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https://www.readbyqxmd.com/read/28724938/a-novel-role-for-rar%C3%AE-agonists-as-apolipoprotein-ciii-inhibitors-identified-from-high-throughput-screening
#1
Sang Jun Lee, Madhupriya Mahankali, Abdallah Bitar, Huafei Zou, Elizabeth Chao, Hung Nguyen, Jose Gonzalez, Dawna Caballero, Mitch Hull, Danling Wang, Peter G Schultz, Weijun Shen
Elevated triglyceride (TG) levels are well-correlated with the risk for cardiovascular disease (CVD). Apolipoprotein CIII (ApoC-III) is a key regulator of plasma TG levels through regulation of lipolysis and lipid synthesis. To identify novel regulators of TG levels, we carried out a high throughput screen (HTS) using an ApoC-III homogenous time resolved fluorescence (HTRF) assay. We identified several retinoic acid receptor (RAR) agonists that reduced secreted ApoC-III levels in human hepatic cell lines. The RARα specific agonist AM580 inhibited secreted ApoC-III by >80% in Hep3B cells with an EC50 ~2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723671/qishenyiqi-pill-attenuates-atherosclerosis-by-promoting-regulatory-t-cells-inhibiting-t-helper-17-cells-and-accelerating-cholesterol-excretion
#2
Li Peng, Chong-Shan Lv, Yun Zhao, Shao-Dong Chen, Yang Huang, Da-Wei Lu, Shu-Qiong Huang, Zong-Bao Yang, Lin-Chao Qian, Lei Wen
OBJECTIVE: The aim of this study was to explore potential immunoregulatory mechanisms underlying the suppressive effect on atherosclerosis of QiShenYiQi pill (QSYQ). METHODS AND RESULTS: Male ApoE-/- mice were maintained on a Western-type diet and QSYQ treatment for eight weeks. Determination of atherosclerosis demonstrated that QSYQ attenuated plaque formation and decreased the level of blood low-density lipoproteins-cholesterol. QSYQ treatment did not affect body weight but reduced the ratio of liver weight and body weight...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723518/mid-term-outcomes-following-salvage-lymph-node-dissection-for-prostate-cancer-nodal-recurrence-status-post-radical-prostatectomy
#3
Fabio Zattoni, Avinash Nehra, Christopher R Murphy, Laureano Rangel, Lance Mynderse, Val Lowe, Eugene Kwon, R Jeffrey Karnes
BACKGROUND: Patients with oligometastatic prostate cancer lymph node recurrence can be treated with many options including salvage lymph node dissection (sLND). OBJECTIVE: Evaluation of outcomes of sLND and identification of clinicopathologic features in predicting further biochemical and radiological relapse after sLND for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Between November 1, 2009 and March 31, 2015, 117 patients with biochemical recurrence (BCR) after radical prostatectomy (RP) underwent sLND by a single surgeon after a standardized 11C-choline positron emission tomography/computed tomography...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28715808/retinoic-acid-facilitates-toll-like-receptor-4-expression-to-improve-intestinal-barrier-function-through-retinoic-acid-receptor-beta
#4
Yingying Li, Yuan Gao, Ting Cui, Ting Yang, Lan Liu, Tingyu Li, Jie Chen
BACKGROUND/AIMS: Vitamin A (VA) protects the intestinal epithelial barrier by improving cell migration and proliferation. Our previous studies demonstrated that VA deficiency (VAD) during pregnancy suppresses the systemic and mucosal immune responses in the intestines of offspring and that VA supplementation (VAS) during early life can increase immune cell counts. However, little is known about the mechanisms by which VA regulates intestinal epithelial barrier function. METHODS: Caco-2 cells were treated with all-trans retinoic acid (ATRA) for 24 hours to determine the optimum ATRA concentration to which the cells in question respond...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28713967/involvement-of-notch2-in-all%C3%A2-trans-retinoic-acid%C3%A2-induced-inhibition-of-mouse-embryonic-palate-mesenchymal-cell-proliferation
#5
Yadong Zhang, Shiyi Dong, Jianning Wang, Miao Wang, Mu Chen, Hongzhang Huang
Cleft palate is among the most common congenital disorders, and can be induced by exposure to all‑trans retinoic acid (atRA) during mice and human embryogenesis. However, the mechanism underlying the implication of atRA in the development of cleft palate has yet to be elucidated. In the present study, atRA administered by gavage resulted in formation of a cleft palate in 99% of treated C57BL/6 mice. Notch2 was revealed to be upregulated in mouse embryonic palate mesenchymal (MEPM) cells in the atRA‑treated group compared with untreated control mice between embryonic day (E)12...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710010/local-network-component-analysis-for-quantifying-transcription-factor-activities
