Abstract Pathological hypoxia/oxidative stress of placenta is a major cause in preeclampsia. Autophagy dysregulation has recently been linked to aberrant placental vascular function in preeclampsia [1, 2] while the underlying mechanisms remain unknown. Here, we found exosomal TINCR derived from trophoblasts exposed to hypoxia-oxidative stress induced placental vascular dysfunction through evoking excessive autophagic activation of endothelial cells related to preeclampsia. Specifically, umbilical cord serum- and plasma-derived exosomal TINCR levels were elevated in preeclampsia determined by microarray-based transcript analyses and qRT-PCR, which may be caused by trophoblasts releasing exosomes containing TINCR into circulation under pathological hypoxia conditions of the placenta. These exosomal TINCR impaired placental vascular function by promoting excessive autophagy of endothelial cells involved in preeclampsia-like symptoms both in vivo and in vitro. In contrast, the autophagy inhibitor hydroxychloroquine (HCQ) partially reversed exosomal TINCR's effect on placental vascular dysfunction and preeclampsia symptoms. Mechanistically, TINCR promoted autophagy in endothelial cells by regulating miR-424/ ATG5 axis as a competing endogenous RNA. Therefore, preeclampsia was associated with the overactivation of endothelial cell autophagy by trophoblast-derived exosomal TINCR in regulating placental vascular function, indicating that targeting autophagy such as HCQ is a novel strategy for preeclampsia treatment.
Decidual CD8+ (dCD8) T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS) signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8) T counterparts. Furthermore, human dCD8 T cells were observed to contain CD8-Treg and effector-memory T-cell subsets, and display enhanced functionality in terms of degranulation and cytokine production on a per-cell basis. Additionally, we have identified the novel splice junctions that use a high ratio of the non-canonical splicing motif GC-AG and found that AS is not a major contributor to the gene expression-level changes between paired pCD8 and dCD8 T cells. Together, our findings not only provide a comprehensive framework of the transcriptional and AS landscapes but also reveal the functional feature of human dCD8 T cells, which are of great importance in understanding the biology of these cells and the physiology of human healthy pregnancy.
Coherent backlight is an essential component for holographic displays. In this paper, a compact design of edge-lit coherent backlight featuring two holographic optical elements for two-dimensional beam expansion is presented. Its diffraction efficiency is numerically studied using the coupled-wave theory. In experiments, the diffraction efficiency is measured as 4.3% and the feasibility of this design is verified by reconstructing 3D images with a spatial light modulator.
Background/Aims: Increasing evidence shows that oxidative stress plays an important part in the pathophysiological mechanisms of preeclampsia (PE). Polymorphic variants of oxidative stress-related candidate genes GST1 and GPX1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the associational analysis between GSTP1 and GPX1 single nucleotide polymorphisms (SNPs) and susceptibility to PE in Chinese Han women. Methods: DNA from 1130 PE patients and 1226 healthy individuals was genotyped for SNPs rs1695 in GSTP1 and rs1050450 in GPX1 using a predesigned TaqMan SNP genotyping assay. The χ2 test compared differences in genetic distributions between the two groups in a case-control study. Results: No significant differences in allelic or genotypic frequencies of GSTP1 rs1695 or GPX1 rs1050450 were detected between cases and controls (GSTP1 rs1695: χ2=1.122, p=0.571 by genotype, χ2=0.138, p=0.710, odds ratio=1.027, 95% confidence interval 0.892-1.183 by allele; GPX1 rs1050450: χ2=0.036, p=0.982 by genotype, χ2=0.002, p=0.960, odds ratio=1.005, 95% confidence interval 0.822-1.229 by allele). Moreover, no significant differences in genetic distribution were found between early/late-onset PE or mild/severe PE and control subgroups. Conclusion: Our results suggest that GSTP1 rs1695 and GPX1 rs1050450 SNPs have no effects on the risk of PE in the Chinese Han population. However, these results should be confirmed by replication in different populations.
A miniature static Fourier transform spectrometer (MSFTS) as the component of coherent discriminating laser warning receiver (CDLWR) was designed in the present study by using a modified wedge interfering etalon (MWIE), a linear charge couple device (CCD) and a fast digital signal processor (DSP). The MSFTS possesses some advantages such as small volume, low cost, high speed, stable performance and good signal to noise ratio. MSFTS can detect the spectrum of HIPL, the short pulse width of laser is about 10 ns, and the spectrum scope is from 400 to 1 100 nm. The key element of MSFTS is MWIE which is composed of two triangle prisms, one of which is a right angle prism with two equal acute angles of 45 degrees, another prism has no right angle, one of the acute angles is 45 degrees, and another is slightly smaller than 45 degrees. The long sides of the two prisms were bonded by transparent glass glue, and the adhesive surface is plated with special material which serves as a beam splitter (BS). The incident laser will be split into two equal strength beams with continuously changing optical path difference, the two beams will interfere and form interferogram which will be focused by a cylinder as a line and transformed as s electronic signal by CCD. The electronic signal was processed by using a DSP, and finally we obtained the spectrum of the incident hostile laser by applying fast Fourier transform (FFT). We have established the experiment system of MSFTS, and used the system and the spectrometer Q8344A made by Advantest Company in Japan to measure the spectra of the seven lasers with different central wavelengths: 635, 650, 670, 780, 808, 850 and 980 nm. The measurement result shows that the worst wavelength resolution is 8. 845 nm at 1 100 nm, the best wavelength resolution is 1.170 nm at 400 nm, the relative average error of central wavelength is 0.269 nm, the absolute average error is 0.919 nm and signal-to-noise ratio of our experiment system is better than that of Q8344A.
