•Hyperactivation of NLRP3 inflammasome was proposed in placentas from pregnant women with severe preeclampsia.•IL-1β, TNF-α and HMGB1may be involved in the exaggerated systemic inflammation of ...preeclampsia.•Placental inflammasome activation may be involved in the pathogenesis of preeclampsia.
Preeclampsia is a pregnancy disorder characterized by imbalance between pro- and anti-inflammatory cytokines associated with high plasma levels of uric acid and Interleukin-1 beta (IL-1β). The inflammasome is a protein complex that mediates innate immune responses via caspase-1 activation promoting secretion of IL-1β and IL-18 in their active forms, and also release of the high-mobility group box 1 protein (HMGB1). As the placenta seems to play an important role in the pathogenesis of PE, the present study investigated the expression of genes and proteins related to the inflammasome in placentas from pregnant women with severe preeclampsia. Placental tissue was collected from 20 normotensive pregnant women and 20 preeclamptic women, and inflammasome components, NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3), caspase-1, IL-1β and IL-18, as well as tumor necrosis factor-alpha (TNF-α) and HMGB1 were evaluated by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and also quantified by reverse transcription-qPCR (RT-qPCR). Compared with normotensive pregnant women, placenta from women with PE showed a significant increase in NLRP3, caspase-1, IL-1β, TNF-α and HMGB1 mRNA. Immunohistochemical staining of NLRP3, caspase-1, IL-1β and TNF-α in placental villi, as well as the levels of caspase-1, IL-1β, TNF-α and HMGB1 in placental homogenate were significantly higher in the preeclamptic group than in the normotensive group. However, mRNA expression of IL-18 and its protein concentrations were lower in placentas from preeclamptic women. The results suggest that placentas from pregnant women with preeclampsia show higher expression of NLRP3 inflammasome, which may be involved in the exaggerated inflammatory state in preeclampsia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Preeclampsia (PE) is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in ...its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE). We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), fms-like tyrosine-kinase-1 (Flt-1) and endoglin (Eng) levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Pre‐eclampsia (PE) is an obstetric pathology characterized by abnormal activation of the innate and adaptive immune systems dependent on the imbalance of T helper subsets. The present study ...aimed to evaluate the gene and protein expression of T helper type 1 (Th1)/Th2/Th17/regulatory T (Treg) cell transcription factors in peripheral blood lymphocytes from pregnant women with PE employing quantitative RT‐PCR and flow cytometry techniques, as well as the cytokine profile produced by these CD4+ T‐cell subsets in the plasma of pregnant women with PE, classified as early‐onset PE (n = 20), late‐onset PE (n = 20) and normotensive pregnant women (n = 20). Results showed a higher percentage of CD4+ T cells expressing the RORc transcription factor (Th17) and a lower percentage of cells expressing FoxP3 (Treg) in women with early‐onset PE compared with late‐onset PE and normotensive groups. A lower gene expression of GATA‐3 transcription factor was detected in cells of women with early‐onset PE compared with the late‐onset PE group. Endogenous plasma levels of interleukin‐6 (IL‐6), IL‐17 and tumour necrosis factor‐α were significantly higher in the early‐onset PE group than in the late‐onset PE and normotensive groups, whereas IL‐4 (Th2 profile) and IL‐22 (Th17 profile), were not significantly different between the studied groups. The endogenous levels of transforming growth factor‐β and IL‐10 were significantly lower in the pre‐eclamptic than in the normotensive groups of the same gestational age, with a significant difference between early‐ and late‐onset PE. The results show that in women with PE there is an imbalance between inflammatory and anti‐inflammatory profiles in CD4+ T‐cell subsets, with polarization to Th17 profiles in the early‐onset PE, considered as the severe form of PE.
Endogenous characterization of CD4+ T‐cell subsets by expression of the transcription factors T‐bet, RORc, GATA‐3 and FoxP3 in women with pre‐eclampsia and normotensive pregnant women. A deviation of CD4+ lymphocytes to the T helper type 17 profile was more evident in pregnant women with early‐onset pre‐eclampsia, the more severe form of this obstetric pathology.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP‐3) concentrations between women with pre‐eclampsia and healthy pregnant women. We also aimed to determine the ...relationships between circulating TIMP‐3 and matrix metalloproteinase 2 (MMP‐2), MMP‐9, TIMP‐1, and TIMP‐2 concentrations in pre‐eclampsia.
Methods
A primary case–control study included patients with pre‐eclampsia (n = 219) and gestational hypertension (n = 118), healthy pregnant women (n = 214), and non‐pregnant women (n = 66), and a replication case–control study included patients with pre‐eclampsia (n = 177) and healthy pregnant women (n = 124), all from southeastern Brazil. Plasma TIMP‐3, MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2 concentrations were assessed using commercially available enzyme‐linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation.
