scholarly journals Elevated IL-6 in Pre-Eclampsia Increases Neurite Growth and Mitochondrial Respiration in an in vitro Model of Neuronal Development

2021 ◽  
Author(s):  
Aaron Barron ◽  
Samprikta Manna ◽  
Colm McElwain ◽  
Andrea Musumeci ◽  
Fergus McCarthy ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Neuronal Development ◽  
Neonatal Morbidity ◽  
Neurite Growth ◽  
Maternal Serum ◽  
Hypertensive Disorder ◽  
Uncomplicated Pregnancy ◽  
Increased Risk ◽  
Control Serum

Abstract Pre-eclampsia (PE) is a common and serious hypertensive disorder of pregnancy, which affects 3-5% of first-time pregnancies and is a leading cause of maternal and neonatal morbidity and mortality. Prenatal exposure to PE is associated with an increased risk of neurodevelopmental disorders in affected offspring, although the cellular and molecular basis of this are largely unknown. In this study we examined the effects of exposure to maternal serum from women with PE or a healthy uncomplicated pregnancy on the survival, neurite growth and mitochondrial function of SH-SY5Y cells. We report that cells exposed to PE serum exhibited increased neurite growth and mitochondrial respiration, two important neurodevelopmental parameters, compared to those treated with control serum. Levels of the pleiotropic cytokine IL-6 were significantly elevated in the PE sera, and cells exposed to PE serum displayed increased phospho-STAT3 levels which is a key intracellular mediator of IL-6 signalling. Finally, we show that treating these cells with IL-6 alone is sufficient to induce a similar neurite growth and respiratory phenotype to PE serum-exposed cells. This suggests that elevated IL-6 seen in maternal serum in PE may be responsible at least in part for its inducing increased neurite growth and mitochondrial respiration in SH-SY5Y cells. Overall, this study demonstrates that there are circulating factors in the serum of women with pre-eclampsia that affect neuronal development and oxygen consumption differently to that of a healthy uncomplicated pregnancy, and that immune dysregulation via elevated IL-6 may be important in mediating these effects.

scholarly journals Inositol Deficiency Induces Autophagy Impairing via PI3K/Akt/mTOR/p70S6K Signaling (P11-032-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jianhua Wang ◽  
Jin Guo
Keyword(s):  
Signaling Pathway ◽  
Basic Research ◽  
Treated Group ◽  
Maternal Serum ◽  
Additional Treatment ◽  
Pi3 Kinase ◽  
Dependent Manner ◽  
Pi3k Activity ◽  
Increased Risk

Abstract Objectives Our previous case-control study found that maternal MI deficiency was associated with an increased risk of NTDs. Bioinformatics analysis showed that PI3K/Akt/mTOR/p70S6K signaling pathway might be one of the important regulatory mechanisms of inositol deficiency-induced NTDs. So, we intended to explore the possible mechanisms of PI3K/Akt/mTOR/p70S6K signaling in inositol deficiency-induced neural tube defects (NTDs) in this study. Methods The activity of the PI3-kinase in MI deficiency NE-4C cells was detected by the PI3-kinase ELISA kit. Using the method of western blot, we analyzed the activity of the PI3K/Akt/mTore/p70S6K signaling pathway and the level of LC3B. And the LC3B levels were also detected by electron microscopy. Results The result showed that PI3K activity was significantly higher in the Li2CO3-treated group than in the control cells (P < 0.05), and the increased kinase activity was abolished by additional treatment with MI (P < 0.05). We found that PI3K activity decreased dramatically with the increasing MI concentration in a dose-dependent manner when the inositol concentration was below 5 mg/L in vitro enzymology experiment. The result showed that the PI3K/Akt/mTOR/p70S6K signaling pathway significant activated in MI deficient NE-4C cells compare with the controls. We found that the autophagy was significantly impaired by Li2CO3 treatment in NE-4C cells, and the effects were abrogated by combining Li2CO3 with MI or signaling inhibitor (Ly294002 and Rapamycin). Which suggested that MI deficiency induced autophagy impairment through the Akt/mTOR/p70S6K signaling. We next validate the above result in our previous established MI deficiency mouse model and found PI3K activity was significantly elevated in heart, neural and placenta tissues 8 hours after Li2CO3 injection. The maternal serum MI levels correlated with the PI3K activity in the mouse embryonic neural tissue (R = –0.817, P < 0.05). And the activity of Akt/mTOR/p70S6K signaling was over activated accompanied by the reduced level of LC3B. Conclusions These results showed that inositol deficiency activated PI3K/Akt/mTOR/p70S6K signaling, thus causing impaired autophagy. Funding Sources This study was supported by The National Key Basic Research Program(2018YFC1002500), National Nature Science Foundation of China (81571443 to JW, 81801451 to JG).

