scholarly journals Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Serena Banu Gumusoglu ◽  
Akanksha Sri Satya Chilukuri ◽  
Benjamin Wen Qing Hing ◽  
Sabrina Marie Scroggins ◽  
Sreelekha Kundu ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Ventricular Zone ◽  
Vessel Diameter ◽  
Female Offspring ◽  
Cell Number ◽  
Differentially Expressed ◽  
Adult Males ◽  
Social Approach ◽  
Caudate Putamen ◽  
Underlying Mechanisms

AbstractPreeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring were behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically and by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior and social approach while adult females exhibited impaired procedural learning. Adult AVP-exposed males had reduced total neocortical volume. Adult AVP-exposed females had increased caudate–putamen volume, increased caudate–putamen cell number, and decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, and CA3. At postnatal day 7 (P7), AVP-exposed male and female offspring both had smaller neocortex. At P7, AVP-exposed males also had smaller caudate–putamen volume, while females had increased caudate–putamen volume relative to neocortical size. Similar to P7, E18 AVP-exposed offspring had smaller dorsal forebrain, mainly in reduced intermediate, subventricular, and ventricular zone volume, particularly in males. Decreased volume was not accounted for by cell size or cerebrovascular vessel diameter changes. E18 cortical RNAseq revealed 49 differentially-expressed genes in male AVP-exposed offspring, over-representing cytoplasmic translation processes. In females, 31 genes were differentially-expressed, over-representing collagen-related and epithelial regulation pathways. Gene expression changes in E18 AVP-exposed placenta indicated potential underlying mechanisms. Deficits in behavior and forebrain development in this AVP-based preeclampsia model were distinctly different in males and females, implicating different neurobiological bases.

scholarly journals CircFAM13B promotes the proliferation of hepatocellular carcinoma by sponging miR-212, upregulating E2F5 expression and activating the P53 pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Xie ◽  
Xiaofeng Hang ◽  
Wensheng Xu ◽  
Jing Gu ◽  
Yuanjing Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Novel Target ◽  
Underlying Mechanisms

Abstract Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.

scholarly journals Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Yuan ◽  
Shenqiang Hu ◽  
Liang Li ◽  
Chunchun Han ◽  
Hehe Liu ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Lipid Droplets ◽  
Cell Model ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Follicle Development ◽  
Microscopy Analysis ◽  
Stearoyl Coa Desaturase ◽  
Underlying Mechanisms

Abstract Background Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Results Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. Conclusions This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.

scholarly journals Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

2018 ◽  
Vol 50 (6) ◽  
pp. 2071-2085 ◽  
Author(s):  
Wentao Hu ◽  
Weiwei Pei ◽  
Lin Zhu ◽  
Jing Nie ◽  
Hailong Pei ◽  
...  
Keyword(s):  
Human Lung ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Bronchial Epithelial ◽  
Qrt Pcr ◽  
Microarray Profiling ◽  
Underlying Mechanisms ◽  
Pathway Analyses ◽  
Trans Regulation ◽  
Tgf Β1

Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.

scholarly journals Study of the antiproliferative potential of seed extracts from Northeastern Brazilian plants

2011 ◽  
Vol 83 (3) ◽  
pp. 1045-1058 ◽  
Author(s):  
Paulo Michel P. Ferreira ◽  
Davi F. Farias ◽  
Martônio P. Viana ◽  
Terezinha M. Souza ◽  
Ilka M. Vasconcelos ◽  
...  
Keyword(s):  
Human Cancer ◽  
Ethanolic Extract ◽  
Cell Number ◽  
Northeastern Brazil ◽  
Human Cancer Cells ◽  
Ic50 Value ◽  
Underlying Mechanisms ◽  
Apoptotic Pathways ◽  
Seed Extracts

