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Seung Min Jung, Jaeseon Lee, Seung Ye Baek, Juhyun Lee, Se Gwang Jang, Seung-Min Hong, Jin-Sil Park, Mi-La Cho, Sung-Hwan Park, Seung-Ki Kwok
This study aimed to evaluate the therapeutic effect of fraxinellone on inflammatory arthritis and identify the underlying mechanisms. Fraxinellone (7.5 mg/kg) or a vehicle control was injected into mice with collagen-induced arthritis (CIA). The severity of arthritis was evaluated clinically and histologically. The differentiation of CD4⁺ T cells and CD19⁺ B cells was investigated in the presence of fraxinellone. Osteoclastogenesis after fraxinellone treatment was evaluated by staining with tartrate-resistant acid phosphatase (TRAP) and by measuring the mRNA levels of osteoclastogenesis-related genes...
March 13, 2018: International Journal of Molecular Sciences
Suchi Srivastava, Sonal Srivastava, Vidisha Bist, Surabhi Awasthi, Reshu Chauhan, Vasvi Chaudhry, Poonam C Singh, Sanjay Dwivedi, Abhishek Niranjan, Lalit Agrawal, Puneet Singh Chauhan, Rudra Deo Tripathi, Chandra Shekhar Nautiyal
Rice grown in arsenic (As) contaminated areas contributes to high dietary exposure of As inducing multiple adverse effects on human health. The As contamination and application of phosphate fertilizers during seedling stage creates a high P and As stress condition. The flooded paddy fields are also conducive for algal growth and microbial activity. The present study proposes potential role of microalgae, Chlorella vulgaris (CHL) and bacteria, Pseudomonas putida (RAR) on rice plant grown under excess As and phosphate (P) conditions...
February 23, 2018: Journal of Hazardous Materials
Constance A Mitchell, Subham Dasgupta, Sharon Zhang, Heather M Stapleton, David C Volz
Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on 1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and 2) high-content screening to identify nuclear receptor ligands that enhance or mitigate TPHP-induced cardiotoxicity. Based on mRNA-sequencing, TPHP exposure from 24 to 72 h post fertilization (hpf) resulted in a concentration-dependent increase in the number of transcripts significantly affected at 72 hpf, and pathway analysis revealed that five out of nine nuclear receptor pathways were associated with the retinoid X receptor (RXR)...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Maryam Majd, Aref Hosseini, Kamran Ghaedi, Abbas Kiani-Esfahani, Somayeh Tanhaei, Hanieh Shiralian-Esfahani, Seyed Yahya Rahnamaee, Seyed Javad Mowla, Mohammad Hossein Nasr-Esfahani
Objectives: Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS. Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiation, the role of microRNAs in MS is not completely understood. Thereby, as a step closer, we analyzed the expression profile of miR-9-5p and miR-106a-5p, and protein level of retinoic acid receptor (RAR)-related orphan receptor C ( RORC ; Th17 master transcription factor) as direct target of miR-106a-5p and forkhead box P3 ( FOXP3 ; Treg master transcription factor) as indirect target of miR-9-5p in CD4+ T cells in two groups of relapsing and remitting in our relapsing-remitting MS (RR-MS) patients...
March 2018: Iranian Journal of Basic Medical Sciences
Chang H Kim
Lymphocytes, such as T cells, B cells, and innate lymphoid cells (ILCs), play central roles in regulating immune responses. Retinoic acids (RAs) are vitamin A metabolites, produced and metabolized by certain tissue cells and myeloid cells in a tissue-specific manner. It has been established that RAs induce gut-homing receptors on T cells, B cells, and ILCs. A mounting body of evidence indicates that RAs exert far-reaching effects on functional differentiation and fate of these lymphocytes. For example, RAs promote effector T cell maintenance, generation of induced gut-homing regulatory and effector T cell subsets, antibody production by B cells, and functional maturation of ILCs...
February 2018: Immune Network
Mette Handberg-Thorsager, Juliana Gutierrez-Mazariegos, Stefan T Arold, Eswar Kumar Nadendla, Paola Y Bertucci, Pierre Germain, Pavel Tomançak, Keely Pierzchalski, Jace W Jones, Ricard Albalat, Maureen A Kane, William Bourguet, Vincent Laudet, Detlev Arendt, Michael Schubert
Retinoic acid (RA) is an important intercellular signaling molecule in vertebrate development, with a well-established role in the regulation of hox genes during hindbrain patterning and in neurogenesis. However, the evolutionary origin of the RA signaling pathway remains elusive. To elucidate the evolution of the RA signaling system, we characterized RA metabolism and signaling in the marine annelid Platynereis dumerilii , a powerful model for evolution, development, and neurobiology. Binding assays and crystal structure analyses show that the annelid retinoic acid receptor (RAR) binds RA and activates transcription just as vertebrate RARs, yet with a different ligand-binding pocket and lower binding affinity, suggesting a permissive rather than instructive role of RA signaling...
