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Hepatitis B virus (HBV) RNA in serum is a novel biomarker that reflectscccDNA activity. We investigated whether HBV RNA can predict serological response topeginterferon (PEG-IFN) treatment.Serum HBV RNA levels were retrospectively measured at weeks 0, 12, 24, and 52 of therapy and after treatment discontinuation (week 78) in 266 HBeAg-positive chronic HBV patients who had participated in a global randomized controlled trial (HBV99-01 study). Patients received 52 weeks PEG-IFN monotherapy (n=136) orPEG-IFN and lamivudine (n=130). The primary endpoint was HBeAg loss 24 weeks after PEG-IFN discontinuation.At baseline, the mean serum level of HBV RNA was 6.8 (SD 1.2) log c/mL.HBV RNA levels declined to 4.7 (1.7) log c/mL after one year of PEG-IFN therapy alone and to 3.3 (1.2)log c/mLafter combination therapy. From week 12 onward, HBV RNA level was significantly lower in patients who achieved HBeAg loss at the end of follow-up as compared to those who did not, regardless of treatment allocation (week 12 4.4 vs. 5.1 log c/mL, p=0.01; week 24 3.7 vs. 4.9 log c/mL, p less then 0.001). The performance of a multivariable model based on HBV RNA levelwas comparable at week 12 (AUC 0.68)and 24 (AUC 0.72) of therapy. HBV RNA level above 5.5 log c/mL at week 12 showed negative predictive values of 93/67/90/64% for HBV genotypes A/B/C/D for the prediction of HBeAg loss. In conclusion, HBV RNA in serum declines profoundly during PEG-IFN treatment. Early on-treatment HBV RNAlevel may be used to predict non-response. This article is protected by copyright. All rights reserved.BACKGROUND Glutathione S-transferases omega class 1 (GSTO1-1) is a unique member of the GST family regulating cellular redox metabolism and innate immunity through the promotion of LPS/TLR4/NLRP3 signalling in macrophages. House dust mite (HDM) triggers asthma by promoting type 2 responses and allergic inflammation via the TLR4 pathway. Although linked to asthma, the role of GSTO1-1 in facilitating type 2 responses and/or HDM-driven allergic inflammation is unknown. OBJECTIVE To determine the role of GSTO1-1 in regulating HDM-induced allergic inflammation in a preclinical model of asthma. METHODS Wild-type and GSTO1-1-deficient mice were sensitized and aeroallergen challenged with HDM to induce allergic inflammation and subsequently hallmark pathophysiological features characterized. RESULTS By contrast to HDM-challenged WT mice, exposed GSTO1-1-deficient mice had increased numbers of eosinophils and macrophages and elevated levels of eotaxin-1 and -2 in their lungs. M1 macrophage-associated factors, such as poxia and the regulation of the severity of allergic inflammation in asthma. © 2020 John Wiley & Sons Ltd.It has been accepted knowledge that placebo effects have been significant in insomnia clinical trials. However, the dynamic features of placebo effects have not been clarified. Our aim was therefore to conduct a meta-analysis of placebo-controlled randomized clinical trials to characterize the dynamic features of placebo effects addressing persistent insomnia disorder. We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of therapeutic regimens addressing persistent insomnia disorder. We pooled separate effect size estimates (Hedge's g) of placebo and regimen conditions across trials for outcome measures, and multilevel mixed-effects models were used to explore potential sources of heterogeneity. The placebo effects were significant and robust to improve the symptoms of insomnia, and subjective measures were significantly smaller than objective measures (p less then .001), but placebo response rates were nearly identical between subjective and objective measures. The overall placebo effects were influenced by publication year (p = .015), treatment duration (p = .010), sample size (p less then .001) and therapeutic regimen (p less then .001). Placebo effects showed a diphasic feature within treatment duration initially a decrease and subsequently being stable; a sustained decline trend after withdrawals; and a steady-to-upward trend for a mixed therapeutic regimens in a large-scale period over decades. The dynamic features of placebo effects addressing persistent insomnia disorder may lead to the development and validation of dosing strategies that require less medication exposure to maintain clinical effects. © 2020 European Sleep Research Society.NEW FINDINGS What is the central question of this study? We explored the role of miR-143-3p during hDPSC differentiation. What is the main finding and its importance? 1. miR-143-3p negatively regulates RANK. 2. RANKL binds to RANK and stimulates the development of osteoclasts. 3. OPG inhibits the interaction between RANK and RANKL. 4. OPG/RANKL signaling pathway regulates odontogenic differentiation of hDPSCs. ABSTRACT Background and Objective Human dental pulp stem cells (hDPSCs) are capable of differentiating into odontoblast-like cells, which secrete reparative dentin after injury, in which the role of microRNA-143-3p (miR-143-3p) has been identified. Therefore, we investigated the mechanism by which miR-143-3p influences odontoblastic differentiation of hDPSCs. Methods The relationship between miR-143-3p and RANK was initially identified by bioinformatics prediction and further verified by dual luciferase reporter gene assay. Gain- and loss-of-function analysis with miR-143-3p mimic and miR-143-3p inhibiton of the mechanisms of odontogenic differentiation of hDPSCs may contribute to the development of effective dental pulp repair therapies for the clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.In bacteria, guanosine (penta)tetra-phosphate ([p]ppGpp) is essential for controlling intracellular metabolism that is needed to adapt to environmental changes, such as amino acid starvation. The (p)ppGpp0 strain of Bacillus subtilis, which lacks (p)ppGpp synthetase, is unable