This study assessed the antiproliferative and cytotoxic potential against tumor lines of ethanolic seed extracts of 21 plant species belonging to different families from Northeastern Brazil. In addition, some underlying mechanisms involved in this cytotoxicity were also investigated. Among the 21 extracts tested, the MTT assay after 72 h of incubation demonstrated that only the ethanolic extract obtained from Myracrodruon urundeuva seeds (EEMUS), which has steroids, alkaloids and phenols, showed in vitro cytotoxic activity against human cancer cells, being 2-fold more active on leukemia HL-60 line [IC50 value of 12.5 (9.5-16.7) μg/mL] than on glioblastoma SF-295 [IC50 of 25.1 (17.3-36.3) μg/mL] and Sarcoma 180 cells [IC50 of 38.1 (33.5-43.4) μg/mL]. After 72h exposure, flow cytometric and morphological analyses of HL-60-treated cells showed that EEMUS caused decrease in cell number, volume and viability as well as internucleosomal DNA fragmentation in a dose-dependent way, suggesting that the EEMUS triggers apoptotic pathways of cell death.

scholarly journals Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging

2020 ◽  
Vol 21 (6) ◽  
pp. 1908 ◽  
Author(s):  
Hongxia Zhang ◽  
Kunlin Jin
Keyword(s):  
Target Genes ◽  
Differentially Expressed ◽  
Molecular Signaling ◽  
Slow Development ◽  
Exosomal Mirnas ◽  
Pathways Analysis ◽  
Old Rats ◽  
Underlying Mechanisms ◽  
Signaling Components ◽  
Serum Exosomes

People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation. Therefore, we used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. We identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

scholarly journals Proximal and Distal Nephron-specific Adaptation to Furosemide

2021 ◽  
Author(s):  
Aram J. Krauson ◽  
Steven Schaffert ◽  
Elisabeth M. Walczak ◽  
Jonathan M. Nizar ◽  
Gwen M. Holdgate ◽  
...  
Keyword(s):  
Cell Number ◽  
Differentially Expressed ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Distal Nephron ◽  
Transcriptional Responses ◽  
Cell Hyperplasia ◽  
Diuretic Resistance ◽  
Nephron Segments ◽  
Renal Tubular

ABSTRACTFurosemide, a widely prescribed diuretic for edema-forming states, inhibits sodium reabsorption in the thick ascending limb of the nephron. Tubular adaptation to diuretics has been observed, but the range of mechanisms along the nephron has not been fully explored. Using morphometry, we show that furosemide induces renal tubular epithelial hyperplasia selectively in distal nephron segments. By comparison, we find progressive cellular hypertrophy in proximal and distal nephron segments. We next utilize single cell RNA sequencing of vehicle- and furosemide-treated mice to define potential mechanisms of diuretic resistance. Consistent with distal tubular cell hyperplasia, we detect a net increase in DCT cell number and Birc5, an anti-apoptotic and pro-growth gene, in a subset of DCT cells, as the most prominently up-regulated gene across the nephron. We also map a gradient of cell-specific transcriptional changes congruent with enhanced distal sodium transport. Furosemide stimulates expression of the mitogen IGF-1. Thus, we developed a mouse model of inducible deletion of renal tubular IGF-1 receptor and show reduced kidney growth and proximal, but not distal, tubular hypertrophy by furosemide. Moreover, genes that promote enhanced bioavailability of IGF-1 including Igfbp1 and Igfbp5 are significantly and differentially expressed in proximal tubular segments and correspond to IGF-1R-dependent hypertrophy. In contrast, downstream PI3-kinase signaling genes including Pdk1, Akt1, Foxo3, FKBP4, Eif2BP4, and Spp1 are significantly and differentially expressed in distal nephron segments and correspond to IGF-1R-independent hypertrophy. These findings highlight novel mechanisms of tubular remodeling and diuretic resistance, provide a repository of transcriptional responses to a common drug, and expand the implications of long-term loop diuretic use for human disease.

