Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.495
Filtrar
1.
J Formos Med Assoc ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33012636

RESUMO

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33041005

RESUMO

The nucleotide-binding domain and leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome is involved in various acute and chronic liver diseases, however, it is not clear whether NLRP3 contributes to d-Galactosamine (D-GalN) plus lipopolysaccharide (LPS)-induced acute liver failure (ALF). This study aims to investigate the role of NLRP3 inflammasome in D-GalN/LPS-induced fatal hepatitis. We found that Nlrp3-/- and WT mice showed similar mortality against a lethal dose of D-GalN/LPS treatment. Serum ALT and AST levels, as well as liver necrosis area and hepatocyte apoptosis, were not significantly different between Nlrp3-/- and WT mice at 6 h after D-GalN/LPS injection. Moreover, the numbers of intrahepatic F4/80+ cells and Ly6G+ cells were comparable in two genotype mice following D-GalN/LPS treatment. Besides, Nlrp3-/- mice had reduced IL-1ß levels but similar TNF-α, IL-6, and MCP-1 levels compared with WT mice upon D-GalN/LPS administration. Our findings revealed that NLRP3 ablation does not protect mice from D-GalN/LPS-induced fatal hepatitis and has a marginal effect on intrahepatic inflammatory response upon D-GalN/LPS treatment. This suggests that NLRP3 inflammasome does not appear to be a major contributor to D-GalN/LPS-induced ALF.

3.
Dig Dis Sci ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043405

RESUMO

BACKGROUND: Endoplasmic reticulum stress (ERS) has been studied as critical factor during occurrence and development of ulcerative colitis (UC). However, the role of ERS in inflamed UC remains unclear. AIMS: The purpose of this study was to analyze the role of inositol-requiring kinase 1 (IRE-1), a major regulator of ER, in regulating ERS and cell viability. METHODS: In UC mucosa tissue, IRE-1, BiP, XBP-1s, CHOP caspase-12 and GADD34 mRNA were assayed by qRT-PCR. Then, human normal colon epithelial cell line (NCM-460) and colon fibroblast cell line (CCD-33Co) were cultured, and downregulated or upregulated IRE-1 expression. ERS was induced with 100 ng/mL of Interleukin 6 (IL-6). CCK8 assay was performed to analyze cell proliferation. Flow cytometry analysis was conducted to detect the apoptosis. Western blot assay was used to examine ERS markers. RESULTS: IRE-1, BiP, XBP-1s, caspase-12 and CHOP mRNA were highly expressed in UC mucosa tissue, and the expression of GADD34 mRNA significantly decreased. These results show that ERS-induced unfolded protein response was enhanced in UC mucosa tissue. In cells, silencing the expression of IRE-1 could suppress cell proliferation and promote apoptosis through activating unfolded protein response, while the over-expression of IRE-1 had the opposite effect. IL-6 could induce ERS and cells apoptosis. Furthermore, we demonstrated that shRNA IRE-1 could enhance the inhibition of IL-6 on cells viability. CONCLUSIONS: Inhibition of IRE-1 enhanced unfolded protein response and cells apoptosis and IL-6-induced ERS and suggested that IRE-1 might be a potential target of UC.

4.
Anesth Analg ; 131(5): 1412-1418, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33079864

RESUMO

In 2018, the American Board of Anesthesiology (ABA) became the first US medical specialty certifying board to incorporate an Objective Structured Clinical Examination (OSCE) into its initial certification examination system. Previously, the ABA's staged examination system consisted of 2 written examinations (the BASIC and ADVANCED examinations) and the Standardized Oral Examination (SOE). The OSCE and the existing SOE are now 2 separate components of the APPLIED Examination. This report presents the results of the first-year OSCE administration. A total of 1410 candidates took both the OSCE and the SOE in 2018. Candidate performance approximated a normal distribution for both the OSCE and the SOE, and was not associated with the timing of the examination, including day of the week, morning versus afternoon session, and order of the OSCE and the SOE. Practice-based Learning and Improvement was the most difficult station, while Application of Ultrasonography was the least difficult. The correlation coefficient between SOE and OSCE scores was 0.35 ([95% confidence interval {CI}, 0.30-0.39]; P < .001). Scores for the written ADVANCED Examination were modestly correlated with scores for the SOE (r = 0.29 [95% CI, 0.25-0.34]; P < .001) and the OSCE (r = 0.15 [95% CI, 0.10-0.20]; P < .001). Most of the candidates who failed the SOE passed the OSCE, and most of the candidates who failed the OSCE passed the SOE. Of the 1410 candidates, 77 (5.5%) failed the OSCE, 155 (11.0%) failed the SOE, and 25 (1.8%) failed both. Thus, 207 (14.7%) failed at least 1 component of the APPLIED Examination. Adding an OSCE to a board certification examination system is feasible. Preliminary evidence indicates that the OSCE measures aspects of candidate abilities distinct from those measured by other examinations used for initial board certification.

