Influence of synthetic superparamagnetic iron oxide on dendritic cells

Yongbin Mou1, Baoan Chen2, Yu Zhang3, Yayi Hou4, Hao Xie4, Guohua Xia2, Meng Tang5, Xiaofeng Huang1, Yanhong Ni1, Qingang Hu1,6 1Central Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, 2Department of Hematology, Zhongda Hospital, Medical School, Southeast University, 3State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, 4Immunology and Reproductive Biology Laboratory, Medical School, Nanjing University, 5Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China; 6Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, UK Background: This study investigated the influence of synthetic superparamagnetic iron oxide (SPIO) on dendritic cells and provides a possible method for labeling these cells. Methods: SPIO nanoparticles were prepared, and their morphology and magnetic properties were characterized. The particles were endocytosed by dendritic cells generated from mouse bone marrow. Labeling efficiency and cellular uptake were analyzed by Prussian blue staining and quantitative spectrophotometric assay. Meanwhile, the surface molecules, cellular apoptosis, and functional properties of the SPIO-labeled dendritic cells were explored by flow cytometry and the mixed lymphocyte reaction assay. Results: The synthetic nanoparticles possessed a spherical shape and good superparamagnetic behavior. The mean concentration of iron in immature and mature dendritic cells was 31.8 ± 0.7 µg and 35.6 ± 1.0 µg per 1 × 106 cells, respectively. After 12 hours of incubation with SPIO at a concentration of 25 µg/mL, nearly all cells were shown to contain iron. Interestingly, cellular apoptosis and surface expression of CD80, CD86, major histocompatibility II, and chemokine receptor 7 in mature dendritic cells were not affected to any significant extent by SPIO labeling. T cell activation was maintained at a low ratio of dendritic cells to T cells. Conclusion: SPIO nanoparticles have good superparamagnetic behavior, highly biocompatible characteristics, and are suitable for use in further study of the migratory behavior and biodistribution of dendritic cells in vivo. Keywords: superparamagnetic iron oxide, dendritic cell, cell labelin

MicroRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells,”

Abstract PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral arteries. The present study was performed to determine the function of miR-29b (microRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin β1) genes by directly binding to their 3 -UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE

Mevalonate Diphosphate Decarboxylase MVD/Erg19 Is Required for Ergosterol Biosynthesis, Growth, Sporulation and Stress Tolerance in Aspergillus oryzae

Mevalonate diphosphate decarboxylase (MVD; EC 4.1.1.33) is a key enzyme of the mevalonic acid (MVA) pathway. In fungi, the MVA pathway functions as upstream of ergosterol biosynthesis, and MVD is also known as Erg19. Previously, we have identified Aoerg19 in Aspergillus oryzae using bioinformatic analysis. In this study, we showed that AoErg19 function is conserved using phylogenetic analysis and yeast complementation assay. Quantitative reverse transcription–PCR (qRT-PCR) indicated that Aoerg19 expression changed in different growth stages and under different forms of abiotic stress. Subcellular localization analysis showed that AoErg19 was located in the vacuole. Overexpression of Aoerg19 decreased the ergosterol content in A. oryzae, which may due to the feedback-mediated downregulation of Aoerg8. Consistent with the decrease in ergosterol content, both Aoerg19 overexpression and RNAi strains of A. oryzae are sensitive to abiotic stressors, including ergosterol biosynthesis inhibitor, temperature, salt and ethanol. Thus, we have identified the function of AoErg19 in A. oryzae, which may assist in genetic modification of MVA and the ergosterol biosynthesis pathway

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses

Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust

Differential expression of microRNAs in the placentae of Chinese patients with severe pre-eclampsia

Background: The pathogenesis of pre-eclampsia (PE) is incompletely understood. The placenta is considered to play a key role in this disease. Recent research showed that many microRNAs (miRNAs) are expressed in human placenta. Our aim in this study was to determine differential expression of miRNAs in placenta with severe PE, and normal placenta. Methods: Differential expression of miRNAs in placenta (four severe PE and a control group of four normal pregnant women) was first screened using microarray analysis. Following this, some differential miRNAs were selected and validated using real-time quantitative reverse transcription-polymerase chain reaction in placenta from women with severe PE (n=24), and a healthy control group (n=26). Results: We found the following miRNAs were significantly increased in placenta from women with severe PE: miR-16, miR-29b, miR-195, miR-26b, miR-181a, miR-335 and miR-222. Gene ontology analysis of the target genes revealed enrichment for specific biological process categories, i.e., regulation of cellular physiological process including miR-16, miR-29b, miR-195, miR-26b and miR-335, and signal transduction including miR-181a and miR-222. Conclusions: These different miRNAs may play an important role in pathogenesis of PE and may become diagnostic markers for PE. Clin Chem Lab Med 2009;47:923–9.Peer Reviewe

Circulating Irisin Level and Thyroid Dysfunction: A Systematic Review and Meta-Analysis

Both thyroid hormones and irisin have profound influences on the metabolism of the human body. Based on their similarities, several studies have been conducted to explore changes in irisin levels in patients with hypothyroidism and hyperthyroidism. This study was conducted in accordance with the PRISMA statement and the MOOSE reporting guideline. Based on a preregistered protocol (PROSPERO—CRD42019138430), a comprehensive search of eight databases was performed from inception to April 2020. Studies with original data collected from patients with thyroid dysfunction were included. Subgroup analysis was performed based on the different types of clinical manifestations and patient characteristics. The quality of each study and the presence of publication bias were assessed by the Newcastle-Ottawa score (NOS) and funnel plot with Egger’s test, respectively. A total of 11 studies with 1210 participants were included. Ten studies were identified as high-quality studies. Pooled analysis indicated decreased irisin levels in patients with hypothyroidism (MD -10.37, 95% CI -17.81 to -2.93). Subgroup analysis revealed an even lower level of irisin in patients with clinical-type hypothyroidism (MD -17.03, 95% CI -30.58 to -3.49) and hypothyroidism caused by autoimmune disease (MD -19.38, 95% CI -36.50 to -2.26). No differences were found after achieving euthyroid status from levothyroxine treatment in patients with hypothyroidism compared with controls. No differences were found between patients with hyperthyroidism and controls. Correlation analyses revealed a possible negative correlation between irisin and TSH and positive correlations between irisin and both fT3 and fT4. Irisin was correlated with TSH receptor antibodies

Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review

Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future

Rumor Detection With Hierarchical Representation on Bipartite Ad Hoc Event Trees

The rapid growth of social media has caused tremendous effects on information propagation, raising extreme challenges in detecting rumors. Existing rumor detection methods typically exploit the reposting propagation of a rumor candidate for detection by regarding all reposts to a rumor candidate as a temporal sequence and learning semantics representations of the repost sequence. However, extracting informative support from the topological structure of propagation and the influence of reposting authors for debunking rumors is crucial, which generally has not been well addressed by existing methods. In this article, we organize a claim post in circulation as an ad hoc event tree, extract event elements, and convert it into bipartite ad hoc event trees in terms of both posts and authors, i.e., author tree and post tree. Accordingly, we propose a novel rumor detection model with hierarchical representation on the bipartite ad hoc event trees called BAET. Specifically, we introduce word embedding and feature encoder for the author and post tree, respectively, and design a root-aware attention module to perform node representation. Then we adopt the tree-like RNN model to capture the structural correlations and propose a tree-aware attention module to learn tree representation for the author tree and post tree, respectively. Extensive experimental results on two public Twitter datasets demonstrate the effectiveness of BAET in exploring and exploiting the rumor propagation structure and the superior detection performance of BAET over state-of-the-art baseline methods