Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable ...intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non‐communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non‐communicable chronic diseases are associated with early‐life adaptations that produce long‐term dysfunction. Early‐life environment sets the long‐term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling‐related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or early childhood, to re‐set the metabolic homeostasis and break the chain of subsequent events that could lead to the development of disease.
Unlabelled data appear in many domains and are particularly relevant to streaming applications, where even though data is abundant, labelled data is rare. To address the learning problems associated ...with such data, one can ignore the unlabelled data and focus only on the labelled data (supervised learning); use the labelled data and attempt to leverage the unlabelled data (semi-supervised learning); or assume some labels will be available on request (active learning). The first approach is the simplest, yet the amount of labelled data available will limit the predictive performance. The second relies on finding and exploiting the underlying characteristics of the data distribution. The third depends on an external agent to provide the required labels in a timely fashion. This survey pays special attention to methods that leverage unlabelled data in a semi-supervised setting. We also discuss the delayed labelling issue, which impacts both fully supervised and semi-supervised methods. We propose a unified problem setting, discuss the learning guarantees and existing methods, and explain the differences between related problem settings. Finally, we review the current benchmarking practices and propose adaptations to enhance them.
During the early post-natal period, offspring are vulnerable to environmental insults, such as nutritional and hormonal changes, which increase risk to develop metabolic diseases later in life. Our ...aim was to understand whether maternal obesity during lactation programs offspring to metabolic syndrome and obese phenotype, in addition we aimed to assess the peripheral glucose metabolism and hypothalamic leptin/insulin signaling pathways. At delivery, female Wistar rats were randomly divided in two groups: Control group (CO), mothers fed a standard rodent chow (Nuvilab); and Diet-induced obesity group (DIO), mothers who had free access to a diet performed with 33% ground standard rodent chow, 33% sweetened condensed milk (Nestlé), 7% sucrose and 27% water. Maternal treatment was performed throughout suckling period. All offspring received standard rodent chow from weaning until 91-day-old. DIO dams presented increased total body fat and insulin resistance. Consequently, the breast milk from obese dams had altered composition. At 91-day-old, DIO offspring had overweight, hyperphagia and higher adiposity. Furthermore, DIO animals had hyperinsulinemia and insulin resistance, they also showed pancreatic islet hypertrophy and increased pancreatic β-cell proliferation. Finally, DIO offspring showed low ObRb, JAK2, STAT-3, IRβ, PI3K and Akt levels, suggesting leptin and insulin hypothalamic resistance, associated with increased of hypothalamic NPY level and decreased of POMC. Maternal obesity during lactation malprograms rat offspring to develop obesity that is associated with impairment of melanocortin system. Indeed, rat offspring displayed glucose dyshomeostasis and both peripheral and central insulin resistance.
To evaluate the influence of dimethyl sulfoxide (DMSO) solutions used as dentin pretreatments on microtensile bond strength (µTBS), as well as the dentin/restoration interface micromorphology of a ...universal adhesive in etch-and-rinse or self-etch mode.
Eighty blocks of dentin were submitted to acid conditioning with 35% phosphoric acid (etch-and-rinse), or not (self-etch), and distributed among the treatments (n = 10): CON: Scotchbond Universal/3M Oral Care; DMSO: pretreatment with DMSO; DMSO/water: pretreatment with DMSO in water (1:1); DMSO/ethanol: pretreatment with DMSO in ethanol (1:1). Microtensile bond strength and failure tests were performed after 24-h and 6-month storage. The tooth-restoration interface was evaluated using scanning electron microscopy to assess the hybrid layer formed.
The interaction between treatments, storage time, and etching modes was not significant for µTBS (p = 0.2469). The DMSO, DMSO/water and DMSO/ethanol pretreatments did not affect µTBS values at either time point (p = 0.8732). Aging decreased µTBS over time only for the etch-and-rinse strategy, although the groups presented higher microtensile bond strengths in etch-and-rinse mode than in self-etch mode at both time points (p < 0.0001). The micromorphological images of the interface showed that different DMSO pretreatment solutions did not impair hybrid layer formation.
The use of dentin pretreatments containing DMSO did not improve the bonding or the micromorphology of a universal adhesive in etch-and-rinse or self-etch modes.
The Role of Astrocytes in the Neurorepair Process Chiareli, Raphaela Almeida; Carvalho, Gustavo Almeida; Marques, Bruno Lemes ...