5.
Nature ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057195

RESUMO

Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone1,2. Here we characterize cell-type-specific cis-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity-termed super-interactive promoters-are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific cis-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.

6.
Nanoscale ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057564

RESUMO

The development of highly efficient and robust biomimetic catalysts is an essential and feasible strategy to overcome the intrinsic drawbacks of natural enzymes. Inspired by the synthetic strategy of covalent organic frameworks, we adopted a covalent-bond-driven strategy to prepare polyoxometalate (POM) based open frameworks (NKPOM-OFs = Nankai University POM-OFs) with abundant Mo[double bond, length as m-dash]O groups that can mimic the active center of sulfite oxidase. Four 2-dimensional (2D) NKPOM-OFs were designed and synthesized via the condensation reaction of linear amino-containing POMs with planar tetra-aldehyde monomers. Benefitting from the high crystallinity, the structures of 2D POM-OFs can be successfully determined from structural simulations. The results unveiled that NKPOM-OFs possessed 2D staggered stacking layered structures with the sql topology. All these NKPOM-OFs exhibited high crystallinity and stability and demonstrated outstanding performance to serve as biomimetic catalysts of sulfite oxidase with good recyclability. Notably, exfoliation of NKPOM-OFs under ultrasonic treatment can significantly boost the catalytic activity with almost two times faster reaction rates. This study not only enriches the facile and versatile synthesis strategy for POM-OFs but also provides new biomimetic platforms for biocatalysis.

7.
J Phys Chem Lett ; : 9203-9209, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058662

RESUMO

All-inorganic perovskites of CsPbBr3 nanocrystals (NCs) exhibit strong X-ray absorption and have been demonstrated to be highly efficient scintillators for X-ray detection and imaging. However, the long-term stability of the perovskite remains a major hurdle in practical applications, especially under a commercial dose of X-ray irradiation (0.5-5.5 mGy·s-1). Herein, with a solution-protected annealing approach reconstructing the CsPbBr3 NCs free from undesired defects, the perovskite scintillators provide a long-term (∼3600 s) stable visualization tool for X-ray radiography (1.44 × 106 captured images for the exposure time of 2.5 ms per image) under the irradiation dose of 1 mGy·s-1. This work opens a window for the stability of perovskite scintillators and demonstrates their robust and long-term efficient radioluminescence (RL) for low-cost radiography and X-ray imaging application.

8.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1092-1099, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059806

RESUMO

OBJECTIVE: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). CONCLUSIONS: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

9.
Mol Nutr Food Res ; : e2000452, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078870

RESUMO

SCOPE: The over-activation of the nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of ulcerative colitis (UC). Chlorogenic acid (CGA) exposure has been identified as an effective strategy for repressing inflammatory responses. METHODS AND RESULTS: In this study, we used the NLRP3 inflammasome model with LPS/ATP-induced RAW264.7 cells in vitro and dextran-sulfate-sodium-induced colitis in mice to evaluate the effect of CGA on NLRP3 inflammasome-related signaling. The results suggested that CGA suppressed the expression of NLRP3 inflammasome-related genes (ASC, Caspase-1 p45, Caspase-1 p20, pro-/cleaved-IL-1ß, pro-/cleaved-IL-18), p-NF-κB protein, and miR-155 in mice with colitis. Gain- and loss- of-function studies of miR-155 were performed to elucidate its role in inflammation. Moreover, activation of the NF-κB/NLRP3 inflammasome pathway and miR-155 expression were investigated. CGA exposure in LPS/ATP-stimulated RAW264.7 cells led to a decrease in p-NK-κB and NLRP3 inflammasome-related proteins, which was dependent on the downregulation of miR-155 expression. CONCLUSIONS: These findings indicate that CGA prevented colitis by downregulating miR-155 expression and inactivating the NF-κB/NLRP3 inflammasome pathway in macrophages. The current study may have promising therapeutic implications in the treatment of ulcerative colitis. This article is protected by copyright. All rights reserved.

