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In biology, structure is the basis of function. For plants, changes in their physiological and ecological functions are usually caused by structural changes. To understand how shading conditions change the plant structures, thereby providing structural insights into the improved yield and quality, oilseed tree peony were shaded with different densities of polyethylene nets from 28 days after pollination (DAP) until harvesting. The thickness of the leaf (LT), vein (VT), upper epidermis (UET), lower epidermis (LET), palisade tissue (PT), sponge tissue (ST), as well as the accumulation and distribution of starch, protein, and fat, were observed at 14-day intervals. The results showed that shading had a significant effect on the anatomical structure of the leaves. In the rapid growth period (before 70 DAP), the LT, ET, and VT under shading were significantly lower than under non-shading. During this period, the accumulation of starch and protein under shading was lower than that under non-shading. At the maturation period (99–112 DAP), the LT and PT under shading were higher than under non-shading, indicating that light shading delayed leaf senescence and increased photosynthetic capacity. Shading delayed the degradation of the integument cells and prolonged seed development and nutrient accumulation.

Kawasaki disease (KD) is an acute systemic vasculitis that mainly afflicts infants and young children. The symptoms of KD are similar to those of various febrile diseases. Here, we attempted to develop accurate diagnostic biomarkers of KD by performing urine proteomic analysis of samples from healthy controls, patients with KD, and patients with another febrile disease, pneumonia (two patients). We identified differentially expressed proteins (DEPs) in KD as compared to normal controls. We also constructed functional annotation and protein-protein interaction (PPI) networks of DEPs in KD and pneumonia. DEPs common to both KD and pneumonia were identified, as well as DEPs specific to KD. Compared to normal control, 43 and 62 DEPs were identified in KD and pneumonia, respectively. Serine hydroxymethyltransferase 1 is a hub protein of the KD-specific PPI network. Thirteen DEPs common to both KD and pneumonia and 30 DEPs specific to KD were identified. Of these, the expression of eight DEPs could cluster normal and pneumonia samples into one group and cluster KD samples into another group based on hierarchical clustering. Our study identified several DEPs that may play a role in KD and that may serve as diagnostic biomarkers to distinguish patients with KD from both normal control and other febrile diseases.

Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPR

The objectives of this study were to determine (1) the longitudinal profile of plasma soluble ST2 (sST2) concentrations in patients with preeclampsia and those with uncomplicated pregnancies; (2) whether the changes in sST2 occur prior to the diagnosis of preeclampsia; and (3) the longitudinal sST2 profile of women with early or late preeclampsia.This longitudinal nested case-control study included singleton pregnancies in the following groups: (1) uncomplicated pregnancies (n = 160); and (2) those complicated by early (34 weeks, n = 9) and late (≥34 weeks, n = 31) preeclampsia. sST2 concentrations were determined by enzyme-linked immunosorbent assays. Mixed-effects models were used for the longitudinal analysis.(1) Plasma sST2 concentration profiles across gestation differed significantly among cases and controls (p 0.0001); (2) women with early preeclampsia had higher mean sST2 concentrations than controls at22 weeks of gestation; cases with late preeclampsia had higher mean concentrations at33 weeks of gestation (both p 0.05); and (3) these changes started approximately 6 weeks prior to clinical diagnosis.Maternal plasma sST2 concentrations are elevated 6 weeks prior to the clinical diagnosis of preeclampsia. An increase in the maternal plasma concentration of sST2 may contribute to an exaggerated intravascular inflammatory response and/or the Th1/Th2 imbalance in some cases.

Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This sine qua non of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different “omics,” clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. Moreover, first trimester maternal blood from preterm preeclamptic patients in vitro dysregulated trophoblastic gene expression. Placental transcriptomics of women with preterm preeclampsia identified distinct gene modules associated with maternal or fetal disease. Placental “virtual” liquid biopsy showed that the dysregulation of these disease gene modules originates during the first trimester. In vitro experiments on hub transcription factors of these gene modules demonstrated that DNA hypermethylation in the regulatory region of ZNF554 leads to gene down-regulation and impaired trophoblast invasion, while BCL6 and ARNT2 up-regulation sensitizes the trophoblast to ischemia, hallmarks of preterm preeclampsia. In summary, our data suggest that there are distinct maternal and placental disease pathways, and their interaction influences the clinical presentation of preeclampsia. The activation of maternal disease pathways can be detected in all phenotypes of preeclampsia earlier and upstream of placental dysfunction, not only downstream as described before, and distinct placental disease pathways are superimposed on these maternal pathways. This is a paradigm shift, which, in agreement with epidemiological studies, warrants for the central pathologic role of preexisting maternal diseases or perturbed maternal–fetal–placental immune interactions in preeclampsia. The description of these novel pathways in the “molecular phase” of preeclampsia and the identification of their hub molecules may enable timely molecular characterization of patients with distinct preeclampsia phenotypes.

Objective: Preterm birth is associated with 5–18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated AF IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection and those destined to deliver spontaneously before term among women with preterm labor and intact membranes. Methods: One-hundred thirty-six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6 ≥ 2600 pg/ml. Results: (1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%) and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745 pg/ml; (2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta and patients at risk of impending spontaneous preterm delivery. Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20 min – this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.

Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0.1), abnormal uterine artery Doppler velocimetry (p = 0.7) or whether diagnosis was made before or after 34 weeks gestational age (p = 0.3); (3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [sVEGFR-1: Spearman rho 0.34, p = 0.001 and sEng: Spearman rho 0.30, p = 0.003]; (4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p = 0.004), as well as uncomplicated pregnancies (p = 0.001); and (5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the “great obstetrical syndromes”; each p > 0.05). Conclusion: Median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction.

Ongoing low-grade inflammation and endothelial dysfunction persist in children with coronary lesions diagnosed with Kawasaki disease (KD). Statins, frequently used in the management of high cholesterol, have also shown to improve surrogate markers of inflammation and endothelial dysfunction. This study was undertaken to investigate the efficacy and safety of pravastatin in children with coronary artery aneurysms due to KD.The study enrolled 14 healthy children and 13 male children, aged 2-10 years, with medium-to-giant coronary aneurysms for at least 12 months after the onset of KD. Pravastatin was given orally to the KD group at a dose of 5 mg/day for children under 5 and 10 mg/day for children older than 5 years. To determine the effects of pravastatin on endothelial function, high-frequency ultrasound was performed before the start of the study and 6 months after pravastatin therapy. The parameters measured were brachial artery flow-mediated dilation (FMD), non-flow mediated dilation (NMD), and carotid artery stiffness index (SI). High sensitive C-reactive protein (hs-CRP) levels, the circulating endothelial progenitor cells (EPCs) number, and serum lipid profiles were also determined at baseline and after 6 months of pravastatin treatment.Before treatment, the KD group had significantly decreased FMD (P0.05) and increased SI and hs-CRP levels (P0.05) compared with controls. After 6 months of pravastatin therapy, FMD improved significantly compared to the baseline KD group (3.16±6.49 to 10.05±7.74, P0.05), but remained significantly less than that in the control group with no significant changes in NMD and SI. There were significant decreases in markers of inflammation after treatment. The hs-CRP levels decreased significantly from 2.93±0.81 mmol/L to 2.14±0.82 mmol/L (P0.05) and the serum apo-B and apo-B/apo-A1 ratio were also reduced (P0.05) in the KD group. However, the circulating EPC number was not significantly different between baseline and that following pravastatin treatment in the KD group and the control group (P0.05). No significant complications were noted with paravastatin therapy.Pravastatin improves endothelial function and reduces low-grade chronic inflammation in patients with coronary aneurysms due to KD. Children with coronary aneurysms due to KD may benefit from statin therapy.

