Christensenputnam4446

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.AIM There is limited data on the combined use of more than one biologic or small molecule in the treatment of patients with inflammatory bowel disease. METHODS We identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and small molecule from 2015 to 2019 for persistent disease activity or concomitant rheumatologic or dermatologic disease. 3-deazaneplanocin A supplier The primary endpoint was effectiveness based on improvement in inflammatory markers, clinical, and endoscopic remission. The secondary endpoint was safety. RESULTS Among 50 patients treated with combination therapy, there were significantly more patients in clinical and endoscopic remission at follow up, 50% vs 14%, p=0.0018, delta 36%; 95% CI 0.13-0.53, and 34% vs 6%, p=0.0039, delta 28%, 95% CI 0.09-0.47 respectively. Median ESR (17 vs 13, p=0.002) and CRP (5 vs 2.35, p=0.002) also decreased post-treatment. There were 8 serious adverse events and no deaths. Of those with a serious adverse event, 57% were also on an immunomodulator vs 17.4% of those without a serious adverse event, p=0.019. CONCLUSIONS Combination biologic therapy appears to be an effective option for inflammatory bowel disease patients with refractory disease or concomitant autoimmune disease inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared to biologic monotherapy, however this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Larger prospective studies are needed to confirm these findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symtoms of SARS-CoV-2 and the subsequent prognosis is worsened in individuals who have pre-exisiting comorbidities prior to infection by the virus. Individuals with obesity/overweight, insulin resistance and diabetes typically have chronic low-grade inflammation characterized by increased levels of several pro-inflammatory cytokines and the inflammasome this state predisposes to greater risk for infection along with more adverse outcomes. Here we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune-protection against Covid-19 by attenuating the "cytokine storm syndrome" often experienced by "at risk" individuals. This article is protected by copyright. All rights reserved.Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIMS/INTRODUCTION To evaluate gestational weight gain (GWG) in the first and second trimester as a risk factor for gestational diabetes mellitus (GDM) among women pregnant with singletons. MATERIALS AND METHODS This was a cohort study of women with singleton pregnancies who delivered between January 1, 2013 and October 31, 2014 in a Chinese hospital. We collected data from medical records from the first antenatal visit to delivery. All pregnant women were subjected to an oral glucose tolerance test (OGTT) for diagnosis of GDM during the second trimester. GWG in the first and second trimester was calculated by subtracting pre-pregnancy weight from weight within 4 weeks of OGTT. We categorized GWG into insufficient, appropriate, and excessive according to the Institute of Medicine (IOM) guidelines and population quantiles. Univariable and multivariable analyses was used to determine the association between GWG and GDM risk. RESULTS Of 10,422 pregnant women, we identified 8356 eligible women with 1622 (19.4%) diagnosed with GDM.