10.
Vet Pathol ; : 300985820953500, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016243

RESUMO

Mouse kidney parvovirus (MKPV), also known as murine chapparvovirus (MuCPV), is an emerging, highly infectious agent that has been isolated from laboratory and wild mouse populations. In immunocompromised mice, MKPV produces severe chronic interstitial nephropathy and renal failure within 4 to 5 months of infection. However, the course of disease, severity of histologic lesions, and viral shedding are uncertain for immunocompetent mice. We evaluated MKPV infections in CD-1 and Swiss Webster mice, 2 immunocompetent stocks of mice. MKPV-positive CD-1 mice (n = 30) were identified at approximately 8 weeks of age by fecal PCR (polymerase chain reaction) and were subsequently housed individually for clinical observation and diagnostic sampling. Cage swabs, fecal pellets, urine, and blood were evaluated by PCR at 100 and 128 days following the initial positive test, which identified that 28 of 30 were persistently infected and 24 of these were viremic at 100 days. Histologic lesions associated with MKPV in CD-1 (n = 31) and Swiss mice (n = 11) included lymphoplasmacytic tubulointerstitial nephritis with tubular degeneration. Inclusion bodies were rare; however, intralesional MKPV mRNA was consistently detected via in situ hybridization within tubular epithelial cells of the renal cortex and within collecting duct lumina. In immunocompetent CD-1 mice, MKPV infection resulted in persistent shedding of virus for up to 10 months and a mild tubulointerstitial nephritis, raising concerns that this virus could produce study variations in immunocompetent models. Intranuclear inclusions were not a consistent feature of MKPV infection in immunocompetent mice.

11.
BMJ Open ; 10(10): e037307, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067278

RESUMO

INTRODUCTION: Cognitive impairment, an important complication in patients with chronic obstructive pulmonary disease (COPD), seriously affects self-management of the disease and quality of life (QoL). As an exercise-based intervention programme, pulmonary rehabilitation (PR)-especially aerobic exercise (mainly mind-body exercise) and resistance exercise (RE)-has been proposed for its potential effectiveness in improving cognitive function. However, there is still a lack of strong evidence for PR's effectiveness. In this study, we expect to clarify the effects of pulmonary-based Qigong exercise and elastic band-based RE on cognitive function in patients with COPD and to fill in the relevant evidence blanks. METHODS AND ANALYSIS: This study is a single-centre randomised controlled trial with assessor and data analyst blinding. We will recruit 108 participants with stable COPD starting on 23 December 2019, and randomly allocate them into the pulmonary-based Qigong exercise group, elastic band-based RE group, pulmonary-based Qigong exercise and elastic band-based RE combined group, or control group at a 1:1:1:1 ratio. Participants in intervention groups will perform 30 min of exercise two times per day, 5 days a week, for 12 weeks. The primary outcome will be the global cognitive function as assessed by the Montreal Cognitive Assessment and auditory event-related potential P300. Secondary outcomes will include the specific cognitive domains-attention, memory, executive function, verbal fluency and mental-processing speed; psychological functions and QoL. Exploratory outcomes will include grey matter volume and levels of inflammatory mediators. Outcomes will be measured before and after the interventions. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Ethics Committee of Yue-Yang Integrative Medicine Hospital, an affiliate of Shanghai University of Traditional Chinese Medicine, Shanghai, China (Grant No. 2019-141). Written informed consent will be obtained from each participant before any procedures are performed. The findings will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900026869; pre-results.

12.
Front Immunol ; 11: 2150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072079

RESUMO

The mechanism(s) underlying endotoxin tolerance in asthma remain elusive. As the endotoxin lipopolysaccharide (LPS) affects the expression of the regulatory T-cell (Treg)-suppressive glucocorticoid-induced tumor necrosis factor receptor ligand (GITRL) on antigen-presenting dendritic cells (DCs), we hypothesized that LPS-induced changes in DC GITRL expression may impact Treg-mediated T-helper (Th) cell suppression and the induction of endotoxin tolerance. Here, we propose a novel mechanism by which low-dose LPS inhalation in neonatal mice induces endotoxin tolerance, thereby offering protection from later asthma development. Three-day old wild-type and Toll-like receptor 4 (TLR4)-deficient neonatal mice were exposed to low-dose LPS (1 µg) intranasally for 10 consecutive days prior to ovalbumin (OVA)-induced asthma to better understand the tolerogenic mechanism(s) of low-dose LPS pre-exposure. In vivo findings were validated using in vitro co-culturing studies of primary CD11c+ DCs and CD4+ T-cells with or without low-dose LPS pre-exposure before OVA stimulation. Low-dose LPS pre-exposure upregulated the Treg response and downregulated pathogenic Th2 and Th17 responses through promoting apoptosis of Th2 and Th17 cells. Low-dose LPS pre-exposure downregulated DC GITRL expression and T-cell GITR expression. Artificial DC GITRL expression abrogated the tolerogenic Treg-skewing effect of low-dose LPS pre-exposure. Low-dose LPS pre-exposure inhibited TRIF/IRF3/IFNß signaling and upregulated expression of tolerogenic TRIF/IRF3/IFNß negative regulators in a TLR4-dependent manner. This tolerogenic DC GITRL downregulation was attributable to TRIF/IRF3/IFNß signaling inhibition. Low-dose LPS pre-exposure produces tolerogenic Treg skewing in neonatal asthmatic mice, a phenomenon attributable to TLR4-dependent TRIF/IRF3/IFNß-mediated DC GITRL downregulation.