to form colonies on minimal medium. Here, we found suppressor mutations in the (p)ppGpp0 strain, in the purine nucleotide biosynthesis genes, prs, purF and rpoB/C, which encode RNA polymerase core enzymes. In comparing our work with prior studies of ppGpp0 suppressors, we discovered that methionine addition masks the suppression on minimal medium, especially of rpoB/C mutations. Furthermore, methionine addition increases intracellular GTP in rpoB suppressor and this effect is decreased by inhibiting GTP biosynthesis, indicating that methionine addition activated GTP biosynthesis and inhibited growth under amino acid starvation conditions in (p)ppGpp0 backgrounds. Furthermore, we propose that the increase in intracellular GTP levels induced by methionine is due to methionine derivatives that increase the activity of the de novo GTP biosynthesis enzyme, GuaB. Our study sheds light on the potential relationship between GTP homeostasis and methionine metabolism, which may be the key to adapting to environmental changes. © 2020 John Wiley & Sons Ltd.This work describes a synthetic approach where a non-planar aromatic heterocyclic [7]helicene is compressed to yield a hetero[8]circulene containing an inner antiaromatic cyclooctatetraene (COT) core. This [8]circulene consists of four benzene rings and four heterocyclic rings, and it is the first heterocyclic [8]circulene containing three different heteroatoms. The synthetic pathway proceeds via a the flattened dehydro-hetero[7]helicene, which is partially a helicene and partially a circulene it is non-planar and helically chiral as helicenes, and contains a COT motif like [8]circulenes. The antiaromaticity of the COT core is confirmed by nucleus independent chemical shift (NICS) calculations. The planarization from a helically p-conjugated [7]helicene to a fully planar heterocyclic [8]circulene significantly alters the spectroscopic properties of the molecules. Post-functionalization of the [7]helicenes and the [8]circulenes by oxygenation of the thiophene rings to the corresponding thiophene-sulfones allows an almost complete fluorescence emission coverage of the visible region of the optical spectrum (400-700 nm). © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION Various biopsychosocial factors affect women's preferences with respect to mode of birth, but they are usually not examined simultaneously and prospectively. In the current study, we assessed the contribution of personal characteristics of first-time mothers, their prior prenatal perceptions, events during birth, and subjective birth experiences, on their preference about mode of second birth. METHODS This was a secondary analysis of two prospective birth cohort studies. Participants included 832 primiparous women recruited mostly from women's health centers in Israel, and through natural birth communities and cesarean birth websites. Women completed questionnaires prenatally and were followed up at 6-8 weeks postpartum to understand their preferences for a second birth. RESULTS Regression models indicated that after vaginal first birth, being less religious, believing that birth is a medical process, and having a negative experience increased the odds of preferring primary cesarean for the second birth. After cesarean birth, being more religious, having higher education, conceiving spontaneously, having a more negative birth experience, and perceiving better treatment from the staff during birth contributed to preferring vaginal birth for the second birth. CONCLUSIONS Religiosity is central to women's preferences, probably because of its association with the desire to have many children. Modifiable factors, such as women's beliefs about the nature of birth, their overall birth experience, and their perceived treatment from the staff, could influence the uptake of having vaginal births. Intrapartum care that is empathic and encouraging, along with education about modes of birth, could help decrease cesarean birth rates. © 2020 Wiley Periodicals, Inc.The connection between circular RNAs (circRNAs) and gastric cancer has been reported widely in recent years. However, previous studies have focused mainly on circRNAs from gastric cancer tissue. The objectives of the present study were to detect dysregulated circRNAs from both tissue and plasma of patients with gastric cancer and to explore their potential roles in the pathogenesis of gastric cancer. Expression profiles of circRNAs were obtained from the Gene Expression Omnibus (GEO) and analyzed using the GEO2R tool to identify differential expressed circRNAs. The significance threshold was set as |log2 (fold change)| > 2 and adjusted P  less then  .05. The microRNA (miRNA) binding sites of the differentially expressed circRNAs were predicted using the Circular RNA Interactome web tool. TargetScan and the miRNet database were used to predict the miRNA target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using Database for Annotation Visualization and Integrated Discovery. Hub genes were identified and a network was constructed with Cytoscape. The overall survival rates for the selected miRNAs and messenger RNAs were evaluated by Kaplan-Meier Plotter. A total of three downregulated circRNAs (hsa_circ_0001190, hsa_circ_0036287, and hsa_circ_0048607) were identified in this study. Six miRNAs and eight hub genes met the significance criteria and were selected for further analysis. A circRNA-miRNA-hub gene network was constructed based on three circRNAs, six miRNAs, and eight hub genes. Evaluation of overall survival rates for the hub genes showed that low expression levels of GADD45A, PPP1CB, PJA2, and KLF2 were associated with poor overall survival. This study identified potential novel plasma circRNA biomarkers and provides insights into the underlying mechanisms of gastric cancer pathogenesis. © 2020 Wiley Periodicals, Inc.
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