Lupus nephritis (LN) is one of most common secondary glomerulonephritis. There is no ideal method to simultaneously assess renal structure and function in patients with LN. The aim of this study is to investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) MR imaging in the assessment of renal involvement and pathological changes in patients with LN. Sixty-five patients with LN and 16 healthy volunteers underwent coronal echo-planar DWI and BOLD MR imaging of the kidneys. The apparent diffusion coefficient (ADC) and R2* values of the kidneys were calculated with b values of 0 and 500 s/mm2. The relationship between the renal injury variables and the ADCs or R2* values were evaluated. And 16 of 65 patients with LN underwent a repeated evaluation after the induction treatment for 9 to 12 months. The mean ADC values of kidneys in patients with LN were 2.40 ± 0.25 × 10-3 mm2/ s, the mean R2* values of the renal cortex and medulla were 11.03 ± 1.60/sec and 14.05 ± 3.38/sec respectively, which were all significantly lower than that in volunteers. In patients with LN, the mean ADC values were correlated with eGFR (r = 0.510, p < 0.01). There was a negative correlation between the mean ADC values and renal pathology chronicity indexes (r = -0.249, p < 0.05), the R2* values of the renal medulla and proteinuria (r = -0.244, p < 0.05), and the degree of tubulointerstitial lesions (r = -0.242, p < 0.05). The ADC and R2* values of kidneys were significantly higher than those of pre-treatment in complete remission patients. DWI and BOLD MR imaging of kidneys may be used to noninvasively monitor the disease activity and evaluate therapeutic efficacy in lupus nephritis.
Abstract Multiple pieces of evidence illustrate that impaired trophoblast function results in preeclampsia (PE), and migration/invasion of human trophoblast cells is stringently regulated by extracellular matrix (ECM) components. Many studies have indicated abnormal expressions of placental ECM components are associated with preeclampsia. However, the change and influence of lumican, a vital member of extracellular matrix (ECM) molecules, on trophoblast cells during preeclampsia remain unclear. This study examines the possibility that the roles of lumican in trophoblast cells contribute to PE. To address this issue, the expression of lumican in human placental tissues was observed using immunohistochemistry, fluorescence quantitative PCR, and Western blot technology. After the HTR-8/SVneo cell line was transfected with pcDNA3.1-human lumican, pGPU6-human lumican shRNA, and their negative controls, the impact of lumican on the HTR-8/SVneo cell line was investigated. Lumican was expressed in human placental tissues. Compared with the control group, its expression was significantly lower in PE placentas. Lumican downregulation inhibited cell proliferation significantly and reduced Bcl-2 expression, but increased P53 expression. These results indicate that the downregulation of placental lumican may drive PE development via promoting the downregulation of Bcl-2 expression and upregulation of P53.
Purpose To noninvasively monitor carotid plaque vulnerability by exploring the relationship between pharmacokinetic parameters (PPs) of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and plaque types based on MRI‐modified American Heart Association (AHA) classification, as well as to assess the ability of PPs in discrimination between stable and vulnerable plaques suspected on MRI. Materials and Methods Of 70 consecutive patients with carotid plaques who volunteered for 3.0T MRI (3D time‐of‐flight [TOF], T 1 ‐weighted, T 2 ‐weighted, 3D magnetization‐prepared rapid acquisition gradient‐echo [MP‐RAGE] and DCE‐MRI), 66 participants were available for analysis. After plaque classification according to MRI‐modified AHA Lesion‐Type (LT), PPs ( K trans , k ep , v e , and v p ) of DCE‐MRI were measured. The Extended Tofts model was used for calculation of PPs. For participants with multiple carotid plaques, the plaque with the worst MRI‐modified AHA LT was chosen for analysis. Correlations between PPs and plaque types and the ability of these parameters to distinguish stable and vulnerable plaques suspected on MRI were assessed. Results Significant positive correlation between K trans and LT III to VI was found (ρ = 0.532, P < 0.001), as was the correlation between k ep and LT III to VI (ρ = 0.409, P < 0.001). Stable and vulnerable plaques suspected on MRI could potentially be distinguished by K trans (sensitivity 83%, specificity 100%) and k ep (sensitivity 77%, specificity 91%). Conclusion K trans and k ep from DCE‐MRI can provide quantitative information to monitor plaque vulnerability in vivo and differentiate vulnerable plaques suspected on MRI from stable ones. These two parameters could be adopted as imaging biomarkers for plaque characterization and risk stratification. Level of Evidence : 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:870–876
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