#6
Qianqian Shi, Chuanchao Zhang, Weifeng Guo, Tao Zeng, Lina Lu, Zhonglin Jiang, Ziming Wang, Juan Liu, Luonan Chen
Transcription factors (TFs) could regulate physiological transitions or determine stable phenotypic diversity. The accurate estimation on TF regulatory signals or functional activities is of great significance to guide biological experiments or elucidate molecular mechanisms, but still remains challenging. Traditional methods identify TF regulatory signals at the population level, which masks heterogeneous regulation mechanisms in individuals or subgroups, thus resulting in inaccurate analyses. Here, we propose a novel computational framework, namely Local Network Component Analysis (LNCA), to exploit data heterogeneity and automatically quantify accurate transcription factor activity (TFA) in practical terms, through integrating the partitioned expression sets (i...
July 11, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28704638/regulator-of-calcineurin-3-ameliorates-autoimmune-arthritis-by-suppressing-th17-cell-differentiation
#7
Jin-Sil Park, Jeong-Hee Jeong, Jae-Kyeong Byun, Mi-Ae Lim, Eun-Kyung Kim, Sung-Min Kim, Si-Young Choi, Sung-Hwan Park, Jun-Ki Min, Mi-La Cho
Regulator of calcineurin 3 (RCAN3), an endogenous regulator of the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, inhibits the phosphatase activity of calcineurin, the nuclear translocation of NFAT, and the NFAT downstream pathway. To investigate the effects of RCAN3 on T-cell regulatory function and the development and progression of inflammatory arthritis, we studied the effects of RCAN3 transfection on regulation of Th17 cell differentiation in a murine T-lymphoma cell line and primary splenic CD4(+) T cells...
July 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28694088/enhanced-expression-of-tumour-suppressor-rar-%C3%AE-by-dspc-nano-formulated-lipo-atra-in-the-lung-of-b16f10-cell-implanted-c57bl6-mice-and-in-a549-cells
#8
V M Berlin Grace, Reshma Mahima Reji, Viswanathan Sundaram
AIM: All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular therapeutic effect on lung cancer. The objective was to find whether it could enhance ATRA receptor, RAR-β expression in lung cells as it was lost in majority of cancers including lung cancer. MATERIALS AND METHODS: The study was made in an experimental C57BL/6 mice model developed by tail vein injection of B16F10 cells and in A549 human lung cancer cells...
July 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28693206/role-of-t-helper-17-cytokines-in-the-tumour-immune-inflammation-response-of-patients-with-laryngeal-squamous-cell-carcinoma
#9
Wei-Jing Tang, Lei Tao, Li-Ming Lu, Di Tang, Xiao-Lin Shi
Altered cytokine production can lead to immune dysfunction in patients with cancer. The present study investigated the expression of T helper (Th)17 cytokines in patients with laryngeal squamous cell carcinoma (LSCC) and their clinical significance in providing new therapeutic insights. The prevalence of Th17 cells and their receptors in patients with LSCC was studied using immunohistochemical analysis via tissue microarray technology. Flow cytometry was used to investigate the percentage of Th17 and Th1 cells in peripheral blood mononuclear cells...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692043/cross-talk-between-progesterone-receptors-and-retinoic-acid-receptors-in-regulation-of-cytokeratin-5-positive-breast-cancer-cells
#10
L M Fettig, O McGinn, J Finlay-Schultz, D V LaBarbera, S K Nordeen, C A Sartorius
Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. We and others have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. We previously discovered that retinoids block P4 induction of CK5+ cells. Here we investigated the mechanisms by which progesterone receptors (PR) and retinoic acid receptors (RAR) regulate CK5 expression and breast CSC activity...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28689802/comparison-of-phenotypic-and-global-gene-expression-changes-in-xenopus-tropicalis-embryos-induced-by-agonists-of-rar-and-rxr
#11
Jingmin Zhu, Lingling Hu, Lingyun Li, Xiao Huang, Huahong Shi
Retinoic acid functions through two classes of receptors, i.e., the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The difference in the role between RAR and RXR, however, are not well clarified. In the present study, we comparatively investigated the phenotypic and global gene expression changes in Xenopus tropicalis embryos induced by three different agonists, including a RAR selective ligand (all-trans retinoic acid, at-RA), a RXR selective ligand (fluorobexarotene, FBA) and their common ligand (9-cis retinoic acid, 9c-RA)...
