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Schroeder Vest posted an update 6 months, 3 weeks ago
In c-DMARD users (n = 53), serially monitored levels of serum VEGF, IL-6, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) all decreased in good and moderate responders but not in nonresponders. In b-DMARD users (n = 49), only serum VEGF well represented the treatment response, while CRP nonspecifically decreased irrespective of the treatment outcome. By multivariable analysis, serum ΔVEGF, but not ΔESR or ΔCRP, was an independent factor associated with good and moderate responses to DMARD. In summary, the angiogenic cytokines PlGF and VEGF represent the synovitis severity of RA assessed by US. In patients receiving b-DMARD, serum VEGF may be more valuable than CRP in reflecting the treatment response.An amendment to this paper has been published and can be accessed via a link at the top of the paper.High-grade serous ovarian cancer (HG-SOC)-often referred to as a “silent killer”-is the most lethal gynecological malignancy. The fallopian tube (murine oviduct) and ovarian surface epithelium (OSE) are considered the main candidate tissues of origin of this cancer. However, the relative contribution of each tissue to HG-SOC is not yet clear. Here, we establish organoid-based tumor progression models of HG-SOC from murine oviductal and OSE tissues. We use CRISPR-Cas9 genome editing to introduce mutations into genes commonly found mutated in HG-SOC, such as Trp53, Brca1, Nf1 and Pten. Our results support the dual origin hypothesis of HG-SOC, as we demonstrate that both epithelia can give rise to ovarian tumors with high-grade pathology. However, the mutated oviductal organoids expand much faster in vitro and more readily form malignant tumors upon transplantation. Furthermore, in vitro drug testing reveals distinct lineage-dependent sensitivities to the common drugs used to treat HG-SOC in patients.Background Child eating behaviors are highly heterogeneous and their longitudinal impact on childhood weight is unclear. The objective of this study was to characterize eating behaviors during the first 10 years of life and evaluate associations with BMI at age 11 years. Method Data were parental reports of eating behaviors from 15 months to age 10 years (n = 12,048) and standardized body mass index (zBMI) at age 11 years (n = 4884) from the Avon Longitudinal Study of Parents and Children. Latent class growth analysis was used to derive latent classes of over-, under-, and fussy-eating. Linear regression models for zBMI at 11 years on each set of classes were fitted to assess associations with eating behavior trajectories. Results We identified four classes of overeating; “low stable” (70%), “low transient” (15%), “late increasing” (11%), and “early increasing” (6%). The “early increasing” class was associated with higher zBMI (boys β = 0.83, 95% CI 0.65, 1.02; girls β = 1.1; 0.92, 1.28) compared with “low stable.” Six classes were found for undereating; “low stable” (25%), “low transient” (37%), “low decreasing” (21%), “high transient” (11%), “high decreasing” (4%), and “high stable” (2%). The latter was associated with lower zBMI (boys β = -0.79; -1.15, -0.42; girls β = -0.76; -1.06, -0.45). Six classes were found for fussy eating; “low stable” (23%), “low transient” (15%), “low increasing” (28%), “high decreasing” (14%), “low increasing” (13%), and “high stable” (8%). The “high stable” class was associated with lower zBMI (boys β = -0.49; -0.68-0.30; girls β = -0.35; -0.52, -0.18). Conclusions Early increasing overeating during childhood is associated with higher zBMI at age 11. High persistent levels of undereating and fussy eating are associated with lower zBMI. Longitudinal trajectories of eating behaviors may help identify children potentially at risk of adverse weight outcomes.Objective Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine’s effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). Methods Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. Results At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. FK866 modulator 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. Conclusions In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine’s IL-6 suppressive effects may be beneficial in COVID-19.Epigenomic modifications are instrumental for transcriptional regulation, but comprehensive reference epigenomes remain unexplored in rice. Here, we develop an enhanced chromatin immunoprecipitation (eChIP) approach for plants, and generate genome-wide profiling of five histone modifications and RNA polymerase II occupancy with it. By integrating chromatin accessibility, DNA methylation, and transcriptome datasets, we construct comprehensive epigenome landscapes across various tissues in 20 representative rice varieties. Approximately 81.8% of rice genomes are annotated with different epigenomic properties. Refinement of promoter regions using open chromatin and H3K4me3-marked regions provides insight into transcriptional regulation. We identify extensive enhancer-like promoters with potential enhancer function on transcriptional regulation through chromatin interactions. Active and repressive histone modifications and the predicted enhancers vary largely across tissues, whereas inactive chromatin states are relatively stable.
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