Results
In our primary study, patients with pre‐eclampsia and gestational hypertension exhibited increased TIMP‐3 concentrations compared with healthy pregnant women (both P < 0.0001) and non‐pregnant women (both P < 0.001). These findings were confirmed in the replication study, showing elevated TIMP‐3 concentrations in women with pre‐eclampsia versus healthy pregnant women (P < 0.001). We found no difference in TIMP‐3 concentrations between early‐onset and late‐onset pre‐eclampsia. Moreover, TIMP‐3 concentrations were significantly correlated with plasma concentrations of TIMP‐1 (r = 0.2333; P = 0.0086) and MMP‐2 (r = 0.2159; P = 0.0156) in pre‐eclampsia.
Conclusions
Circulating TIMP‐3 concentration is increased in women with pre‐eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP‐2 and TIMP‐1 concentrations in pre‐eclampsia.
Synopsis
Circulating TIMP‐3 concentration is increased in pre‐eclampsia compared with healthy pregnant women, and is positively correlated with plasma MMP‐2 and TIMP‐1 concentrations in pre‐eclampsia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Overestimation and miscalibration increase with a decrease in performance. This finding has been attributed to a common factor: participants’ knowledge and skills about the task performed. ...Researchers proposed that the same knowledge and skills needed for performing well in a test are also required for accurately evaluating one’s performance. Thus, when people lack knowledge about a topic they are tested on, they perform poorly and do not know they did so. This is a compelling explanation for why low performers overestimate themselves, but such increases in overconfidence can also be due to statistical artifacts. Therefore, whether overestimation indicates lack of awareness is debatable, and additional studies are needed to clarify this issue. The present study addressed this problem by investigating the extent to which students at different levels of performance know that their self-estimates are biased. We asked 653 college students to estimate their performance in an exam and subsequently rate how confident they were that their self-estimates were accurate. The latter judgment is known as second-order judgments (SOJs) because it is a judgment of a metacognitive judgment. We then looked at whether miscalibration predicts SOJs per quartile. The findings showed that the relationship between miscalibration and SOJs was negative for high performers and positive for low performers. Specifically, for low performers, the less calibrated their self-estimates were the more confident they were in their accuracy. This finding supports the claim that awareness of what one knows and does not know depends in part on how much one knows.
•Preeclamptic women showed high plasma levels of sTNFR1 and TNF.•Plasma from preeclamptic women induced high TNFR1 expression by Jurkat cells.•Progesterone played a modulatory role over TNFR1 ...expressed by Jurkat cells.•Progesterone shifted Jurkat cells towards an anti-inflammatory profile.
Pregnant women with preeclampsia (PE) present a shift in the immune response to an inflammatory profile. This deviation could be due to the interaction of tumor necrosis factor (TNF) with TNFR1 and TNFR2 receptors, besides the failure in modulation of inflammation regulatory mechanisms. This study evaluated the effects of progesterone on the expression of TNFR1 and TNFR2 by Jurkat cells after stimulation with plasma from PE and normotensive (NT) pregnant women. Jurkat cells were cultured with or without progesterone in a medium containing 20% (v/v) plasma from PE or NT women. The expression of TNF receptors was evaluated by flow cytometry. The concentration of soluble forms of TNF receptors and cytokines was determined in culture supernatant and plasma by ELISA. The plasma of PE women showed significantly higher concentrations of sTNFR1 and TNF and lower concentrations of sTNFR2 compared to the NT group. TNFR1 receptor expression was increased in Jurkat cells, while TNFR2 was decreased after culture with PE plasma when compared with Jurkat cells cultured with progesterone and plasma from NT women. The concentration of sTNFR1, TNF, and IL-10 in the culture supernatant of Jurkat cells was increased after culture with PE plasma, while the sTNFR2 receptor was decreased when compared to the NT group. Results demonstrate that in preeclamptic women a systemic inflammation occurs with an increase of inflammatory molecules, and progesterone may have a modulating effect on the expression of TNF receptors, shifting Jurkat cells towards an anti-inflammatory profile with greater expression of TNFR2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•DAMPs involvement in systemic inflammation of pre-eclampsia.•Hyaluronan stimulate inflammasome activation in monocytes from pre-eclamptic women.•Hsp70 induce inflammation in monocytes from ...pre-eclamptic women.