Preeclampsia (PE) is characterized by systemic intravascular inflammation. Women who develop PE are at an increased risk for cardiovascular disease in later life. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has anti-atherosclerotic effects in endothelial cells and can mediate neutrophil apoptosis. Low soluble TRAIL (sTRAIL) and high C-reactive protein (CRP) concentrations are associated with an increased risk of future cardiovascular disease in non-pregnant individuals. The aim of this study was to determine whether maternal plasma concentrations of sTRAIL and CRP differ between women with PE and those with uncomplicated pregnancies.This cross-sectional study included women with an uncomplicated pregnancy (n = 93) and those with PE (n = 52). Maternal plasma concentrations of sTRAIL and CRP concentrations were determined by ELISA.1) The median plasma sTRAIL concentration (pg/mL) was significantly lower and the median plasma CRP concentration was significantly higher in women with PE than in those with an uncomplicated pregnancy (25.55 versus 29.17; p = 0.03 and 8.0 versus 4.1; p = 0.001, respectively); 2) the median plasma concentration sTRAIL/CRP ratio was two-fold lower in women with PE than in those with an uncomplicated pregnancy (p 0.001); and 3) women with plasma sTRAIL and CRP ratio in the lowest quartile were 8 times more likely to have PE than women with concentrations in the upper three quartiles (OR 8.9; 95% CI: 2.8-27.8).Maternal plasma sTRAIL concentrations are lower (while those of CRP are higher) in women with PE than in those with uncomplicated pregnancies. These findings are consistent with the evidence of intravascular inflammation in this disorder.

Objective: The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM). Methods: A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA. Results: i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P Conclusions: Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers.

Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.This cross-sectional study included women with preeclampsia (n = 106) and women with an uncomplicated pregnancy (n = 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.(1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p = 0.7 and p = 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho = 0.72 and 0.63; each p0.0001), and negatively with PlGF (Spearman's Rho = -0.56, p0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.

The mechanisms for the heat-induced osteogenesis are not completely known and the thermal regulation of human mesenchymal stem cell (hMSC) differentiation is not well studied. In this study, the direct effects of mild heat shock (HS) on the differentiation of hMSCs into osteoblasts in self-assembling peptide hydrogel and on tissue culture plates were investigated. hMSCs isolated from human bone marrow were seeded in conventional culture plates (two-dimensional [2D] culture) and on the surface of three-dimensional (3D) PuraMatrix peptide hydrogel (3D culture), followed by 1 h HS at 41°C once a week during osteogenic differentiation. Alkaline phosphatase (ALP) activity was enhanced in both 2D and 3D cultures via periodic HS at early stage of differentiation; meanwhile, HS significantly increased the calcium deposition at day 19 and 27 of differentiation in both 2D and 3D cultures. The periodic HS also upregulated osteo-specific genes, osterix (OSX) on day 11, osteopontin (OP) on day 19, and bone morphogenetic protein 2 (BMP2) on day 25 in 2D culture. In 3D PuraMatrix culture, the runt-related transcription factor 2 (Runx2) was upregulated by HS on day 25 of differentiation. The heat shock protein 70 (HSP70) was significantly upregulated by HS in differentiated hMSCs analyzed at 24 h after HS. These results demonstrate that HS induced an earlier differentiation of hMSCs and enhanced the maturation of osteoblasts differentiated from hMSCs. Therefore, mild HS treatment may be potentially used to enhance the bone regeneration using hMSCs. Our data will guide the design of in vivo heating protocols and enable further investigations in thermal treatments of MSC osteogenesis for bone tissue engineering.