scholarly journals Contribution of angiotensinogen M235T and T174M gene variants and haplotypes to preeclampsia and its severity in (North African) Tunisians

2018 ◽  
Vol 19 (1) ◽  
pp. 147032031775392 ◽  
Author(s):  
Hedia Zitouni ◽  
Marwa Ben Ali Gannoum ◽  
Nozha Raguema ◽  
Wided Maleh ◽  
Ines Zouari ◽  
...  
Keyword(s):  
Haplotype Analysis ◽  
Neonatal Morbidity ◽  
Minor Allele ◽  
Hypertensive Disorder ◽  
Gene Variants ◽  
North African ◽  
Increased Risk ◽  
Polymerase Chain ◽  
Agt Gene ◽  
Control Study

Background: Preeclampsia (PE) is a pregnancy-associated hypertensive disorder and a leading cause of maternal and neonatal morbidity and mortality. While its pathogenesis remains ill defined, several candidate genes for PE have been identified, but results remain inconclusive. We investigated the association of the angiotensinogen ( AGT) gene variants M235T and T174M with PE, and we analyzed the contribution of both variants to the severity of PE. Methods: This case-control study enrolled 550 Tunisian pregnant women: 272 with PE, of whom 147 presented with mild, and 125 with severe PE, along with 278 unrelated age- and ethnically matched control women. AGT genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Significantly higher M235T minor allele frequency (MAF) was associated with increased risk of PE ( p < 0.001). Decreased frequency of heterozygous T174M genotype carriers were found in control women ( p = 0.015), suggesting a protective effect of this genotype (odds ratio (95% confidence interval) = 0.51 (0.29–0.89)). Two-locus haplotype analysis demonstrated MM and TT haplotypes to be negatively and positively associated with PE, respectively. MAF of M253T, but not T174M, was higher in the severe PE group, and carrying M235T or T174M minor allele was associated with increased body mass index ( p < 0.001) among unselected PE women. Conclusions: AGT M235T and T174M variants contribute to an increased risk of developing PE, and for M235T to PE severity.

Management and outcome of high-order multiple pregnancy

1996 ◽  
Vol 8 (3) ◽  
pp. 133-142
Author(s):  
Shlomo Lipitz ◽  
Dan Grisaru ◽  
Zeev Rotstein ◽  
Reuwen Achiron
Keyword(s):  
Multiple Pregnancy ◽  
Neonatal Morbidity ◽  
High Order ◽  
Multiple Pregnancies ◽  
Maternal Complications ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
High Prevalence ◽  
Need To Evaluate

The incidence of pregnancies with three or more fetuses has markedly increased over the past two decades. The change has been attributed to the introduction and widespread use of new techniques for ovulation induction and placement of multiple embryos during in vitro fertilization (IVF). These techniques have been a matter of concern, since triplet and higher multiple pregnancies have long been associated with an increased risk of maternal complications, and a high prevalence of perinatal and neonatal morbidity and mortality. Furthermore, the developing experience with multifetal pregnancy reduction offers a new option for the management of these pregnancies. There is therefore a need to evaluate the management and outcome of high-order multiple pregnancies.

scholarly journals Cerebroplacental ratio for prediction of adverse intrapartum and neonatal outcomes in a term uncomplicated pregnancy

