DNA hypermethylation of SFRP2 influences the pathology of rheumatoid arthritis through the canonical Wnt signaling in model rats

Abstract

In this work, the expression of secreted frizzled related protein 2 (SFRP2) in rheumatoid arthritis (RA) model rats and the mechanisms of SFRP2 on the RA pathogenesis were investigated. Data suggested that SFRP2 was significantly down-regulated in RA model rats compared with normal control, and overexpression of SFRP2 suppressed the RA pathogenesis and the canonical Wnt signaling in fibroblast-like synovial cells (FLS) from RA model rats, whereas knockdown of SFRP2 got an opposite observation. Interestingly, 5-azadC treatment up-regulated the SFRP2 expression, inhibited the FLS proliferation, suppressed the expression of IL-6 and IL-8 and the fibronectin production, suggesting that the decreased SFRP2 in RA model rats was due to the DNA methylation. Furthermore, DNMT1 knockdown up-regulated the SFRP2 expression, DNMT1 overexpression inhibited the SFRP2, and the quantitative methylation-specific PCR (qMSP) confirmed that the DNMT1 has direct methylation roles for the SFRP2 promoter, leading to a regulation of FLS proliferation and fibronectin expression in RA model rats. In addition, up-regulated MeCP2 was involved in the SFRP2 regulation and the pathogenesis of RA model rats, and MeCP2 and DNMT1 have synergistic inhibition roles in the SFRP2 expression. Combination of DNMT1 and DNA methylation may be a promising treatment strategy for individuals with RA in which SFRP2 is down-regulated.     

Sleep quality and risk of cancer: findings from the English longitudinal study of aging

Study ObjectiveTo prospectively examine the association between sleep quality and incident cancer risk in the elderly.MethodsA total of 10,036 participants aged ≥50 years free of cancer at baseline from the English Longitudinal Study of Ageing at wave 4 (2008) were included, and followed up until 2016. The primary endpoint was new onset physician-diagnosed cancer. Sleep quality was assessed by four questions regarding the frequency of sleep problems and overall subjective feeling of sleep quality in the last month, with higher score denoting poorer sleep quality. The multivariable Cox regression model was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for incident cancer risk according to sleep quality.ResultsAt 8-year follow-up, a total of 745 (7.4%) participants developed cancer. Compared with good sleep quality at baseline, HR (95% CI) for incident cancer risk was 1.328 (1.061, 1.662) for intermediate quality, 1.586 (1.149, 2.189) for poor quality. Similarly, compared with maintaining good sleep quality in the first 4 years, HR (95% CI) for incident cancer risk was 1.615 (1.208, 2.160) for maintaining intermediate quality and 1.608 (1.043, 2.480) for maintaining poor quality. The exclusion of participants with family history of cancer or abnormal sleep duration yielded consistent results.ConclusionsPoor sleep quality is positively associated with the long-term risk of developing cancer in an elderly cohort. Both medical staffs and the general public should pay more attention to improving sleep hygiene.     

Di-functional luminescent sensors based on Y3+ doped Eu3+ and Tb3+ coordination polymers: fast response and visible detection of Cr3+, Fe3+ ions in aqueous solutions and acetone

With the careful modulation of the relative ratio of Y³⁺/Eu³⁺and Y³⁺/Tb³⁺, two series of bimetallic RE-CPs (Eu_xY_1−x and Tb_xY_1−x) were successfully obtained through the isomorphous substitution method. Interestingly, the introduction of Y³⁺ ions does not change the fluorescence characteristic peak of 1-Eu and 1-Tb, but enhances its fluorescence lifetime and quantum yield. Experimental and theoretical simulation results show the co-doping process changes the intramolecular energy transfer process and reduces the non-radiative transition resulting from concentration quenching. Eu_0.1Y_0.9 and Tb_0.1Y_0.9 with the largest luminescence lifetime were selected as the representative research objects, their potential application for the detection of toxic metal ions and organic molecules was further investigated. Interestingly, Eu_0.1Y_0.9 and Tb_0.1Y_0.9 demonstrate high sensitivity and good selectivity towards Fe³⁺, Cr³⁺ and acetone. Besides, fine fluorescence visibility provides the necessary conditions for the preparation of simple and fast response fluorescent test papers in order to achieve real-time and convenient detection of these toxic materials.

