatives to antibiotics that can contribute to food safety and security. The present study evaluated the effectiveness of the bacteriophage cocktail SalmoFREE® to control Salmonella on a commercial broiler farm. We assessed the relationship between the use of SalmoFREE® and productivity parameters (feed conversion, weight gain, homogeneity). Two field trials (trial 1 n = 34,986; trial 2 n = 34,680) were carried out under commercial rearing conditions on a Colombian broiler farm with a record of Salmonella presence. Each trial comprised 2 control chicken houses and 2 experimental ones. SalmoFREE® and a control suspension were delivered in the drinking water at 3 time points in the production cycle, and the presence of Salmonella was assessed in cloacal swabs the day before and after the treatments. Results revealed that SalmoFREE® controls the incidence of Salmonella and does not affect the animals nor the production parameters, demonstrating its efficacy and innocuity at the production scale. We detected phage-specific genes in samples of total DNA extracted from ceca after the treatment with SalmoFREE®, and tested for the appearance of cocktail-resistant Salmonella, which showed to be an uncommon event. These results contribute relevant information to the adoption of phage therapy as an alternative to growth-promoter antibiotics on poultry farms.
This article introduces a novel Induction Blade (IB) prototype modeled by Blade Element Momentum (BEM) theory, which develops higher torque during the starting phase for Horizontal Axis Wind Turbines ...(HAWT), especially for micro-turbines. The IB is composed of two parallel blades joined at their tips and roots, forming a distinctive hole in the space between the blades that generates a Venturi effect as air passes through. This phenomenon in the IB hole together with the extra lift generated by the area of the second blade produce extra valuable torque during the starting phase. We used Computational Fluid Dynamics (CFD) analysis to evaluate the aerodynamic properties of this design compared with a traditional blade design of the same radius. The IB and traditional prototypes were built (50W, diameter 0.62m, λ=9 and at speed rated 8m/s) by additive manufacturing in a 3D printer and their aerodynamic behaviors tested in a small wind tunnel (square section 0.7m x 0.7m). Our results using CFD analysis show that this novel IB produces up to 65% extra torque without losing output power for low wind velocity (5-8 m/s). IMPI (Mexican Institute of Industrial Protection) protects this prototype shape.
The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the ...circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.
For people with type 1 diabetes, there are limited evidence-based resources to support self-management when traveling across multiple time zones. Here, we compared glycemic control on insulin ...degludec versus glargine U100 as the basal insulin for adults using multiple daily injections (MDI) while traveling across multiple time zones.
This randomized crossover pilot study compared insulin degludec versus glargine U100 for adults with type 1 diabetes using MDI insulin during long-haul travel to and from Hawaii to New York. Insulin degludec was administered daily at the same time regardless of time zone, and glargine was administered per travel algorithm. Primary end point was the percentage of time in range (TIR) between 70 and 140 mg/dL during the initial 24 h after each direction of travel. Secondary end points included standard continuous glucose monitoring metrics, jet lag, fatigue, and sleep.
The study enrolled 25 participants (56% women, mean ± SD age of 35 ± 14.5 years, HbA1c of 7.4 ± 1.2% 57 ± 13.1 mmol/mol, and diabetes duration of 20.6 ± 15 years). There was no significant difference in glycemic outcomes between the two arms of the study, including TIR, hypoglycemia, or hyperglycemia. Neither group achieved >70% TIR 70-180 mg/dL during travel. Jet lag was greater on glargine U100 in eastward travel but not westward. Fatigue was greater after westward travel on glargine. Sleep was not significantly different between basal insulins.
In adults with type 1 diabetes using MDI of insulin and traveling across multiple time zones, glycemic outcomes were similar comparing insulin degludec and glargine U100.
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