To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and -2 could identify patients at risk for developing preeclampsia (PE) requiring preterm delivery.Patients presenting with the diagnosis "rule out PE" to the obstetrical triage area of our hospital at37 weeks of gestation (n = 87) were included in this study. Delivery outcomes were used to classify patients into four groups: I) patients without PE or those with gestational hypertension (GHTN) or chronic hypertension (CHTN) who subsequently developed PE at term (n = 19); II): mild PE who delivered at term (n = 15); III): mild disease (mild PE, GHTN, CHTN) who subsequently developed severe PE requiring preterm delivery (n = 26); and IV): diagnosis of severe PE (n = 27). Plasma concentrations of PlGF, sEng, sVEGFR-1 and -2 were determined at the time of presentation by ELISA. Reference ranges for analytes were constructed by quantile regression in our laboratory (n = 180; 1046 samples). Comparisons among groups were performed using multiples of the median (MoM) and parametric statistics after log transformation. Receiver operating characteristic curves, logistic regression and survival analysis were employed for analysis.The mean MoM plasma concentration of PlGF/sVEGFR-1, PlGF/sEng, PlGF, sVEGFR-1 and -2, and sEng in Group III was significantly different from Group II (all p0.05). A plasma concentration of PlGF/sVEGFR-1 ≤ 0.05 MoM or PlGF/sEng ≤0.07 MoM had the highest likelihood ratio of a positive test (8.3, 95% CI 2.8-25 and 8.6, 95% CI 2.9-25, respectively), while that of PlGF ≤0.396 MoM had the lowest likelihood ratio of a negative test (0.08, 95% CI 0.03-0.25). The association between low plasma concentrations of PlGF/sVEGFR-1 (≤0.05 MoM) as well as that of PlGF/sEng (≤0.07 MoM) and the development of severe PE remained significant after adjusting for gestational age at presentation, average systolic and diastolic blood pressure, and a history of chronic hypertension [adjusted odds ratio (OR) = 27 (95% CI 6.4-109) and adjusted OR 30 (95% CI 6.9-126), respectively]. Among patients who presented34 weeks gestation (n = 59), a plasma concentration of PlGF/sVEGFR-10.033 MoM identified patients who delivered within 2 weeks because of PE with a sensitivity of 93% (25/27) and a specificity of 78% (25/32). This cut-off was associated with a shorter interval-to-delivery due to PE [hazard ratio = 6 (95% CI 2.5-14.6)].Plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in the obstetrical triage area. These observations support the value of these biomarkers in the clinical setting for the identification of the patient at risk for disease progression requiring preterm delivery.

Problem To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). Method of Study This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. Results (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. Conclusion Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis.

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from 6 groups (n=396) were studied: nonpregnant and pregnant women with normal term delivery, term and preterm preeclampsia, and term and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term delivery were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in nonpregnant women (38.7 versus 9.2 ng/mL; P P =0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases ( P

Background During vascular injury, vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) are exposed to altered luminal blood flow or transmural interstitial flow. We investigate the effects of these two types of fluid flows on the phenotypes of SMCs and MFBs and the underlying mechanotransduction mechanisms. Methodology/principal findings Exposure to 8 dyn/cm(2) laminar flow shear stress (2-dimensional, 2-D) for 15 h significantly reduced expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle protein 22 (SM22), SM myosin heavy chain (SM-MHC), smoothelin, and calponin. Cells suspended in collagen gels were exposed to interstitial flow (1 cmH(2)O, approximately 0.05 dyn/cm(2), 3-D), and after 6 h of exposure, expression of SM-MHC, smoothelin, and calponin were significantly reduced, while expression of alpha-SMA and SM22 were markedly enhanced. PD98059 (an ERK1/2 inhibitor) and heparinase III (an enzyme to cleave heparan sulfate) significantly blocked the effects of laminar flow on gene expression, and also reversed the effects of interstitial flow on SM-MHC, smoothelin, and calponin, but enhanced interstitial flow-induced expression of alpha-SMA and SM22. SMCs and MFBs have similar responses to fluid flow. Silencing ERK1/2 completely blocked the effects of both laminar flow and interstitial flow on SMC marker gene expression. Western blotting showed that both types of flows induced ERK1/2 activation that was inhibited by disruption of heparan sulfate proteoglycans (HSPGs). Conclusions/significance The results suggest that HSPG-mediated ERK1/2 activation is an important mechanotransduction pathway modulating SMC marker gene expression when SMCs and MFBs are exposed to flow. Fluid flow may be involved in vascular remodeling and lesion formation by affecting phenotypes of vascular wall cells. This study has implications in understanding the flow-related mechanobiology in vascular lesion formation, tumor cell invasion, and stem cell differentiation.