Pre-eclampsia (PE) is a human pregnancy syndrome with abnormal activation of the innate immune response. The study evaluated the involvement of molecular structures called damage-associated molecular patterns (DAMPs), such as hyaluronan (HA) and heat shock proteins (Hsp) on NLRP1 and NLRP3 inflammasomes activation in peripheral blood monocytes. Twenty pre-eclamptic women, 20 normotensive pregnant women (NT) and 20 non-pregnant women (NP) were studied. Enzyme immunoassay was employed for the determination of HA, Hsp70 and High mobility group Box 1 (HMGB1) in plasma, as well as for the detection of Interleukin-1β (IL-1β), IL-18 and tumor necrosis factor alpha (TNF-α) in the supernatant of monocytes cultured with or without HA and Hsp70. The inflammasomes induction was evaluated by the quantification of mRNA for NLRP1, NLRP3, caspase-1, IL-1β, IL-18, HMGB1 and TNF-α by qPCR in monocyte culture. The results showed significantly higher plasma levels of HA, Hsp70 and HMGB1 in pre-eclamptic women than in NT and NP women. Monocytes from women with PE showed endogenous activation of NLRP1 and NLRP3 inflammasomes, and expressed high amounts of IL-1β, IL-18, HMGB1 and TNF-α. The stimulation of monocytes with HA increased the gene expression of NLRP1, NLRP3, caspase-1, TNF-α, IL-1β, HMGB1 and IL-18 and the production of IL-1β in pre-eclamptic women. Monocytes cultured with Hsp70 produced elevated levels of IL-1β and TNF-α through a mechanism independent of inflammasomes activation. These results suggest the participation of these DAMPs in the systemic inflammatory response that is characteristic of PE.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this study, monolayers formed from organophosphonic acids were employed to stabilize porous γ-Al2O3, both as a single component and as a support for Pt nanoparticle catalysts, during exposure to ...hydrothermal conditions. To provide a baseline, structural changes of uncoated γ-Al2O3 catalysts under model aqueous phase reforming conditions (liquid water at 200 °C and autogenic pressure) were examined over the course of 20 h. These changes were characterized by X-ray diffraction, NMR spectroscopy, N2 physisorption, and IR spectroscopy. It was demonstrated that γ-alumina was rapidly converted into a hydrated boehmite (AlOOH) phase with significantly decreased surface area. Deposition of alkyl phosphonate groups on γ-alumina drastically inhibited the formation of boehmite, thereby maintaining its high specific surface area over 20 h of treatment. 27Al MAS NMR spectra demonstrated that hydrothermal stability increased with alkyl tail length despite lower P coverages. Although the inhibition of boehmite formation by the phosphonic acids was attributed primarily to the formation of Al2O3–PO x bonds, it was found that use of longer-chain octadecylphosphonic acids led to the most pronounced effect. Phosphonate coatings on Pt/γ-Al2O3 improved stability without adversely affecting the rate of a model reaction, catalytic hydrogenation of 1-hexene.
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IJS, KILJ, NUK, PNG, UL, UM
Transvaginal ultrasound revealed an evolutive 6 weeks’ gestational age intrauterine pregnancy (IUP; figure 1A) and a non-cystic extraovarian mass (58×35 mm; figure 1B,C) with surrounding fluid in the ...left adnexa (figure 1). HP is defined as the coexistence of at least two pregnancies in different implantation sites and its incidence in spontaneous pregnancies is estimated to be 1/30 000.1 Predisposing risk factors include previous history of EP, tubal surgery, pelvic inflammatory disease, use of an intrauterine device, in vitro fertilisation in the current pregnancy, in utero diethylstilbestrol exposure and smoking.2 3 The main symptoms of HP are abdominal pain, adnexal mass, peritoneal irritation and an enlarged uterus,1 which can mimic other gynaecological causes (miscarriage, EP, IUP with haemorrhagic corpus luteum and adnexal torsion) and non-gynaecological ones (appendicitis, cholecystitis, bowel obstruction or pancreatitis).4 Due to these unspecific clinical symptoms, the diagnosis of HP is often delayed and only made after a ruptured EP,1 which is associated with a considerable risk of maternal morbidity and mortality (0.50 per 100 000 live births).4 5 Despite its low sensitivity (33%) in the detection of HP, transvaginal ultrasound is the gold standard for diagnosis.6 7 Although ultrasound evaluation of an early gestation should include the adnexa, the diagnosis of an IUP often leads to the mistaken exclusion of the hypothesis of a concomitant EP.4 We present a rare case of a spontaneous HP in a woman with no obvious predisposing risk factors. Patients with no risk factors account for a minority of the cases of HP.3 Despite the low suspicion index, transvaginal ultrasound with systematic evaluation of the adnexa allowed an early diagnosis of such a rare case of HP.
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