13.
Environ Res ; 192: 110300, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33038368

RESUMO

Airborne particulate matter (PM) is a complex mixture containing various kinds of harmful components. Exposure to air PM is associated with childhood respiratory disease, but epidemiological data are limited concerning the circulating respiratory injury protein on the etiology of childhood respiratory disease. Specifically, the role of PM toxic components or its biological effective dose (adduct) in respiratory injury remains unclear. To demonstrate the dose-response relationship and the main mechanism on circulating club cell secretory protein (CC16) from PM compositions among children, we enrolled 273 boarding schoolchildren in China, including 110 and 163 children of whom were in the low- and high-PM exposed areas, respectively. In this study, we measured the internal exposure levels, including serum polycyclic aromatic hydrocarbons (PAH) adduct, urinary metals, and AhR expression, and detected the serum CC16 level as a lung injury marker. Environmental tobacco exposure in children was assessed by urinary cotinine. We found that significantly higher levels of serum CC16, benzo[a]pyridin-7,8-dihydroglycol-9,10-epoxide (BPDE)-albumin adduct, urinary molybdenum, selenium, arsenic, cadmium and barium, and lower level of AhR expression in high-PM exposed group. There was a good association between serum BPDE-albumin adduct and CC16 (ß = 0.222, P = 0.006). There was no association on urinary metals and serum CC16. BPDE-albumin adduct was directly associated with serum CC16 alternation [direct effect = 0.2044, 95% confidence interval (CI) = (0.0426, 0.36)]. PM could cause serum CC16 increased in children. PAH and its adduct might play a key role in lung injury during PM exposure.

14.
Shanghai Kou Qiang Yi Xue ; 29(4): 350-354, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33089280

RESUMO

PURPOSE: To investigate the expression and significance of chemokines CCL21, E-selectins and heat shock protein 90 (Hsp90) in periodontal tissues of rats with experimental periodontitis. METHODS: Forty 10-week-old male Wistar rats were significantly randomly divided into 4 groups with 10 rats in each group. Periodontitis models were established in groups A, B and C, and the rest were 10 blank control groups. Rats in group A, B and C were sacrificed at 4, 8 and 12 weeks after basic periodontal treatment, and the periodontal tissues of the first and second molars were taken for CCL21, E-selectins and Hsp90 protein expression detection. SPSS 25.0 software package was used to analyze the data. RESULTS: The levels of periodontal attachment in group A, B and C were higher than those in the control group(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 mRNA and protein expression in periodontal tissues increased first and then decreased(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 mRNA and protein expression in group B and C were significantly higher than those in group A(P<0.05). The levels of periodontal attachment, CCL21, E-selectins, Hsp90 and relative protein expression in periodontal tissues of group C were significantly lower than those of group B(P<0.05). CONCLUSIONS: The expression of CCL21, E-selectins and Hsp90 is up-regulated in periodontitis tissues. With local periodontal treatment, the expression level of CCL21, E-selectins and Hsp90 gradually decreases.


Assuntos
Selectina E , Periodontite , Animais , Masculino , Dente Molar , Periodontite/genética , Periodonto , Ratos , Ratos Wistar
15.
Front Cell Infect Microbiol ; 10: 581404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072630

RESUMO

Human coronaviruses, which can cause a range of infectious diseases, have been studied for nearly 60 years. The field has gained renewed interest from researchers around the world due to the COVID-19 outbreak in late 2019. Despite a large amount of research, little is known about the knowledge structure and developing trends of this topic. Here, we apply bibliometric analysis along with visualization tools to analyze 15,207 publications related to human coronavirus from the Scopus database, using indicators on publication and citation, journal, country or territory, affiliation and international cooperation, author, and keyword co-occurrence cluster. The results show that research on human coronavirus is dominated by SARS-CoV. Although there have been many publications, only 626 publications (4.1% of total) have more than 100 citations. The top 20 journals with most publications account for 20.6% of total publications and 41% of total citations. In addition to the United States and some European countries, many Asian and African countries are involved in this research, with China holding an important position in this area. Leading researchers from various fields of human coronavirus research are listed to facilitate collaboration and promote effective disease prevention and control. The keywords co-occurrence analysis reveals that the research focus on virology, public health, drugs and other hotspot fields, and uncovers changes in the direction of coronavirus research. The research map on human coronavirus obtained by our analysis are expected to help researchers to efficiently and effectively explore COVID-19.

