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https://www.readbyqxmd.com/read/28229025/effect-of-interleukin-il-35-on-il-17-expression-and-production-by-human-cd4-%C3%A2-t-cells
#1
Kosuke Okada, Takeki Fujimura, Takeshi Kikuchi, Makoto Aino, Yosuke Kamiya, Ario Izawa, Yuki Iwamura, Hisashi Goto, Iichiro Okabe, Eriko Miyake, Yoshiaki Hasegawa, Makio Mogi, Akio Mitani
BACKGROUND: Interleukin (IL)-17 produced by mainly T helper 17 (Th17) cells may play an important destructive role in chronic periodontitis (CP). Thus, anti-inflammatory cytokines, such as IL-35, might have a beneficial effect in periodontitis by inhibiting differentiation of Th17 cells. Th17 differentiation is regulated by the retinoic acid receptor-related orphan receptor (ROR) α (encoded by RORA) and RORγt (encoded by RORC). However, the role of IL-35 in periodontitis is not clear and the effect of IL-35 on the function of Th17 cells is still incompletely understood...
2017: PeerJ
https://www.readbyqxmd.com/read/28177907/genetic-variation-of-clock-genes-and-cancer-risk-a-field-synopsis-and-meta-analysis
#2
Clara Benna, Charlotte Helfrich-Förster, Senthilkumar Rajendran, Halenya Monticelli, Pierluigi Pilati, Donato Nitti, Simone Mocellin
BACKGROUND: The number of studies on the association between clock genes' polymorphisms and cancer susceptibility has increased over the last years but the results are often conflicting and no comprehensive overview and quantitative summary of the evidence in this field is available. RESULTS: Literature search identified 27 eligible studies comprising 96756 subjects (cases: 38231) and investigating 687 polymorphisms involving 14 clock genes. Overall, 1025 primary and subgroup meta-analyses on 366 gene variants were performed...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28130419/the-retinoic-acid-receptor-related-orphan-receptor-%C3%AE-positively-regulates-tight-junction-protein-claudin-domain-containing-1-mrna-expression-in-human-brain-endothelial-cells
#3
Hiroshi Matsuoka, Akiho Shima, Arisa Uda, Hirotaka Ezaki, Akihiro Michihara
Members of the claudin family play important roles in the formation of tight junctions (TJs) in several tissues. Claudin domain containing 1 (CLDND1) is homologous to this family and localizes to TJs and the cytoplasm when exogenously expressed in cultured epithelial cell lines. Furthermore, serum antibody levels of CLDND1-derived peptides are elevated in patients with cerebral infection, cardiovascular disease, or diabetes mellitus as compared to healthy controls. However, CLDND1 transcriptional regulation remains poorly analyzed and most regional transcription factor binding sites remain to be defined...
January 27, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28098217/disrupting-hepatocyte-cyp51-from-cholesterol-synthesis-leads-to-progressive-liver-injury-in-the-developing-mouse-and-decreases-rorc-signalling
#4
Žiga Urlep, Gregor Lorbek, Martina Perše, Jera Jeruc, Peter Juvan, Madlen Matz-Soja, Rolf Gebhardt, Ingemar Björkhem, Jason A Hall, Richard Bonneau, Dan R Littman, Damjana Rozman
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H(Cyp51-/-)) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095742/lithium-response-in-bipolar-disorders-and-core-clock-genes-expression
#5
Pierre A Geoffroy, Emmanuel Curis, Cindie Courtin, Jeverson Moreira, Thomas Morvillers, Bruno Etain, Jean-Louis Laplanche, Frank Bellivier, Cynthia Marie-Claire
OBJECTIVES: We examine if the lithium response is associated with changes in core clock genes expressions. METHODS: The effect of a therapeutic concentration of lithium (1mM) on the expression levels of 17 circadian genes, was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of BD patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) were conducted at 2, 4 and 8 days (d2, d4, d8) with and without lithium exposure...
