Egholmsheehan1517

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3, VitD3) is the major active ingredient of vitamin D and has anti-inflammatory activity; however, the mechanism for this remains poorly understood. In this study, we found that VitD3 was able to abolish NOD-like receptor protein 3 (NLRP3) inflammasome activation and subsequently inhibit caspase-1 activation and IL-1β secretion via the vitamin D receptor (VDR). Furthermore, VitD3 specifically prevented NLRP3-mediated apoptosis-associated speck-like protein with a caspase-recruitment domain (ASC) oligomerization. In additional to this, NLRP3 binding to NIMA-related kinase 7 (NEK7) was also inhibited. Notably, VitD3 inhibited autophagy, leading to the inhibition of the NLRP3 inflammasome. Uncoupling protein 2-reactive oxygen species signaling may be involved in inflammasome suppression by VitD3. Importantly, VitD3 had both preventive and therapeutic effects on mouse model of ulcerative colitis, via inhibition of NLRP3 inflammasome activation. Our results reveal a mechanism through which VitD3 represses inflammation and prevents the relevant diseases, and suggest a potential clinical use of VitD3 in autoimmune syndromes or other NLRP3 inflammasome-driven inflammatory diseases. ©2020 Society for Leukocyte Biology.BACKGROUND The importance of capturing and reporting health-related quality of life (HRQOL) in clinical trials has been increasingly recognized in the oncology field. As a result, the National Cancer Institute (NCI) began to provide support for correlative HRQOL studies in cancer treatment trials. The current study was conducted to assess the publication rate of HRQOL correlative studies in NCI-supported treatment trials and to identify potential factors positively or negatively associated with publication rates. METHODS The NCI conducted a retrospective review of existing NCI databases to identify cancer treatment trials that had obtained additional NCI funding for the assessment of HRQOL and to determine the extent to which funded HRQOL studies have been completed and published in a peer-reviewed journal. RESULTS Of the 108 included trials, 58 (54%) had a parent trial (PT) publication; of these, 36 trials (62%) had a published HRQOL result 20 as an independent publication and 16 that were included and/or reported in the PT publication. The length of time between trial activation and closure, as well as the specific cancer, appeared to be associated with the publication rates. CONCLUSIONS The results of the current study demonstrated that approximately 45% of the PT publications were followed by a HRQOL publication within 1 year, to allow the knowledge to be used in patient treatment decision making. The authors believe the current analysis is an important first step toward a better understand of the challenges that researchers face when reporting HRQOL endpoints. © 2020 American Cancer Society.KEY POINTS Spinal cord dorsal horn srGAP3 increases in the initiation phase of neuropathic pain and decreases in the maintenance phase. However, Rac1 activity which can be reduced by srGAP3, decreased in the initiation phase and increased in the maintenance phase. The increased srGAP3 in the initiation phase promotes new immature dendritic spines instigating neuropathic pain. Decreased srGAP3 in the maintenance phase enhances Rac1 activity facilitating maturation of dendritic spines and the persistence of neuropathic pain. srGAP3 siRNA can ameliorate neuropathic pain only when administrated in the initiation phase. The Rac1 inhibitor can ameliorate neuropathic pain only when administrated in the maintenance phase. Combined targeting of srGAP3 in the initiation phase and Rac1 in the maintenance phase can produce optimal analgesic efficacy. ABSTRACT Neuropathic pain includes an initiation phase and maintenance phase, each with different pathophysiological processes. Understanding the synaptic plasticity and molegies for different phases of neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Information on the genetic architecture of phenotypic traits is helpful for constructing and testing models of the eco-evolutionary dynamics of natural populations. For plant groups with long life cycles there is a lack of line cross experiments that can unravel the genetic architecture of loci underlying quantitative traits. To fill this gap, we propose the use of variation for phenotypic traits expressed in natural hybrid zones as an alternative approach. We used data from orchid hybrid zones and compared expected and observed patterns of phenotypic trait expression in different early generation hybrid classes identified by molecular genetic markers. OTS964 We found evidence of additivity, dominance, and epistatic interactions for different phenotypic traits. We discuss the potential of this approach along with its limitations and suggest it may represent a realistic way to gain an initial insight into the heritability and genomic architecture of traits in organismal groups with complex life history, such as orchids and many others. This article is protected by copyright. All rights reserved.Molecular targeted therapies against EGFR and ALK have improved the quality of life of lung adenocarcinoma patients. However, targetable driver mutations are mainly found in TTF-1/NKX2-1-positive terminal respiratory unit (TRU) types and rarely in non-TRU types. To elucidate the molecular characteristics of the major subtypes of non-TRU-type adenocarcinomas, we analyzed 19 lung adenocarcinoma cell lines (11 TRU types and 8 non-TRU types). A characteristic of non-TRU-type cell lines was the strong expression of TFF-1 (trefoil factor-1), a gastric mucosal protective factor. An immunohistochemical analysis of 238 primary lung adenocarcinomas resected at Jichi Medical University Hospital revealed that TFF-1 was positive in 31 cases (13%). TFF-1 expression was frequently detected in invasive mucinous(14/15,93%), enteric(2/2,100%), and colloid(1/1,100%) adenocarcinomas, less frequent in acinar(5/24,21%), papillary(7/120,6%), and solid(2/43,5%) adenocarcinomas, and negative in micropapillary(0/1,0%), lepidic(0/23,0%), and microinvasive adenocarcinomas or adenocarcinoma in situ(0/9,0%).