July 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28675080/radiodensity-of-the-ostiomeatal-complex-in-recurrent-acute-rhinosinusitis
#12
Sean M Johnson, Adam L Honeybrook, Vaibhav H Ramprasad, Ralph Abi Hachem, David W Jang
Objective Recurrent acute rhinosinusitis (RARS) can be an elusive diagnosis due to the lack of clinical and radiographic findings in between acute episodes. This study aims to identify objective computed tomography (CT) characteristics in RARS. Study Design Case series with chart review. Setting Tertiary academic medical center. Subjects and Methods Patients meeting diagnostic criteria for RARS were identified retrospectively from the senior author's practice. Patients were diagnosed with RARS if they experienced 3 or more episodes of acute sinusitis within the past year with complete resolution of symptoms in between episodes...
June 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28669525/mechanisms-of-skin-toxicity-associated-with-metabotropic-glutamate-receptor-5-negative-allosteric-modulators
#13
Falgun Shah, Antonia F Stepan, Alison O'Mahony, Sharlene Velichko, Alexandra E Folias, Christopher Houle, Christopher L Shaffer, John Marcek, Jessica Whritenour, Robert Stanton, Ellen L Berg
Cutaneous reactions represent one of the most common adverse drug effects observed in clinical trials leading to substantial compound attrition. Three negative allosteric modulators (NAMs) of metabotropic glutamate receptors (mGluRs), which represent an important target for neurological diseases, developed by Pfizer, were recently failed in preclinical development due to delayed type IV skin hypersensitivity observed in non-human primates (NHPs). Here we employed large-scale phenotypic profiling in standardized panels of human primary cell/co-culture systems to characterize the skin toxicity mechanism(s) of mGluR5 NAMs from two different series...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28668836/microrna-profiling-and-target-genes-related-to-metastasis-of-salivary-adenoid-cystic-carcinoma
#14
Xin Feng, Kyle Matsuo, Tan Zhang, Yunping Hu, Ashley C Mays, James D Browne, Xiaobo Zhou, Christopher A Sullivan
BACKGROUND/AIM: Perineural invasion and distant metastasis lead to a poor prognosis of adenoid cystic carcinoma and there is no effective therapy available. MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression, which can be biomarkers or therapeutic targets for certain cancer types. We aimed to identify miRNAs and their target genes possibly involved in metastasis of salivary gland adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Using Nanostring nCounter analysis, we examined miRNA expression in two SACC cell lines: SACC-83 and SACC-LM, with low and high lung metastasis rates, respectively...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28659824/hypersensitivity-of-vagal-pulmonary-afferents-induced-by-tumor-necrosis-factor-alpha-in-mice
#15
Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee
Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28656058/melatonin-suppresses-neuropathic-pain-via-mt2-dependent-and-independent-pathways-in-dorsal-root-ganglia-neurons-of-mice
#16
Jia-Ji Lin, Ye Lin, Tian-Zhi Zhao, Chun-Kui Zhang, Ting Zhang, Xiao-Li Chen, Jia-Qi Ding, Ting Chang, Zhuo Zhang, Chao Sun, Dai-Di Zhao, Jun-Lin Zhu, Zhu-Yi Li, Jin-Lian Li
Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation...