16.
Occup Environ Med ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097673

RESUMO

OBJECTIVES: Susceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker's pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies. METHODS: To systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study. RESULTS: Interestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10-4) and lung function (rs4651005, OR=1.39, p=1.62×10-3; rs985256, OR=0.73, p=8.24×10-4 and rs6539952, OR=1.28, p=4.32×10-4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10-4), ANGPTL1 (rs4651005, p=5.4 ×10-7), SPATS2L (rs985256, p=1.1 ×10-5) and RP11-463O9.9 (rs6539952, p=7.1 ×10-6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis. CONCLUSIONS: These results provided a deeper understanding of the genetic predisposition basis of CWP.

17.
Chem Commun (Camb) ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052367

RESUMO

The introduction of phosphine oxide into a fluorescein scaffold has yielded phospha-fluorescein with bathochromically shifted spectra, reliable photostability and solubility. Moreover, ratiometric and turn-on fluorescence in the decaging process has ensured that the phospha-fluorescein is a unique scaffold for fluorescence bioimaging. Probe DiMe-PF-Gal without further structural decoration was designed for accurately monitoring ß-galactosidase in vivo.

18.
Int J Mol Sci ; 21(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008047

RESUMO

UDP-glycosyltransferases (UGTs) play key roles in modulating plant development and responses to environmental challenges. Previous research reported that the Arabidopsis UDP-glucosyltransferase 74E2 (AtUGT74E2), which transfers glucose to indole-3-butyric acid (IBA), is involved in regulating plant architecture and stress responses. Here, we show novel and distinct roles of UGT74E2 in rice. We found that overexpression of AtUGT74E2 in rice could enhance seed germination. This effect was also observed in the presence of IBA and abscisic acid (ABA), as well as salt and drought stresses. Further investigation indicated that the overexpression lines had lower levels of free IBA and ABA compared to wild-type plants. Auxin signaling pathway gene expression such as for OsARF and OsGH3 genes, as well as ABA signaling pathway genes OsABI3 and OsABI5, was substantially downregulated in germinating seeds of UGT74E2 overexpression lines. Consistently, due to reduced IBA and ABA levels, the established seedlings were less tolerant to drought and salt stresses. The regulation of rice seed germination and stress tolerance could be attributed to IBA and ABA level alterations, as well as modulation of the auxin/ABA signaling pathways by UGT74E2. The distinct roles of UGT74E2 in rice implied that complex and different molecular regulation networks exist between Arabidopsis and rice.

19.
J Formos Med Assoc ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33011035

RESUMO

BACKGROUND/PURPOSE: Prescribing of opioids to patients with non-cancer pain is strictly regulated in Taiwan, but tramadol is not included in the regulation on chronic opioid prescribing. This study aims to identify the utilization trend of prescribing tramadol and other opioid analgesics and investigate the influence of government regulation on opioid prescribing in Taiwan. METHODS: This cross-sectional study used the Taiwan National Health Insurance claims database and the cancer registry from 2001 through 2016. The annual number of adult opioid users, opioid utilization (Defined Daily Doses [DDDs]/1000 registrants) and the number of supply days were enumerated for each calendar year and stratified by cancer or non-cancer patients. Descriptive statistics were used to report the trends in utilization for each calendar year. RESULTS: The regulation strictly limited persistent use of opioids for patients with non-cancer pain, of which only a small proportion of fentanyl (20%) and morphine (<2%) users were prescribed with an annual number of supply days greater than 28 days. The annual utilization of morphine (6.4-53.5 vs. 1.1 to 9.6 DDD/1000 registrants) and fentanyl (8.3-37.0 vs. 0.16 to 1.8 DDD/1000 registrants) to patients with cancer was consistently higher than patients without cancer. In contrast to morphine and fentanyl, the utilization of tramadol prescribed to patients without cancer increased 92.2-fold (3.7-341.2 DDD/1000 registrants) from 2002 to 2016. CONCLUSION: The regulation in Taiwan limited the prescribing of selective opioids for patients with non-cancer pain and the substitution of tramadol for other opioids may have safety implications.

20.
J Biol Chem ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33055235

RESUMO

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RQC domain, and an auxiliary element HRDC domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity, and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA- binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA