RESUMO

Worldwide, diabetes mellitus represents a growing health problem. If it occurs during pregnancy, it can increase the risk of various abnormalities in early and advanced life stages of exposed individuals due to fetal programming occurring in utero. Studies have determined that maternal conditions interfere with the genotypes and phenotypes of offspring. Researchers are now uncovering the mechanisms by which epigenetic alterations caused by diabetes affect the expression of genes and, therefore, the development of various diseases. Among the numerous possible epigenetic changes in this regard, the most studied to date are DNA methylation and hydroxymethylation, as well as histone acetylation and methylation. This review article addresses critical findings in epigenetic studies involving diabetes mellitus, including variations reported in the expression of specific genes and their transgenerational effects.

RESUMO

Thallium (Tl) is a toxic heavy metal responsible for noxious effects in living organisms. As a pollutant, Tl can be found in the environment at high concentrations, especially in industrial areas. Systemic toxicity induced by this toxic metal can affect cell metabolism, including redox alterations, mitochondrial dysfunction, and activation of apoptotic signaling pathways. Recent focus on Tl toxicity has been devoted to the characterization of its effects at the nuclear level, with emphasis on DNA, which, in turn, may be responsible for cytogenetic damage, mutations, and epigenetic changes. In this work, we review and discuss past and recent evidence on the toxic effects of Tl at the systemic level and its effects on DNA. We also address Tl's role in cancer and its control.

RESUMO

Aluminum chlorohydrate (ACH) is a major aerosol component frequently used as the active ingredient in antiperspirants, and in vivo studies have raised a concern about its inhalation toxicity. Still, few studies have addressed its effects on the human respiratory tract. Therefore, we developed a study on ACH inhalation toxicity using an in vitro human alveolar cell model (A549 cells) with molecular and cellular markers of oxidative stress, immunotoxicity, and epigenetic changes. The chemical characterization of ACH suspensions indicated particle instability and aggregation; however, side-scatter analysis demonstrated significant particle uptake in cells exposed to ACH. Exposure of A549 cells to non-cytotoxic concentrations of ACH (0.25, 0.5, and 1 mg/ml) showed that ACH induced reactive oxygen species. Moreover, ACH upregulated TNF, IL6, IL8, and IL1A genes, but not the lncRNAs NEAT1 and MALAT1. Finally, no alterations on the global DNA methylation pattern (5-methylcytosine and 5-hydroxymethylcytosine) or the phosphorylation of histone H2AX (γ-H2AX) were observed. Our data suggest that ACH may induce oxidative stress and inflammation on alveolar cells, and A549 cells may be useful to identify cellular and molecular events that may be associated with adverse effects on the lungs. Still, further research is needed to ensure the inhalation safety of ACH.

Assuntos

RESUMO

ABSTRACT Systemic lupus erythematosus is an autoimmune disease that involves several systems, affects mainly young adult women, and causes a significant deterioration in quality of life. Different environmental aspects are known to facilitate the development of lupus in predisposed individuals. For several years it has been known that factors such as exposure to UV rays are related to the development of lupus; however, due to factors inherent to globalization, life-style changes, improved knowledge of cell signaling pathways as well as a better understanding of metabolomics, proteomics an genomics, it has been possible to better understand the relationship between cells and their environment. This study based on a narrative review, compiles the existing evidence on different risk factors and the development of lupus, including aspects typical of the Colombian population.

RESUMEN El lupus eritematoso sistémico es una enfermedad autoinmune que compromete diferentes sistemas, afecta principalmente a mujeres adultas jóvenes y genera un deterioro significativo de la calidad de vida. Es bien conocido que diferentes aspectos relacionados con la calidad de vida facilitan el desarrollo del lupus en individuos predispuestos. Desde hace varios años se sabe que factores tales como la exposición a los rayos ultravioleta se relacionan con el desarrollo de lupus; sin embargo, debido a factores inherentes a la globalización, a los cambios en los hábitos, a un mayor conocimiento de las vías de señalización celular, así como a una mayor comprensión de la metabolómica, la proteómica y la genómica, ha sido posible entender mejor la relación entre las células y su medio ambiente. En el presente estudio reunimos, a través de una revisión narrativa, la evidencia actual sobre diferentes factores de riesgo y el desarrollo del lupus, incluyendo aspectos típicos de la población colombiana.

Assuntos

RESUMO

The process of freezing cells or tissues and depositing them in liquid nitrogen at -196 °C is called cryopreservation. Sub-zero temperature is not a physiological condition for cells and water ice crystals represent the main problem since they induce cell death, principally in large cells like oocytes, which have a meiotic spindle that degenerates during this process. Significantly, cryopreservation represents an option for fertility preservation in patients who develop gonadal failure for any condition and those who want to freeze their germ cells for later use. The possibility of freezing sperm, oocytes, and embryos has been available for a long time, and in 1983 the first birth with thawed oocytes was achieved. From the mid-2000s forward, the use of egg vitrification through intracytoplasmic sperm injection has improved pregnancy rates. Births using assisted reproductive technologies (ART) have some adverse conditions and events. These risks could be associated with ART procedures or related to infertility. Cryopreservation generates changes in the epigenome of gametes and embryos, given that ART occurs when the epigenome is most vulnerable. Furthermore, cryoprotective agents induce alterations in the integrity of germ cells and embryos. Notably, cryopreservation extensively affects cell viability, generates proteomic profile changes, compromises crucial cellular functions, and alters sperm motility. This technique has been widely employed since the 1980s and there is a lack of knowledge about molecular changes. The emerging view is that molecular changes are associated with cryopreservation, affecting metabolism, cytoarchitecture, calcium homeostasis, epigenetic state, and cell survival, which compromise the fertilization in ART.

Assuntos

RESUMO

Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.

RESUMO

The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5-8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual's sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging.

Assuntos

RESUMO

Herbal formulas during pregnancy have been used in developing countries. Despite that, the potential effects on the mother and offspring and whether those supplements elicit epigenetic modifications is still unknown. Therefore, our objectives were to determine the effects of supplemental herbal choline source (BCho) on the percentage of 5-hmC in whole blood from gestating ewes and their offspring, as well as determining the milk quality and growth of the offspring. Thirty-five gestating Rambouillet ewes were randomly assigned to five treatments: T1, supplementation of 4 g per day (gd-1) of BCho during the first third of gestation; T2, supplementation of 4 gd-1 of BCho during the second third of gestation; T3, supplementation of 4 gd-1 of BCho during the last third of gestation; T4, supplementation of 4 gd-1 of BCho throughout gestation; and T5, no BCho supplementation (control). For the 5-hmC DNA analysis, whole blood from ewes was sampled before pregnancy and at each third of gestation (50 days). Whole blood from lambs was sampled five weeks after birth. The evaluation of the nutritional programming effects was conducted through the percentages of 5-hmC in the lambs. Compared with other treatments, the whole blood from ewes supplemented during T1 and T4 had the greatest 5-hmC percentages (p < 0.05). However, only ewes fed BCho throughout gestation (T4) maintained the greatest percentages of 5-hmC (p < 0.05). The lamb growth performance indicated that the BCho maternal supplementation did not affect the nutritional programming. However, the lambs born from ewes supplemented during T2 had the greatest 5-hmC percentages (p < 0.05). Our data suggest that ewes supplemented during T4 with BCho increase and maintain the percentages of 5-hmC in whole blood, and the offspring born from ewes supplemented with BCho during T2 maintained the greatest percentages of 5-hmC 35 d after they were born.

RESUMO

Maternal obesity has been shown to impact the offspring health during childhood and adult life. This study aimed to evaluate whether maternal obesity combined with postnatal exposure to an obesogenic diet could induce metabolic alterations in offspring. Female CD1 mice were fed a control diet (CD, 11.1% of energy from fat) or with a high-fat diet (HFD, 44.3% of energy from fat) for 3 months. After weaning, pups born from control and obese mothers were fed with CD or HFD for 3 months. Both mothers and offspring were weighted weekly and several blood metabolic parameters levels were evaluated. Here, we present evidence that the offspring from mothers exposed to a HFD showed increased acetylation levels of histone 3 on lysine 9 (H3K9) in the liver at postnatal Day 1, whereas the levels of acetylation of H4K16, dimethylation of H3K27, and trimethylation of H3K9 showed no change. We also observed a higher perinatal weight and increased blood cholesterol levels when compared to the offspring on postnatal Day 1 born from CD-fed mothers. When mice born from obese mothers were fed with HFD, we observed that they gained more weight, presented higher blood cholesterol levels, and abdominal adipose tissue than mice born to the same mothers but fed with CD. Collectively, our results point toward maternal obesity and HFD consumption as a risk factor for epigenetic changes in the liver of the offspring, higher perinatal weight, increased weight gain, and altered blood cholesterol levels.

Assuntos

RESUMO

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.

Assuntos

RESUMO

An increasing interest has been developed in the past 15 years in the relationship between trace elements and cell functioning. In the present work the possibility of transgenerational effects of Te was investigated in rats. F1 generation exposed to K2TeO3 (1.55nM) from day 1 of pregnancy until litters were 30 day old, these animals with no other treatment than tap water and food were let to reach 60-70 day old. At this age, female rats were mated with normal untreated male rats. The F2 generation also without any Te treatment was allowed to grow until 30 days of age. At this age, behavioral tests measuring exploration induced by novelty, lateralized exploration, social interaction and survival behavior were applied. Results showed that head-dipping, rearing, lateralized exploration, social interaction, and survival behaviors, affected by Te treatment in F1 generation, also were modified in the same manner in F2 generation. These data show that Te effects on coping behavior in rats are preserved epigenetically in the next generation.

Assuntos

RESUMO

MAIN CONCLUSION: Heterografting induced intraclonal epigenetic variations were detected among rubber plants. Interaction between genetically divergent root stock and scion tissues might have triggered these epigenetic changes which may eventually lead to intraclonal variability in rubber. DNA methylation in response to stress may be associated with the alteration in gene transcription leading to morphological changes in plants. Rubber tree is commercially propagated by bud grafting where the scion of a high yielding variety is grafted on to a genetically divergent root stock. Still, significant levels of intraclonal variations exist among them. Epigenetic changes associated with heterografting may be partly responsible for this conundrum. In the present study, an attempt was made to identify the impact of divergent root stock on the epigenome of scion in grafted rubber plants. Heterografts were developed by grafting eye buds from a single polyembryony derived seedling on to genetically divergent root stocks of unknown parentage. The plants were uniformly maintained and their DNA was subjected to MSAP analysis. Polymorphic DNA methylation bands corresponding to CG as well as the plant-specific CHG types of methylation were observed. Cloning of selected polymorphic regions and bisulfite sequencing confirmed the presence of methylation in the promoter and coding region of important genes including an LRR receptor kinase gene. Since divergent root stock is the major factor differentiating the grafted plants, the changes in DNA methylation patterns might have been triggered by the interaction between the two genetically different tissues of stock and scion. The study assumes importance in Hevea, because accumulation and maintenance of epigenetic changes in functional genes and promoters during subsequent cycles of vegetative propagation may contribute towards intraclonal variability eventually leading to altered phenotypes.

Assuntos