scholarly journals Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1608 ◽  
Author(s):  
Yu Gao ◽  
Chiranjib Dasgupta ◽  
Lei Huang ◽  
Rui Song ◽  
Ziwei Zhang ◽  
...  
Keyword(s):  
Heart Development ◽  
Tca Cycle ◽  
Dependent Manner ◽  
Omics Data ◽  
Long Term Effects ◽  
Mitochondrial Translation ◽  
Pregnant Rats ◽  
Antenatal Hypoxia ◽  
Developing Heart ◽  
The Impact

Antenatal hypoxia caused epigenetic reprogramming of methylome and transcriptome in the developing heart and increased the risk of heart disease later in life. Herein, we investigated the impact of gestational hypoxia in proteome and metabolome in the hearts of fetus and adult offspring. Pregnant rats were treated with normoxia or hypoxia (10.5% O2) from day 15 to 21 of gestation. Hearts were isolated from near-term fetuses and 5 month-old offspring, and proteomics and metabolomics profiling was determined. The data demonstrated that antenatal hypoxia altered proteomics and metabolomics profiling in the heart, impacting energy metabolism, lipid metabolism, oxidative stress, and inflammation-related pathways in a developmental and sex dependent manner. Of importance, integrating multi-omics data of transcriptomics, proteomics, and metabolomics profiling revealed reprogramming of the mitochondrion, especially in two clusters: (a) the cluster associated with “mitochondrial translation”/“aminoacyl t-RNA biosynthesis”/“one-carbon pool of folate”/“DNA methylation”; and (b) the cluster with “mitochondrion”/“TCA cycle and respiratory electron transfer”/“acyl-CoA dehydrogenase”/“oxidative phosphorylation”/“complex I”/“troponin myosin cardiac complex”. Our study provides a powerful means of multi-omics data integration and reveals new insights into phenotypic reprogramming of the mitochondrion in the developing heart by fetal hypoxia, contributing to an increase in the heart vulnerability to disease later in life.

scholarly journals Gestational Monosodium Glutamate Exposure Effects on Anogenital Distance of Male Rat Pups

2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Amelya Permata Sari ◽  
Cimi Ilmiawati ◽  
Mohamad Reza
Keyword(s):  
Monosodium Glutamate ◽  
Maternal Serum ◽  
Male Rat ◽  
High Dose ◽  
Dependent Manner ◽  
Pregnant Rats ◽  
Anogenital Distance ◽  
Estrogen Level ◽  
Rat Pups ◽  
The Impact

High-dose Monosodium Glutamate (MSG) expo sure increases the estrogen level in pregnant rats. However, there are limited data available on whether the MSG-related maternal hormonal effects can affect male litters' genitalia phenotype. This study aimed to analyze the impact of MSG on estrogen level in pregnant rats and anogenital distance in male pups. Experiment for this study was performed at the animal facility of Biomedical Laboratory at the Faculty of Medicine, Universitas Andalas, from April 2019 to February 2020. Pregnant Wistar rats were given MSG orally at 2 and 4 mg/g body weight (BW) for 20 days. On day 21, pregnant rats were sacrificed and blood was drawn intracardially. Estradiol serum level was measured by ELISA. Male pups were counted, and the anogenital distance (AGD) was measured. Maternal serum estradiol levels were statistically analyzed by One-Way ANOVA and the AGD of male litters were analyzed by the Kruskal-Wallis test. Results showed that perinatal MSG exposure increased the estradiol level (26.3±4.5 pg/ml; 37.5±6.7 pg/ml; 62.1±8.2 pg/ml in control, 2 mg/g BW, and 4 mg/g BW group, respectively [mean±SD; p=<0.001]) and decreased the AGD (4 mm; 3 mm; 1.5 mm in control, 2 mg/g BW, and 4 mg/gBW group, respectively [median; p=<0.01]) in a dose-dependent manner. Thus, MSG exposure during pregnancy is a risk factor for male rat feminization.

scholarly journals Promoter methylation of Egr-1 site contributes to fetal hypoxia-mediated PKCε gene repression in the developing heart