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Mariam Lotfy Mohamed ◽  
Salwa Adel Mohamed ◽  
Amal Mohamed Elshahat
Keyword(s):  
Neonatal Morbidity ◽  
Neonatal Outcomes ◽  
Morbidity And Mortality ◽  
Perinatal Morbidity ◽  
Uncomplicated Pregnancy ◽  
Cerebroplacental Ratio ◽  
Flow Disturbances ◽  
Increased Risk ◽  
Nicu Admission ◽  
Fetal Compromise

Abstract Background Fetal hypoxia is one of the major causes of high perinatal morbidity and mortality rates. Doppler ultrasound tests such as cerebroplacental ratio (CPR) evaluation are commonly used to assess blood flow disturbances in placento-umbilical and feto-cerebral circulations. A low cerebroplacental ratio has been shown to be associated with an increased risk of stillbirth regardless of the gestation or fetal weight. We conducted this study to assess the fetal cerebroplacental ratio in prediction of adverse intrapartum and neonatal outcomes in a term, uncomplicated pregnancy to reduce fetal and neonatal morbidity and mortality. Results It was found that neonates with CPR ≤1.1 had significantly higher frequencies of cesarean delivery (CS) for intrapartum fetal compromise compared to those with CPR >1.1 (p=0.043). Neonates with CPR ≤1.1 had significantly lower Apgar score at 1 min and 5 min than those with CPR >1.1 (p=0.004) and (p=0.003), respectively. Neonates with CPR ≤1.1 had significantly higher rates of NICU admission than those with CPR <1.1 (p=0.004). Conclusion The cerebroplacental ratio shows the highest sensitivity in the prediction of fetal heart rate abnormalities and adverse neonatal outcome in uncomplicated pregnancies at term. The cerebroplacental ratio index is useful in clinical practice in antenatal monitoring of these women in order to select those at high risk of intra- and postpartum complications.

scholarly journals Effects of ethanol-and choline-treated astrocytes on hippocampal neuron neurite outgrowth in vitro

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110189
Author(s):  
Calla M Goeke ◽  
Joel G Hashimoto ◽  
Marina Guizzetti ◽  
Annabella Vitalone
Keyword(s):  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Neuronal Development ◽  
Fetal Alcohol Spectrum Disorders ◽  
Culture Media ◽  
Neurite Growth ◽  
Alcohol Exposure ◽  
Inhibitory Effect ◽  
Human Infants

Exposure to ethanol in utero can result in Fetal Alcohol Spectrum Disorders, which may cause long-lasting cognitive and behavioral abnormalities. Preclinical studies indicate that choline ameliorates the behavioral effects of developmental alcohol exposure in rodents, and clinical studies on the effectiveness of choline, administered early in pregnancy, showed that the adverse effects of heavy prenatal alcohol exposure on postnatal growth, and cognition in human infants were mitigated. However, little is known on the mechanisms behind the effects of choline. We have previously reported that astrocyte pre-treatment with 75 mM ethanol, in vitro, reduces neurite outgrowth in hippocampal neurons co-cultured with the pre-treated astrocytes. Our in vitro system allows us to study the effects of chemicals on astrocyte functions, able to modulate neuronal development. The main objective was to test the hypothesis that choline can ameliorate the astrocyte-mediated effects of ethanol on neurite growth. In this study, we exposed primary rat cortical astrocytes to ethanol, choline, ethanol plus choline, or control conditions for 24 h. Culture media was then removed, replaced with fresh media containing no ethanol or choline treatments and primary rat hippocampal neurons were plated on top of the astrocyte monolayer and cultured for 16 h. Neurons were then stained for β-III Tubulin and neurite outgrowth was measured. Astrocyte exposure to ethanol (25, 50, and 75 mM) decreases neurite outgrowth in co-cultured hippocampal pyramidal neurons, while astrocyte treatment with choline had no effect. Astrocyte treatment with ethanol and choline in combination, however, prevented the effect of ethanol, leading to levels of neurite outgrowth similar the control condition. Choline prevents the inhibitory effect of ethanol-treated astrocytes on neurite outgrowth while not altering normal neuronal development. These results suggest a new, astrocyte-mediated mechanism by which choline ameliorates the effects of developmental alcohol exposure.