Objective To investigate placental protein 13 (PP13) localization in relation to cytoskeleton and lipid rafts in preeclampsia and HELLP syndrome. Study Design Placental cryosections from patients with preeclampsia and HELLP, and controls were stained for PP13, actin, PLAP (lipid raft marker), and CD71 (nonraft marker). BeWo cells exposed to stress conditions were stained for PP13 and actin. Protein localizations were investigated by confocal microscopy, PP13 concentrations by ELISA. Results PP13-actin colocalization was increased in syncytiotrophoblast juxtamembrane regions in term/preterm preeclampsia and HELLP. PP13-CD71 colocalization was decreased and PP13-PLAP proximity was increased in preterm but not term preeclampsia and HELLP. PP13-release from BeWo cells was inhibited by cytoskeleton disruption, and augmented by Ca 2+ -influx and ischemic stress. Conclusion The actin cytoskeleton, probably in connection with lipid rafts, controls trophoblastic "nonclassical" PP13 export. PP13 is released from the syncytiotrophoblast in preterm preeclampsia and HELLP, mimicked in BeWo cells by ischemic stress, suggesting PP13 is a placental alarmin.

The aim of this study was to examine if maternal plasma concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-2 change prior to the diagnosis of preeclampsia.A longitudinal study was conducted in normal pregnant women (n = 160) and patients with preeclampsia (n = 40). Blood samples were collected at 7 gestational age intervals from 6 weeks to term. Plasma concentrations of sVEGFR-2 were determined by enzyme-linked immunosorbent assay. Analysis was performed with cross-sectional and longitudinal (mixed effects model) approaches.Mothers destined to develop preeclampsia have lower plasma sVEGFR-2 concentrations than those who will have a normal pregnancy (longitudinal approach; P.05). Cross-sectional analysis suggested that the median plasma sVEGFR-2 concentration in women destined to develop preeclampsia was significantly lower than that in normal pregnant women from 28-31 weeks of gestation (P = .001) or 6-10 weeks prior to the diagnosis (P.001).A lower maternal plasma sVEGFR-2 concentration precedes the development of preeclampsia, both term and preterm.

To study the relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B.One hundred and fifty-seven patients with chronic hepatitis B were included in the study, 49 patients among them were diagnosed as early cirrhosis by liver biopsy. Serum HBV DNA levels were determined using fluorescent quantitative PCR, and serum hepatic fibrosis markers including hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III precollagen (P III P) and type IV collagen (IV-C) were determined by radioimmunity assay. The relationship between serum HBV DNA levels and hepatic fibrosis markers were analyzed. Serum HBV DNA levels and hepatic fibrosis markers of 49 patients with early cirrhosis were compared with those of 108 non-cirrhotic patients.There was no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B (P0.05). Patients with early cirrhosis had much higher hepatic fibrosis markers together with lower HBV DNA levels than non-cirrhotic patients (P0.05).There were no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in patients with chronic hepatitis B.

The prevalence of viral infections in the amniotic fluid (AF) has not yet been ascertained. The aim of this study was to determine the prevalence of specific viral nucleic acids in the AF and its relationship to pregnancy outcome.From a cohort of 847 consecutive women undergoing midtrimester amniocentesis, 729 cases were included in this study after exclusion of documented fetal anomalies, chromosomal abnormalities, unavailability of AF specimens and clinical outcomes. AF specimens were tested by quantitative real-time PCR for the presence of genome sequences of the following viruses: adenoviruses, herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), parvovirus B19 and enteroviruses. Viral nucleic acid testing was also performed in maternal blood and cord blood in the population of women in whom AF was positive for viruses and in a control group of 29 women with AF negative for viral nucleic acids. The relationship between the presence of viruses and pregnancy and neonatal outcome was examined. The correlation between the presence of nucleic acids of viruses in the AF and the concentration of the cytokine interleukin-6 (IL-6) and the T cell chemokine CXCL-10 (or IP-10) in AF and maternal blood were analyzed.Viral genome sequences were found in 16 of 729 (2.2%) AF samples. HHV6 was the most commonly detected virus (7 cases, 1.0%), followed by HCMV (6 cases, 0.8%), parvovirus B19 (2 cases, 0.3%) and EBV (1 case, 0.1%), while HSV, VZV, enteroviruses and adenoviruses were not found in this cohort. Corresponding viral DNA was also detected in maternal blood of six out of seven women with HHV6-positive AF and in the umbilical cord plasma, which was available in one case. In contrast, viral DNA was not detected in maternal blood of women with AF positive for parvovirus B19, HCMV, EBV or of women with AF negative for viruses. HHV6 genome copy number in AF and maternal blood was consistent with genomic integration of viral DNA and genetic infection in all women. There was no significant difference in the AF concentration of IL-6 and IP-10 between patients with and without VIAC. However, for HCMV, there was a significant relationship between viral copy number and IP-10 concentration in maternal blood and AF. The group of women with AF positive for viral DNA delivered at term healthy neonates without complications in 14 out of 16 cases. In one case of HHV6 infection in the AF, the patient developed gestational hypertension at term, and in another case of HHV6 infection in the AF, the patient delivered at 33 weeks after preterm premature rupture of membranes (PPROM).Viral nucleic acids are detectable in 2.2% of AF samples obtained from asymptomatic women in the midtrimester. HHV6 was the most frequently detected virus in AF. Adenoviruses were not detected. Vertical transmission of HHV6 was demonstrated in one case.