scholarly journals Alterations of Subcortical Brain Structures in Paradoxical and Psychophysiological Insomnia Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Farnoosh Emamian ◽  
Mostafa Mahdipour ◽  
Khadijeh Noori ◽  
Masoumeh Rostampour ◽  
S. Bentolhoda Mousavi ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Brain Structures ◽  
Subcortical Structures ◽  
Caudate Putamen ◽  
Subcortical Brain ◽  
Insomnia Disorder ◽  
Sleep Parameters ◽  
Subcortical Brain Structures ◽  
Psychophysiological Insomnia ◽  
Underlying Mechanisms

Insomnia disorder (ID) is a common illness associated with mood and cognitive impairments. Subtyping ID is an ongoing debate in sleep medicine, but the underlying mechanisms of each subtype is poorly understood. Growing evidence suggests that subcortical brain structures play the key roles in pathophysiology of ID and its subtypes. Here, we aimed to investigate structural alteration of subcortical regions in patients with two common ID subtypes i.e., paradoxical and psychophysiological insomnia. Fifty-five patients and 49 healthy controls were recruited for this study and T1-weighted images and subjective and objective sleep parameters (i.e., Pittsburgh Sleep Quality Index and polysomnography) were collected from participants. Subcortical structures including the hippocampus, amygdala, caudate, putamen, globus pallidus, nucleus accumbens, and thalamus were automatically segmented in FSL. Volume and shape (using surface vertices) of each structure were compared between the groups, controlled for covariates, and corrected for multiple comparisons. In addition, correlations of sleep parameters and surface vertices or volumes were calculated. The caudate's volume was smaller in patients than controls. Compared with controls, we found regional shrinkage in the caudate, nucleus accumbens, posterior putamen, hippocampus, thalamus, and amygdala in paradoxical insomnia and shrinkage in the amygdala, caudate, hippocampus, and putamen in psychophysiological insomnia. Interestingly, comparing two patients groups, shape alteration in the caudate, putamen, and nucleus accumbens in paradoxical insomnia and shrinkage in the thalamus, amygdala, and hippocampus in psychophysiological insomnia were observed. Both subjective and objective sleep parameters were associated with these regional shape alterations in patients. Our results support the differential role of subcortical brain structures in pathophysiology of paradoxical and psychophysiological insomnia.

Genome reprogramming inSaccharomyces cerevisiaeupon nonylphenol exposure

2017 ◽  
Vol 49 (10) ◽  
pp. 549-566 ◽  
Author(s):  
Ceyhun Bereketoglu ◽  
Kazim Yalcin Arga ◽  
Serpil Eraslan ◽  
Bulent Mertoglu
Keyword(s):  
Inhibitory Concentration ◽  
Cell Number ◽  
Differentially Expressed ◽  
Ribosomal Biogenesis ◽  
Cell Wall Biogenesis ◽  
Genome Wide ◽  
Transport Response ◽  
Shock Proteins ◽  
Ubiquitin Conjugating Enzymes ◽  
Upregulated Genes

Bioaccumulative environmental estrogen, nonylphenol (NP; 4-nonylphenol), is widely used as a nonionic surfactant and can affect human health. Since genomes of Saccharomyces cerevisiae and higher eukaryotes share many structural and functional similarities, we investigated subcellular effects of NP on S. cerevisiae BY4742 cells by analyzing genome-wide transcriptional profiles. We examined effects of low (1 mg/l; <15% cell number reduction) and high (5 mg/l; >65% cell number reduction) inhibitory concentration exposures for 120 or 180 min. After 120 and 180 min of 1 mg/l NP exposure, 187 (63 downregulated, 124 upregulated) and 103 genes (56 downregulated, 47 upregulated), respectively, were differentially expressed. Similarly, 678 (168 repressed, 510 induced) and 688 genes (215 repressed, 473 induced) were differentially expressed in cells exposed to 5 mg/l NP for 120 and 180 min, respectively. Only 15 downregulated and 63 upregulated genes were common between low and high NP inhibitory concentration exposure for 120 min, whereas 16 downregulated and 31 upregulated genes were common after the 180-min exposure. Several processes/pathways were prominently affected by either low or high inhibitory concentration exposure, while certain processes were affected by both inhibitory concentrations, including ion transport, response to chemicals, transmembrane transport, cellular amino acids, and carbohydrate metabolism. While minimal expression changes were observed with low inhibitory concentration exposure, 5 mg/l NP treatment induced substantial expression changes in genes involved in oxidative phosphorylation, cell wall biogenesis, ribosomal biogenesis, and RNA processing, and encoding heat shock proteins and ubiquitin-conjugating enzymes. Collectively, these results provide considerable information on effects of NP at the molecular level.