February 2018: Science Advances
Farjam Goudarzi, Adel Mohammadalipour, Iraj Khodadadi, Sheno Karimi, Rezvan Mostoli, Majid Bahabadi, Mohammad Taghi Goodarzi
Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca2+ play important roles in different stages of this process. Because of the complicated roles of Ca2+ in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca2+ into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca2+ or 1.8 mM Ca2+ plus calcium ionophore, A23187, for 3 days...
February 27, 2018: Molecular Biotechnology
Marine Lacomme, François Medevielle, Henri-Marc Bourbon, Elodie Thierion, Dirk-Jan Kleinjan, Mélanie Roussat, Fabienne Pituello, Sophie Bel-Vialar
Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known...
February 24, 2018: Developmental Biology
Chaninya Wongwarangkana, Nasamon Wanlapakorn, Jira Chansaenroj, Yong Poovorawan
Cervical cancer is one of the leading causes of death in women worldwide, particularly in developing countries. Human papillomavirus has been reported as one of the key etiologic factors in cervical carcinoma. Likewise, epigenetic aberrations have ability to regulate cancer pathogenesis and progression. Recent research suggested that methylation has been detected already at precancerous stages, which methylation markers may have significant value in cervical cancer screening. The retinoic acid receptor beta ( RAR β) gene, a potential tumor suppressor gene, is usually expressed in normal epithelial tissue...
February 12, 2018: World Journal of Virology
Haoran Ji, Dongxiao Li, Ye Wu, Quanli Zhang, Qiang Gu, Han Xie, Taoyun Ji, Huifang Wang, Lu Zhao, Haijuan Zhao, Yanling Yang, Hongchun Feng, Hui Xiong, Jinhua Ji, Zhixian Yang, Liping Kou, Ming Li, Xinhua Bao, Xingzhi Chang, Yuehua Zhang, Li Li, Huijuan Li, Zhengping Niu, Xiru Wu, Jiangxi Xiao, Yuwu Jiang, Jingmin Wang
OBJECTIVE: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population. METHODS: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing...
2018: PloS One
Dongkai Guo, Shun Zhang, Hongyang Sun, Xingyun Xu, Zongbing Hao, Chenchen Mu, Xingshun Xu, Guanghui Wang, Haigang Ren
Abelson helper integration site 1 (AHI1) is associated with several neuropsychiatric and brain developmental disorders such as schizophrenia, depression, autism, and Joubert syndrome. Ahi1 deficiency in mice leads to behaviors typical of depression. However, the mechanisms by which AHI1 regulates behavior remain to be elucidated. Here, we found that down-regulation of expression of the rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase (TH), in the midbrains of Ahi1 -knockout (KO) mice is responsible for Ahi1 -deficiency-mediated depressive symptoms...
February 15, 2018: Journal of Biological Chemistry
Ignacio Miro Estruch, Laura H J de Haan, Diana Melchers, René Houtman, Jochem Louisse, John P Groten, Ivonne M C M Rietjens
Estrogen receptor alpha (ERα) and retinoic acid receptors (RARs) play important and opposite roles in breast cancer growth. While exposure to ERα agonists such as 17β-estradiol (E2 ) is related to proliferation, RAR agonists such as all-trans retinoic acid (AtRA) induce anti-proliferative effects. Although crosstalk between these pathways has been proposed, the molecular mechanisms underlying this interplay are still not completely unraveled. The aim of this study was to evaluate the effects of AtRA on ERα-mediated signaling in the ERα positive cell lines MCF7/BUS and U2OS-ERα-Luc to investigate some of the possible underlying modes of action...