2013 ◽  
Vol 304 (9) ◽  
pp. R683-R689 ◽  
Author(s):  
Man Chen ◽  
Fuxia Xiong ◽  
Lubo Zhang
Keyword(s):  
Binding Site ◽  
Expression Patterns ◽  
Estrogen Receptor Α ◽  
Gene Repression ◽  
Early Developmental Stage ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Fetal Hypoxia ◽  
Pregnant Rats ◽  
Developing Heart

Fetal hypoxia causes protein kinase Cε (PKCε) gene repression in the heart resulting in heightened ischemic injury in male offspring in a sex-dependent manner. The present study tested the hypothesis that heightened methylation of the early growth response factor-1 (Egr-1) binding site at PKCε gene promoter contributes to sex dimorphism of hypoxia-induced programming of PKCε gene repression in the developing heart. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from day 15 to 21 of gestation) groups. Hypoxia selectively decreased PKCε mRNA and protein abundance in the heart of male, but not female, near-term (21 days) fetuses. Methylation of the CpG site at the Egr-1 binding site of PKCε promoter was significantly increased in the male hearts by hypoxia, resulting in decreased Egr-1 binding affinity and reduced Egr-1 binding to the PKCε promoter. Nuclear Egr-1 levels were not affected by hypoxia. There was significantly higher abundance of estrogen receptor α (ERα) and β (ERβ) isoforms in female than in male fetal hearts, which were not significantly altered by hypoxia. Both ERα and ERβ bind to the Egr-1 binding site with significant greater levels in the female fetal hearts. The increased methylation with reduced Egr-1 binding and PKCε gene repression persisted in 3-mo-old adult male hearts in a sex-dependent manner. The results indicate a key role for heightened methylation of the Egr-1 binding site in hypoxia-mediated programming of PKCε gene repression in the developing heart and suggest a novel protective mechanism of ER by binding to the Egr-1 binding site in epigenetic regulation of PKCε gene expression patterns in the early developmental stage.

Unravelling the impact of intrauterine growth restriction on heart development: insights into mitochondria and sexual dimorphism from a non-hominoid primate

2021 ◽  
Vol 135 (14) ◽  
pp. 1767-1772
Author(s):  
George W. Booz ◽  
Gaelle P. Massoud ◽  
Raffaele Altara ◽  
Fouad A. Zouein
Keyword(s):  
Heart Development ◽  
In Utero ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Primate Model ◽  
Mitochondrial Ros ◽  
Mitochondrial Functions ◽  
Mitochondrial Transcripts ◽  
The Impact

Abstract Fetal exposure to an unfavorable intrauterine environment programs an individual to have a greater susceptibility later in life to non-communicable diseases, such as coronary heart disease, but the molecular processes are poorly understood. An article in Clinical Science recently reported novel details on the effects of maternal nutrient reduction (MNR) on fetal heart development using a primate model that is about 94% genetically similar to humans and is also mostly monotocous. MNR adversely impacted fetal left ventricular (LV) mitochondria in a sex-dependent fashion with a greater effect on male fetuses, although mitochondrial transcripts increased more so in females. Increased expression for several respiratory chain and adenosine triphosphate (ATP) synthase proteins were observed. However, fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, likely contributing to a 73% decreased LV ATP content and increased LV lipid peroxidation. Moreover, MNR fetal LV mitochondria showed sparse and disarranged cristae. This study indicates that mitochondria are targets of the remodeling and imprinting processes in a sex-dependent manner. Mitochondrial ROS production and inadequate energy production add another layer of complexity. Altogether these observations raise the possibility that dysfunctional mitochondria in the fetus may contribute in turn to epigenetic memory of in utero stress in the adult. The role of mitoepigenetics and involvement of mitochondrial and genomic non-coding RNAs in mitochondrial functions and nuclei–mitochondria crosstalk with in utero stress awaits further investigation.

SUMBER-SUMBER RESILIENSI PADA REMAJA AKHIR YANG MENGALAMI KEKERASAN DARI ORANGTUA PADA MASA KANAK-KANAK

Psibernetika ◽  
2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Devina Calista ◽  
Garvin Garvin
Keyword(s):  
Late Adolescents ◽  
Long Term Effects ◽  
Short Term ◽  
Parental Affection ◽  
Resilience Factors ◽  
Childhood Violence ◽  
Past Experiences ◽  
The Impact ◽  
Depth Interviews

<p><em>Child abuse by parents is common in households. The impact of violence on children will bring short-term effects and long-term effects that can be attributed to their various emotional, behavioral and social problems in the future; especially in late adolescence that will enter adulthood. Resilience factors increase the likelihood that adolescents who are victims of childhood violence recover from their past experiences</em><em>,</em><em> become more powerful individuals and have a better life. The purpose of this study was to determine the source of resilience in late adolescents who experienced violence from parents in their childhood. This research uses qualitative research methods with in-depth interviews as a method of data collection. The result shows that the three research participants have the aspects of "I Have", "I Am", and "I Can"; a participant has "I Can" aspects as a source of resilience, and one other subject has no source of resilience. The study concluded that parental affection and acceptance of the past experience have role to the three sources of resilience (I Have, I Am, and I Can)</em></p><p><em> </em></p><p><strong><em>Keyword : </em></strong><em>Resilience, adolescence, violence, parents</em></p>

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

The Quantification of Structural Reforms in OECD Countries

2018 ◽  
Author(s):  
Balázs Égert ◽  
Peter Gal
Keyword(s):  
Product Market ◽  
Physical Capital ◽  
Oecd Countries ◽  
Market Regulation ◽  
Structural Reforms ◽  
Long Term Effects ◽  
Per Capita ◽  
Product Market Regulation ◽  
The Impact

This chapter describes and discusses a new supply-side framework that quantifies the impact of structural reforms on per capita income in OECD countries. It presents the overall macroeconomic impacts of reforms by aggregating over the effects on physical capital, employment, and productivity through a production function. On the basis of reforms defined as observed changes in policies, the chapter finds that product market regulation has the largest overall single policy impact five years after the reforms. But the combined impact of all labour market policies is considerably larger than that of product market regulation. The paper also shows that policy impacts can differ at different horizons. The overall long-term effects on GDP per capita of policies transiting through capital deepening can be considerably larger than the five- to ten-year impacts. By contrast, the long-term impact of policies coming only via the employment rate channel materializes at a shorter horizon.

scholarly journals Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Cohort Study: influences of complex environmental exposures on maternal and child health in Suriname

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e034702
Author(s):  
Wilco Zijlmans ◽  
Jeffrey Wickliffe ◽  
Ashna Hindori-Mohangoo ◽  
Sigrid MacDonald-Ottevanger ◽  
Paul Ouboter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Occupational Health ◽  
Pregnant Women ◽  
Fish Consumption ◽  
Depression Scale ◽  
Environmental Exposures ◽  
International Standards ◽  
Long Term Effects ◽  
The Impact ◽  
Environmental And Occupational Health

PurposeThe Caribbean Consortium for Research in Environmental and Occupational Health prospective environmental epidemiologic cohort study addresses the impact of chemical and non-chemical environmental exposures on mother/child dyads in Suriname. The study determines associations between levels of environmental elements and toxicants in pregnant women, and birth outcomes and neurodevelopment in their children.ParticipantsPregnant women (N=1143) were enrolled from December 2016 to July 2019 from three regions of Suriname: Paramaribo (N=738), Nickerie (N=204) and the tropical rainforest interior (N=201). Infants (N=992) were enrolled at birth. Follow-up will take place until children are 48 months old.Findings to dateBiospecimens and questionnaire data on physiological and psychosocial health in pregnant women have been analysed. 39.1% had hair mercury (Hg) levels exceeding values considered safe by international standards. Median hair Hg concentrations in women from Paramaribo (N=522) were 0.64 µg/g hair (IQRs 0.36–1.09; range 0.00–7.12), from Nickerie (N=176) 0.73 µg/g (IQR 0.45–1.05; range 0.00–5.79) and the interior (N=178) 3.48 µg/g (IQR 1.92–7.39; range 0.38–18.20). 96.1% of women ate fish, respective consumption of the three most consumed carnivorous species, Hoplias aimara, Serrasalmus rhombeus and Cichla ocellaris, known to have high Hg levels, was 44.4%, 19.3% and 26.3%, respectively, and was greater among the interior subcohort. 89% frequently consumed the vegetable tannia, samples of which showed presence of worldwide banned pesticides. 24.9% of pregnant women had Edinburgh Depression Scale scores indicative of probable depression.Future plansFish consumption advisories are in development, especially relevant to interior women for whom fish consumption is likely to be the primary source of Hg exposure. Effects of potentially beneficial neuroprotective factors in fish that may counter neurotoxic effects of Hg are being examined. A pesticide literacy assessment in pregnant women is in progress. Neurodevelopmental assessments and telomere length measurements of the children to evaluate long-term effects of prenatal exposures to toxicant mixtures are ongoing.

scholarly journals The psychological impact of the COVID-19 pandemic on adults with autism: a survey study across three countries

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danna Oomen ◽  
Annabel D. Nijhof ◽  
Jan R. Wiersema
Keyword(s):  
Mental Health ◽  
Social Life ◽  
Social Stress ◽  
Mental Health Problems ◽  
Survey Study ◽  
Specific Information ◽  
Long Term Effects ◽  
Adults With Autism ◽  
Psychological Burden ◽  
The Impact

Abstract Background Previous studies have reported a negative psychological and mental health impact of the COVID-19 pandemic. This impact is likely to be stronger for people with autism as they are at heightened risk of mental health problems and because the pandemic directly affects social functioning and everyday routines. We therefore examined COVID-19 pandemic-related changes in mental health, the impact of the pandemic on their social life and routines, satisfaction with pandemic-related information and tips, and participants’ wishes for guidance. Methods We used a mixed-method approach, collecting quantitative and qualitative survey data from adults with and without autism across three European countries: Belgium, the Netherlands, and the UK (N = 1044). Results We found an increase in depression and anxiety symptoms in response to the pandemic for both the non-autism and the autism group, which was greater for adults with autism. Furthermore, adults with autism showed a greater increase in worries about their pets, work, getting medication and food, and their own safety/security. They felt more relieved from social stress, yet experienced the loss of social contact as difficult. Adults with autism also felt more stressed about the loss of routines. Pleasant changes noted by adults with autism were the increase in solidarity and reduced sensory and social overload. Adults with autism frequently reported problems with cancellation of guidance due to the pandemic and expressed their wish for (more) autism-specific information and advice. Limitations Our sample is likely to reflect some degree of selection bias, and longitudinal studies are needed to determine long-term effects. Conclusions Results highlight the psychological burden of the pandemic on adults with autism and shed light on how to support them during this COVID-19 pandemic, which is especially important now that the pandemic is likely to have a prolonged course. There is a need for accessible, affordable (continued) support from health services. Guidance may focus on the maintenance of a social network, and adjusting routines to the rapid ongoing changes. Finally, we may learn from the COVID-19 pandemic-related changes experienced as pleasant by adults with autism to build a more autism-friendly society post-pandemic.

scholarly journals Arginine Decarboxylase Is Essential for Pneumococcal Stress Responses

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 286
Author(s):  
Mary Frances Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Mirghani Mohamed ◽  
Edwin Swiatlo ◽  
...  
Keyword(s):  
Stress Responses ◽  
Critical Role ◽  
Acid Stress ◽  
Arginine Decarboxylase ◽  
Arginine Deiminase ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Opportunistic Human Pathogen ◽  
Thiol Peroxidase ◽  
The Impact

Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host–pathogen interactions. Streptococcus pneumoniae is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality worldwide. As it transits through different host niches, S. pneumoniae is exposed to and must adapt to different types of stress in the host microenvironment. We earlier reported that S. pneumoniae TIGR4, which harbors an isogenic deletion of an arginine decarboxylase (ΔspeA), an enzyme that catalyzes the synthesis of agmatine in the polyamine synthesis pathway, has a reduced capsule. Here, we report the impact of arginine decarboxylase deletion on pneumococcal stress responses. Our results show that ΔspeA is more susceptible to oxidative, nitrosative, and acid stress compared to the wild-type strain. Gene expression analysis by qRT-PCR indicates that thiol peroxidase, a scavenger of reactive oxygen species and aguA from the arginine deiminase system, could be important for peroxide stress responses in a polyamine-dependent manner. Our results also show that speA is essential for endogenous hydrogen peroxide and glutathione production in S. pneumoniae. Taken together, our findings demonstrate the critical role of arginine decarboxylase in pneumococcal stress responses that could impact adaptation and survival in the host.

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