To investigate the clinical usefulness of noninvasive diagnostic methods in evaluating liver fibrosis in hepatitis B virus (HBV) patients.102 patients with chronic hepatitis B (CHB) were enrolled from Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences. Noninvasive diagnostic methods including ultrasonography, CT, serum markers of liver function and fibrosis, and HBV DNA were performed and compared with histological fibrotic changes in order to establish a noninvasive method for detecting the degree of liver fibrosis.The total score of liver surface, edge, parenchyma echogenicity, intrahepatic vessels, and the size of spleen had a coefficient of 0.822 with fibrotic stage. By receiver operating curve (ROC) analysis, the sensitivity to distinguish cirrhosis from CHB was 86.1% and the specificity was 95.5% if the total ultrasonic score was more than 10. The CT imaging diagnosed liver cirrhosis with a specificity of 100% and a sensitivity of 48.5%. The change of CT values in cirrhotic patients was lower than that in controls and no cirrhotic patients (F=5.805, P0.01), when the voltage was increased from 100 KV to 140 KV. Except normal controls and S1 group, S2 and S3 group, the level of HA and collagen IV between the other groups were statistically different. The cut-off value of HA to diagnose cirrhosis was 108 (microg/L) with a sensitivity of 72.2% and a specificity of 80.3%. The cut-off value of collagen IV to diagnose cirrhosis was 188 (microg/L) with a sensitivity of 72.2% and a specificity of 78.8%. When ultrasonography was combined with serum markers, the sensitivity was 72.2% and the specificity was 80.3%.Both ultrasonography and serum markers are useful to diagnose cirrhosis. The combination of the two examinations is more valuable than any one alone. The characteristic CT imaging has high specificity but low sensitivity in diagnosing early cirrhosis. HA and collagen IV are correlated more closely with the stage of fibrosis, and can reflect the severity of fibrosis.

To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30-34 weeks of gestation can identify patients at risk for stillbirth, late preeclampsia, and delivery of small-for-gestational-age (SGA) neonates.A prospective cohort study included 1269 singleton pregnant women from whom blood samples were obtained at 30-34 weeks of gestation and who delivered at34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by enzyme-linked immunosorbent assay.The prevalence of late (34 weeks of gestation) preeclampsia, severe late preeclampsia, stillbirth, and SGA was 3.2% (n = 40), 1.8% (n = 23), 0.4% (n = 5), and 8.5% (n = 108), respectively. A plasma concentration of PlGF/sEng0.3 MoM was associated with severe late preeclampsia (adjusted odds ratio, 16); the addition of PlGF/sEng to clinical risk factors increased the area under the receiver-operating characteristic curve from 0.76 to 0.88 (P = .03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20-25 weeks of gestation for the prediction of severe late preeclampsia (comparison of areas under the receiver-operating characteristic curve; each P ≤ .02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false-positive rate of 15% for the identification of severe late preeclampsia. A plasma concentration of PlGF/sVEGFR-10.12 MoM at 30-34 weeks of gestation had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80%; specificity 93%) were observed in a separate case-control study.Risk assessment for stillbirth and severe late preeclampsia in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and antiangiogenic factors at 30-34 weeks of gestation.