February 15, 2018: Journal of Receptor and Signal Transduction Research
Hesham Haffez, David R Chisholm, Natalie J Tatum, Roy Valentine, Christopher Redfern, Ehmke Pohl, Andrew Whiting, Stefan Przyborski
Retinoids, such as all-trans-retinoic acid (ATRA), regulate cellular differentiation and signalling pathways in chordates by binding to nuclear retinoic acid receptors (RARα/β/γ). Polar interactions between receptor and ligand are important for binding and facilitating the non-polar interactions and conformational changes necessary for RAR-mediated transcriptional regulation. The constraints on activity and RAR-type specificity with respect to the structural link between the polar and non-polar functions of synthetic retinoids are poorly understood...
February 10, 2018: Bioorganic & Medicinal Chemistry
Yumin Huang, John Hale, Yaomei Wang, Wei Li, Shijie Zhang, Jieying Zhang, Huizhi Zhao, Xinhua Guo, Jing Liu, Hongxia Yan, Karina Yazdanbakhsh, Gang Huang, Christopher D Hillyer, Narla Mohandas, Lixiang Chen, Ling Sun, Xiuli An
BACKGROUND: SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown. METHODS: shRNA-mediated approach was used to knockdown SF3B1 in human CD34+ cells...
February 12, 2018: Journal of Hematology & Oncology
Abu Sadat Md Sayem, Nelli Giribabu, Kamarulzaman Karim, Lay Khiang Si, Sekaran Muniandy, Naguib Salleh
Sex-steroids play important role in modulating uterine functions. We hypothesized that these hormones affect expression of proteins in the uterus related to thyroid hormone action. Therefore, changes in expression levels of receptors for thyroid hormone (TRα-1 and TRβ-1), thyroid stimulating hormone (TSHR), vitamin D (VDR) and retinoid acid (RAR) as well as extracellular signal-regulated kinase (ERK1/2) in uterus were investigated under sex-steroid influence. METHODS: Two rat models were used: (i) ovariectomised, sex-steroid replaced and (ii) intact, at different phases of oestrous cycle...
February 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jorge Viera-Vera, José E García-Arrarás
Retinoic acid receptors (RAR) and retinoid X receptors (RXR) are ligand-mediated transcription factors that synchronize intricate signaling networks in metazoans. Dimer formation between these two nuclear receptors mediates the recruitment of co-regulatory complexes coordinating the progression of signaling cascades during developmental and regenerative events. In the present study we identified and characterized the receptors for retinoic acid in the sea cucumber Holothuria glaberrima; a model system capable of regenerative organogenesis during adulthood...
February 6, 2018: Gene
Xiaolong Wang, Qiling Zhang, Zhe Zhou, Manjiao Liu, Yubao Chen, Jianbo Li, Linlin Xu, Jing Guo, Qingjun Li, Jing Yang, Shengqi Wang
Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus-host interactions, and several key host molecules involved in the HAdV infection process were identified...
February 5, 2018: Antiviral Research
Shigeharu Ueki, Junko Nishikawa, Mineyo Fukuchi, Yasunori Konno, Masahide Takeda, Yuki Moritoki, Junichi Chihara, Ayumi Omokawa, Tomoo Saga, Makoto Hirokawa
Active metabolites of vitamin A, retinoic acids (RAs), are known to play critical roles in mucosal immune responses and dramatically inhibit human eosinophil apoptosis, but the detailed mechanisms have not been elucidated. We previously screened for ICAM-1 (CD54) upregulation in RA-stimulated human eosinophils by gene microarray analysis. As ICAM-1 induction and activation were observed to have a role in maintenance of eosinophil survival, we tested the hypothesis that RAs prolong eosinophil survival through ICAM-1 outside-in signaling...
January 31, 2018: Immunology Letters
Qiang Zhao, Ke Wu, Nannan Li, Zhengmei Li, Fenglin Jin
Myocardial infarction (MI) is a heart disease with high morbidity and mortality rates, thus it is critical to identify genes that serve roles during its pathogenesis. The objective of the present study was to identify potentially relevant genes during the progression of the disease. Blood samples from patients with MI and normal controls (n=3/group) were obtained, the RNA was extracted and cDNA libraries were established. RNA sequencing (RNA-seq) was performed on a HiSeq 2500 platform and fragments per kilobase of exon per million fragments mapped was utilized to calculate the gene expression value following preprocessing of the RNA-seq data...
February 2018: Experimental and Therapeutic Medicine
B Li, J Y Wang, J Q Liu, Z X Shi, S L Peng, H J Huang, T J Qin, Z F Xu, Y Zhang, L W Fang, H L Zhang, N B Hu, L J Pan, S Q Qu, Z J Xiao
Objective: To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients. Methods: A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed. Results: Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) ...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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