Assays for Phospholipid-Dependent Formation of Thrombin and Xa: A Potential Method for Quantifying Lupus Anticoagulant Activity

1991 ◽  
Vol 66 (04) ◽  
pp. 453-458 ◽  
Author(s):  
John T Brandt
Keyword(s):  
Specific Activity ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Clinical Importance ◽  
Potential Method ◽  
Quantitative Expression ◽  
Increased Risk ◽  
Apparent Association

SummaryLupus anticoagulants (LAs) are antibodies which interfere with phospholipid-dependent procoagulant reactions. Their clinical importance is due to their apparent association with an increased risk of thrombo-embolic disease. To date there have been few assays for quantifying the specific activity of these antibodies in vitro and this has hampered attempts to purify and characterize these antibodies. Methods for determining phospholipid-dependent generation of thrombin and factor Xa are described. Isolated IgG fractions from 7 of 9 patients with LAs were found to reproducibly inhibit enzyme generation in these assay systems, permitting quantitative expression of inhibitor activity. Different patterns of inhibitory activity, based on the relative inhibition of thrombin and factor Xa generation, were found, further substantiating the known heterogeneity of these antibodies. These systems may prove helpful in further purification and characterization of LAs.

Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

1997 ◽  
Vol 78 (04) ◽  
pp. 1173-1177 ◽  
Author(s):  
Jacek Musiał ◽  
Jakub Swadźba ◽  
Miłosz Jankowski ◽  
Marek Grzywacz ◽  
Stanisława Bazan-Socha ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Skin Incision ◽  
Anticardiolipin Antibodies ◽  
Small Blood Vessel ◽  
Anionic Phospholipids ◽  
Increased Risk ◽  
High Concentrations

SummaryAntiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and (β2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were signiF1cantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of F1brinopeptide A were detected already in the F1rst samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated signiF1cantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalciF1ed plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the F1rst time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

2019 ◽  
Vol 25 (22) ◽  
pp. 2474-2479 ◽  
Author(s):  
Alisson Diego Machado ◽  
Gustavo Rosa Gentil Andrade ◽  
Jéssica Levy ◽  
Sara Silva Ferreira ◽  
Dirce Maria Marchioni
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Coronary Artery ◽  
Coronary Artery Calcification ◽  
Serum Levels ◽  
Antioxidant Compounds ◽  
Increased Risk ◽  
Coronary Events ◽  
Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

Edible Mushrooms: Novel Medicinal Agents to Combat Metabolic Syndrome and Associated Diseases

2020 ◽  
Vol 26 (39) ◽  
pp. 4970-4981
Author(s):  
Yu-Tang Tung ◽  
Chun-Hsu Pan ◽  
Yi-Wen Chien ◽  
Hui-Yu Huang
Keyword(s):  
Metabolic Syndrome ◽  
Unsaturated Fatty Acids ◽  
Edible Mushroom ◽  
Biologically Active ◽  
Edible Mushrooms ◽  
Beta Glucan ◽  
Medicinal Mushrooms ◽  
Associated Diseases ◽  
Increased Risk

Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low-fat content and a transisomer of unsaturated fatty acids along with high fiber content, biologically active compounds such as polysaccharides or polysaccharide β-glucans, alkaloids, steroids, polyphenols and terpenoids. In vitro experiments, animal models, and even human studies have demonstrated not only fresh edible mushroom but also mushroom extract that has great therapeutic applications in human health as they possess many properties such as antiobesity, cardioprotective and anti-diabetic effect. They are considered as the unmatched source of healthy foods and drugs. The focus of this report was to provide a concise and complete review of the novel medicinal properties of fresh or dry mushroom and extracts, fruiting body or mycelium and its extracts, fiber, polysaccharides, beta-glucan, triterpenes, fucoidan, ergothioneine from edible mushrooms that may help to prevent or treat metabolic syndrome and associated diseases.

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