Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances such responses. To identify a potential mechanism(s) underlying this in vivo activity of vitamin A, we examined the effects of all-trans and 9-cis RA on development of Th1 and Th2 cell populations using in vitro stimulation of Ag-naive Th0 cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, but not with all-trans RA, at primary stimulation strongly enhanced Th2 development. IL-4-neutralizing Ab blocked this activity, but IL-12- and IFN-γ-neutralizing Ab did not. Because 9-cis RA regulates gene transcription via either RA receptors or retinoid X receptors (RXRs), we tested the Th2-enhancing activities of the RXR- and RA receptor-selective agonists AGN194204 and 4-((E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TTNPB). AGN194204 strongly enhanced Th2 development, whereas TTNPB did not. This RXR agonist also enhanced Th2 development when purified, naive Th0 cells (L-selectinhigh/CD4+) were stimulated with CD3 and CD28 Abs in the absence of APCs. During primary antigenic stimulation of naive Th0 cells from DO11.10 mice, AGN194204 increased IL-4 and IL-5 production, decreased IFN-γ production, increased mRNA in responding T cells for genes involved in Th2 development (IL-4, GATA-3, and c-maf), and decreased mRNA for genes involved in Th1 development (IFN-γ, T-bet, and IL-12R). These data show that stimulation of the RXR pathway enhances Th2 development, perhaps by affecting the relative expression of pertinent transcription factors, cytokines, and cytokine receptors.
Objectives: The rapid pace, high volume, and limited quality of mental health evidence being generated during COVID-19 poses a barrier to effective decision-making. The objective of the present report is to compare mental health outcomes assessed during COVID-19 to outcomes prior to COVID-19 in the general population and other population groups. Design: Living systematic review. Data Sources: MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), EMBASE (Ovid), Web of Science Core Collection: Citation Indexes, China National Knowledge Infrastructure, Wanfang, medRxiv (preprints), and Open Science Framework Preprints (preprint server aggregator). The initial search was conducted on April 13, 2020 with ongoing weekly updates. Eligibility criteria for selecting studies: For this report, we included studies that compared general mental health, anxiety symptoms, or depression symptoms, assessed January 1, 2020 or later, to the same outcomes collected between January 1, 2018 and December 31, 2019. We required ≥ 90% of participants pre-COVID-19 and during COVID-19 to be the same or the use of statistical methods to address missing data. For population groups with continuous outcomes for at least three studies in an outcome domain, we conducted restricted maximum-likelihood random-effects meta-analyses. Results: As of March 22, 2021, we had identified 36 unique eligible studies with data from 33 cohorts. All reported COVID-19 outcomes between March and June 2020, and 3 studies also reported outcomes between September and November 2020. Estimates of changes in general mental health were close to zero in the general population (standardized mean difference [SMD] = 0.02, 95% CI -0.11 to 0.16, I2 = 94.6%; 4 studies, N = 19,707) and among older adults (SMD = 0.02, 95% CI -0.11 to 0.16, I2 = 90.4%; 4 studies, N = 5,520) and university students (SMD = -0.01, 95% CI -0.33 to 0.30, I2 = 92.0%; 3 studies, N = 3,372). Changes in anxiety symptoms were close to zero and not statistically significant in university students (SMD = 0.00, 95% CI -0.35 to 0.36, I2 = 95.4%; 5 studies, N = 1,537); women or females (SMD = 0.02, 95% CI -0.35 to 0.39, I2 = 92.3%; 3 studies, N = 2,778); and men or males (SMD = 0.07, 95% CI -0.01 to 0.15; I2 = 0.01%; 3 studies, N = 1,250); anxiety symptoms increased, however, among people with pre-existing medical conditions (SMD = 0.27, 95% CI 0.01 to 0.54, I2 = 91.0%; 3 studies, N = 2,053). Changes in depression symptoms were close to zero or small and not statistically significant among university students (SMD = 0.19, 95% CI -0.08 to 0.45, I2 = 91.8%; 5 studies, N = 1,537); people with pre-existing medical conditions (SMD = 0.01, 95% CI -0.15 to 0.17, I2 = 14.9%; 3 studies, N = 2,006); women or females (SMD = 0.21, 95% CI -0.14 to 0.55, I2 = 91.2%; 3 studies, N = 2,843); and men or males (SMD = 0.00, 95% CI -0.21 to 0.22; I2 = 92.3%; 4 studies, N = 3,661). In 3 studies with data from both March to June 2020 and September to November 2020, symptoms were unchanged from pre-COVID-19 at both time points or there were increases at the first assessment that had largely dissipated by the second assessment. Conclusions: Evidence does not suggest a widespread negative effect on mental health symptoms in COVID-19, although it is possible that gaps in data have not allowed identification of changes in some vulnerable groups. Continued updating is needed as evidence accrues.
Caffeoylquinic acids (CQAs) are a broad class of secondary metabolites that have been found in edible and medicinal plants from various families. It has been 100 years since the discovery of chlorogenic acid in 1920. In recent years, a number of naturally derived CQAs have been isolated and structurally elucidated. Accumulated evidence demonstrate that CQAs have a wide range of biological activities, such as antioxidation, antibacterial, antiparasitic, neuroprotective, anti-inflammatory, anticancer, antiviral, and antidiabetic effects. Up to date, some meaningful progresses on the biosynthesis and total synthesis of CQAs have also been made. Therefore, it is necessary to comprehensively summarize the structure, biological activity, biosynthesis, and chemical synthesis of CQAs. This review provides extensive coverage of naturally occurring CQAs discovered from 1990 until 2020. Modern isolation techniques, chemical data (including structure, biosynthesis, and total synthesis), and bioactivity are summarized. This would be helpful for further research of CQAs as potential pharmaceutical agents.
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