2017: Theranostics
https://www.readbyqxmd.com/read/28642153/characterization-of-the-differential-coregulator-binding-signatures-of-the-retinoic-acid-receptor-subtypes-upon-ant-agonist-action
#17
Ignacio Miro Estruch, Diana Melchers, René Houtman, Laura H J de Haan, John P Groten, Jochem Louisse, Ivonne M C M Rietjens
Retinoic Acid Receptor alpha (RARα/NR1B1), Retinoic Acid Receptor beta (RARβ/NR1B2) and Retinoic Acid Receptor gamma (RARγ/NR1B3) are transcription factors regulating gene expression in response to retinoids. Within the RAR genomic pathways, binding of RARs to coregulators is a key intermediate regulatory phase. However, ligand-dependent interactions between the wide variety of coregulators that may be present in a cell and the different RAR subtypes are largely unknown. The aim of this study is to characterize the coregulator binding profiles of RARs in the presence of the pan-agonist all-trans-Retinoic Acid (AtRA); the subtype-selective agonists Am80 (RARα), CD2314 (RARβ) and BMS961 (RARγ); and the antagonist Ro415253...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28635660/diverse-regulation-of-vitamin-d-receptor-gene-expression-by-1-25-dihydroxyvitamin-d-and-atra-in-murine-and-human-blood-cells-at-early-stages-of-their-differentiation
#18
Sylwia Janik, Urszula Nowak, Agnieszka Łaszkiewicz, Anastasiia Satyr, Michał Majkowski, Aleksandra Marchwicka, Łukasz Śnieżewski, Klaudia Berkowska, Marian Gabryś, Małgorzata Cebrat, Ewa Marcinkowska
Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, as the fusion of RARα gene with PML gene initiates acute promyelocytic leukemia where differentiation of the myeloid lineage is blocked, followed by an uncontrolled proliferation of leukemic blasts. RARα takes part in regulation of VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28627588/il%C3%A2-22-expression-is-increased-variedly-in-the-initial-phase-onset-and-chronic-phase-of-a-pristane%C3%A2-induced-arthritis-rat-model
#19
Weikun Hou, Bo Wang, Yan Zhou, Ke Xu, Liesu Meng, Wenhua Zhu, Congshan Jiang, Peng Xu, Shemin Lu
The aim of the present study was to investigate the expression pattern of T helper (Th) 17 and Th22 cell-related factors in a pristane‑induced arthritis (PIA) rat model. PIA rats were divided into the initial phase group [day (D) 6 post‑pristane injection], the onset of clinical arthritis group (D12), the acute arthritis group (D26) and the chronic arthritis group (D70). Rats injected with saline alone were used as the control group. The mRNA expression levels of interleukin (IL)‑17A, IL‑17F, interferon (IFN)‑γ, IL‑22, IL‑22 receptor (R) 1, IL‑22 binding protein (BP) and RAR‑related orphan receptor α were examined in the spleen and/or synovium of the various phases of PIA rats by reverse transcription‑quantitative polymerase chain reaction analysis...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28614782/macrophages-are-targets-of-retinoic-acid-signaling-during-the-wound-healing-process-after-thulium-laser-resection-of-the-prostate
#20
Dian-Jun Yu, Xing-Jie Wang, Yun-Feng Shi, Chen-Yi Jiang, Rui-Zhe Zhao, Yi-Ping Zhu, Li Chen, Yuan-Qing Yang, Xiao-Wen Sun, Shu-Jie Xia
BACKGROUND: The wound-healing process is very important for reducing complications after thulium laser resection of the prostate (TmLRP). The retinoic acid (RA) signaling pathway has been well studied in the wound-healing process of the skin and other organs. The goals of this study were to identify the role of RA signaling in the repair of the prostate after TmLRP and to investigate the molecular mechanism of this process. RESULTS: Retinoic acid receptors (RARs) were present in the prostate, and their expression was increased after TmLRP...
May 26, 2017: Oncotarget
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