Frontiers in cell and developmental biology,
05/2021, Letnik:
9
Journal Article
Recenzirano
Odprti dostop
Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, ...the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Thus, reactive astrocytes release several signaling molecules that modulates and contributes to the defense against injuries and infection in the central nervous system. Therefore, deciphering the complex signaling pathways of reactive astrocytes after brain damage can contribute to the neuroinflammation control and reveal new molecular targets to stimulate neurorepair process. In this review, we present the current knowledge about the role of astrocytes in brain damage and repair, highlighting the cellular and molecular bases involved in synaptogenesis and neurogenesis. In addition, we present new approaches to modulate the astrocytic activity and potentiates the neurorepair process after brain damage.
Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In ...this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO
achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (p
< 0.0001) and -off (p
< 0.01). Exercise increased BAT temperature in lights-on (p
< 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (p
< 0.05), β3-AR (p
< 0.001), and UCP1 (p
< 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (p
< 0.0001) with greater effect in increasing UCP1 (p
< 0.001) and increased β3-AR (p
< 0.001) content.
Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased β3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.
Nutritional disturbances during the early postnatal period can have long-lasting effects on neurodevelopment and may be related to behavioural changes at adulthood. While such neuronal connection ...disruption can contribute to social and behaviour alterations, the dysregulation of the neuroendocrine pathways involved in nutrient-sensing balance may also cause such impairments, although the underlying mechanisms are still unclear. We aimed to evaluate sex-specific neurodevelopmental and behavioural changes upon postnatal overfeeding and determine the potential underpinning mechanisms at the central nervous system level, with a focus on the interconnection between synaptic and neuroendocrine molecular alterations. At postnatal day 3 (PND3) litters were culled to three animals (small litter procedure). Neurodevelopmental tests were conducted at infancy, whereas behavioural tests to assess locomotion, anxiety, and memory were performed at adolescence, together with molecular analysis of the hippocampus, hypothalamus, and prefrontal cortex. At infancy, females presented impaired acquisition of an auditory response, eye opening, olfactory discrimination, and vestibular system development, suggesting that female offspring neurodevelopment/maturation was deeply affected. Male offspring presented a transitory delay in locomotor performance., while both offspring had lower upper limb strength. At adolescence, both sexes presented anxious-like behaviour without alterations in short-term memory retention. Both males and females presented lower NPY1R levels in a region-specific manner. Furthermore, both sexes presented synaptic changes in the hippocampus (lower GABAA in females and higher GABAA levels in males), while, in the prefrontal cortex, similar higher GABAA receptor levels were observed. At the hypothalamus, females presented synaptic changes, namely higher vGLUT1 and PSD95 levels. Thus, we demonstrate that postnatal overfeeding modulates offspring behaviour and dysregulates nutrient-sensing mechanisms such as NPY and GABA in a sex- and brain-region-specific manner.
Obesogenic environments such as Westernized diets, overnutrition, and exposure to glycation during gestation and lactation can alter peripheral neuroendocrine factors in offspring, predisposing for ...metabolic diseases in adulthood. Thus, we hypothesized that exposure to obesogenic environments during the perinatal period reprograms offspring energy balance mechanisms. Four rat obesogenic models were studied: maternal diet-induced obesity (DIO); early-life obesity induced by postnatal overfeeding; maternal glycation; and postnatal overfeeding combined with maternal glycation. Metabolic parameters, energy expenditure, and storage pathways in visceral adipose tissue (VAT) and the liver were analyzed. Maternal DIO increased VAT lipogenic NPY receptor-1 (NPY1R), NPY receptor-2 (NPY2R), and ghrelin receptor, but also lipolytic/catabolic mechanisms dopamine-1 receptor (D1R) and p-AMP-activated protein kinase (AMPK) in male offspring, while reducing NPY1R in females. Postnatally overfed male animals only exhibited higher NPY2R levels in VAT, while females also presented NPY1R and NPY2R downregulation. Maternal glycation reduces VAT expandability by decreasing NPY2R in overfed animals. Regarding the liver, D1R was decreased in all obesogenic models, while overfeeding induced fat accumulation in both sexes and glycation the inflammatory infiltration. The VAT response to maternal DIO and overfeeding showed a sexual dysmorphism, and exposure to glycotoxins led to a thin-outside-fat-inside phenotype in overfeeding conditions and impaired energy balance, increasing the metabolic risk in adulthood.
Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult ...offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted IUPR) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.
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