Two series of doped coordination polymers (Eu_xY_1−x and Tb_xY_1−x) through isomorphous substitution method utilizing Y³⁺ in place of partial Eu³⁺/Tb³⁺ were obtained. The doped materials could detect Fe³⁺, Cr³⁺, and acetone selectively and sensitively.     

Temperature-dependent variations in toxicity of diamide insecticides against three lepidopteran insects

The effect of temperature on the toxicities of four diamide insecticides (chlorantraniliprole, cyantraniliprole, flubendiamide, tetraniliprole) against three lepidopteran insects (Helicoverpa armigera, Plutella xylostella, Athetis lepigone) were determined from 15 to 35 °C by exposing third-instar larvae to dip-treated cabbage leaf. The results indicated that increase in temperature led to an increase significantly and regularly in the toxicities of the four diamide insecticides against P. xylostella and H. armigera, but not for A. lepigone. The temperature coefficients (TCs) of the four diamide insecticides increased from 15 to 35 °C. Tetraniliprole for H. armigera (+825.83), chlorantraniliprole for P. xylostella (+315.65) and cyantraniliprole for H. armigera (+225.77) exhibited high positive TCs. For A. lepigone, temperature had a positively weak or no effect on the toxicities of most of the diamide insecticides from 20 to 30 °C, but a higher effect from 30 to 35 °C. In addition, the toxicities of chlorantraniliprole, cyantraniliprole and tetraniliprole all decreased from 15 to 20 °C. This study can guide pest managers in choosing suitable ambient field temperature when spraying diamide insecticides against lepidopteran insects.     

Intranasal delivery of rapid-onset antidepressants: a new trend of treating major depressive disorder

Existing antidepressants seem to have an onset time of several weeks. However, newly found depression-related receptors and pathways may enlighten us to find more rapid-onset antidepressants, in which ketamine is one of the most potential antidepressants. By intranasal administration, drugs can be directly delivered to the brain via olfactory nerve route, which is proved to be suitable for some antidepressants. Well-designed rapid-onset antidepressants are the urgent requirements of the patients with depression. Intranasal administration, as a potential strategy to deliver antidepressants to brain, can improve drug efficacy and largely shorten the onset time. In this article, we sorted out some new formulation approaches in treating depression with different mechanisms and pathways compared with traditional treating strategies, along with new findings in clinical studies, proving that the combination of rapid-onset antidepressants with intranasal delivery will lead a new trend in treating depression.     

药护协同管理在急性心肌梗死患者溶栓治疗中的实践

目的 探讨药护协同管理在急性心肌梗死患者溶栓治疗中的实践效果.方法 将100例急性心肌梗死溶栓治疗的患者按数字随机法分为常规组(n=50)和协同管理组(n=50),常规组按照常规护理,协同管理组在此基础上实施药护协同管理,干预6个月后比较治疗效果.结果 两组入院后明确诊断至开始溶栓时间、冠脉有效灌注率和住院天数比较,协同干预组显著优于常规组,48h内恶性心律失常发生例数协同组显著少于常规组,差异有统计学意义(均P＜0.05).两组患者溶栓治疗后12h、24 h、48 h、7d的LVEF值比较,差异有统计学意义(均P＜0.05);出院后6个月心脏不良事件发生比例比较,差异无统计学意义(P＞0.05).结论 药护协同管理能够有效缩短急性心肌梗死患者入院后至溶栓的时间,提高冠脉有效灌注,减少48 h内恶性心律失常发生和缩短住院天数,促进心功能恢复.     

Inducible proteins binding to the murine thymidine kinase promoter in late G1/S phase.

By performing DNase I footprint and band-shift analyses of a 170-base-pair region of the murine thymidine kinase promoter, we identified an inducible DNA binding activity that we named Yi. Yi binding activity was not detected in G0 and G1 extracts, but it was observed as cells crossed the G1/S boundary. Yi proteins bind specifically to a consensus sequence (CCCNCNNNCT) found at three distinct sites in this promoter region. We also observed a murine Sp1 binding activity that was constitutive throughout the cell cycle. We propose that the G1/S-specific Yi binding is important for murine thymidine kinase gene regulation and perhaps also for initiation of DNA synthesis.     

Molecular Analysis of Codon 548 in the rpoB Gene Involved in Mycobacterium tuberculosis Resistance to Rifampin

Most Mycobacterium tuberculosis rifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance-determining region (RRDR) in the gene rpoB. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinant Mycobacterium smegmatis and M. tuberculosis isolates carrying mutated rpoB (Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of the rpoB gene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.