scholarly journals Estrogen Receptor-β Mediates Dihydrotestosterone-Induced Stimulation of the Arginine Vasopressin Promoter in Neuronal Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3371-3382 ◽  
Author(s):  
Toni R. Pak ◽  
Wilson C. J. Chung ◽  
Laura R. Hinds ◽  
Robert J. Handa
Keyword(s):  
Androgen Receptor ◽  
Cell Line ◽  
Arginine Vasopressin ◽  
Promoter Activity ◽  
Neuronal Cell ◽  
Luciferase Reporter ◽  
Adult Males ◽  
Primary Metabolite ◽  
Neuronal Cell Line ◽  
The Brain

Arginine vasopressin (AVP) is a neuropeptide involved in the regulation of fluid balance, stress, circadian rhythms, and social behaviors. In the brain, AVP is tightly regulated by gonadal steroid hormones in discrete regions with gonadectomy abolishing and testosterone replacement restoring normal AVP expression in adult males. Previous studies demonstrated that 17β-estradiol, a primary metabolite of testosterone, is responsible for restoring most of the AVP expression in the brain after castration. However, 5α-dihydrotestosterone (DHT) has also been shown to play a role in the regulation of AVP expression, thus implicating the involvement of both androgen and estrogen receptors (ER). Furthermore, DHT, through its conversion to 5α-androstane-3β,17β-diol, has been shown to modulate estrogen response element-mediated promoter activity through an ER pathway. The present study addressed two central hypotheses: 1) that androgens directly modulate AVP promoter activity and 2) the effect is mediated by an estrogen or androgen receptor pathway. To that end, we overexpressed androgen receptor, ERβ, and ERβ splice variants in a neuronal cell line and measured AVP promoter activity using a firefly luciferase reporter assay. Our results demonstrate that DHT and its metabolite 5α-androstane-3β,17β-diol stimulate AVP promoter activity through ERβ in a neuronal cell line.

scholarly journals Large mothers, but not large fathers, influence offspring number in a caridean shrimp

2018 ◽  
Vol 96 (10) ◽  
pp. 1106-1113 ◽  
Author(s):  
D.E. Sganga ◽  
C. Tropea ◽  
M. Valdora ◽  
M.F. Statti ◽  
L.S. López Greco
Keyword(s):  
Reproductive Output ◽  
Growth Period ◽  
Female Offspring ◽  
Growth Increment ◽  
Adult Males ◽  
Lipid Concentration ◽  
Offspring Quality ◽  
Offspring Number ◽  
Males And Females ◽  
The Relationship

The relationship between parental mass and female reproductive output, as well as offspring quality, was studied in the red cherry shrimp (Neocaridina davidi (Bouvier, 1904)) under controlled laboratory conditions. Adult males and females of the same age were paired combining different shrimp masses. The number of hatched juveniles from large females was higher than that from small ones, but no influence of paternal mass was detected on this variable. Both the mass of newly hatched juveniles and their growth increment during a 60-day period were similar for all parental masses. Shrimps reached sexual maturity at the end of the growth period in all treatments, and their biochemical reserves (glycogen, lipid, and protein concentrations) were not associated with maternal and paternal masses. However, lipid concentration was higher in female offspring than in male offspring. The present results show that, unlike maternal mass, paternal mass had no effect on female reproductive output and offspring quality, suggesting that the contribution of males to offspring development was adequate regardless of male size.

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