January 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28051153/the-metastasis-suppressor-rarres3-as-an-endogenous-inhibitor-of-the-immunoproteasome-expression-in-breast-cancer-cells
#6
Alison M Anderson, Murugan Kalimutho, Sarah Harten, Devathri M Nanayakkara, Kum Kum Khanna, Mark A Ragan
In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28042538/rora-and-autism-in-the-isfahan-population-is-there-an-epigenetic-relationship
#7
Mansoor Salehi, Elahe Kamali, Mojgan Karahmadi, Seyyed Mohammad Mousavi
OBJECTIVE: Autism is a neurodevelopmental disorder characterized by difficulty in verbal and non-verbal communication, impaired social interaction, and restricted and repetitive behavior. It has been recently introduced as a multigenic disorder with significant epigenetic effects on its pathology. Recently, epigenetic silencing of retinoic acid receptor- related orphan receptor alpha (RORα) gene (which has an essential role in neural tissue development) was shown to have occurred in autistic children due to methylation of its promoter region...
2017: Cell Journal
https://www.readbyqxmd.com/read/27932211/a-novel-class-of-somatic-mutations-in-blood-detected-preferentially-in-cd8-cells
#8
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
December 5, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27629369/genome-wide-association-study-of-loneliness-demonstrates-a-role-for-common-variation
#9
Jianjun Gao, Lea K Davis, Amy B Hart, Sandra Sanchez-Roige, Lide Han, John T Cacioppo, Abraham A Palmer
Loneliness is a complex biological trait that has been associated with numerous negative health outcomes. The measurement and environmental determinants of loneliness are well understood, but its genetic basis is not. Previous studies have estimated the heritability of loneliness between 37 and 55% using twins and family-based approaches, and have explored the role of specific candidate genes. We used genotypic and phenotypic data from 10 760 individuals aged ⩾50 years that were collected by the Health and Retirement Study (HRS) to perform the first genome-wide association study of loneliness...
October 12, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27566064/behavioral-and-molecular-effects-of-prenatal-continuous-light-exposure-in-the-adult-rat
#10
Suzana Elena Voiculescu, Diana Le Duc, Adrian Eugen Roșca, Vlad Zeca, Diana Maria Chiţimuș, Andreea Letiţia Arsene, Cristina Manuela Drăgoi, Alina Crenguţa Nicolae, Leon Zăgrean, Torsten Schöneberg, Ana-Maria Zăgrean
Disruption of the maternal environment during pregnancy leads to behavioral changes and diseases in the adult offspring. To explore the influence of prenatal continuous light exposure (PCLE) on the adult offspring, we exposed pregnant Wistar rats to constant light during late gestation. Adult PCLE offspring showed an anxiety-like behavior and impairment of short-term memory in different tests. Measurements in the whole brain homogenates from newborn and adult offspring indicated decreased melatonin and serotonin levels and increased reactive oxygen species level in PCLE offspring...
November 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27556492/genetic-variants-of-retinoic-acid-receptor-related-orphan-receptor-alpha-determine-susceptibility-to-type-2-diabetes-mellitus-in-han-chinese
#11
Yuwei Zhang, Yulan Liu, Yin Liu, Yanjie Zhang, Zhiguang Su
Retinoic acid receptor-related orphan receptor alpha (RORA) plays a key role in the regulation of lipid and glucose metabolism and insulin expression that are implicated in the development of type 2 diabetes mellitus (T2DM). However, the effects of genetic variants in the RORA gene on the susceptibility to T2DM remain unknown. Nine tagging single-nucleotide polymorphisms (SNPs) were screened by using the SNaPshot method in 427 patients with T2DM and 408 normal controls. Association between genotypes and haplotypes derived from these SNPs with T2DM was analyzed using different genetic models...
2016: Genes
https://www.readbyqxmd.com/read/27553600/lymphocytic-cytokine-and-transcriptomic-profiles-in-peripheral-blood-of-dogs-with-atopic-dermatitis
#12
Alicja Majewska, Małgorzata Gajewska, Kourou Dembele, Henryk Maciejewski, Adam Prostek, Michał Jank
BACKGROUND: Canine atopic dermatitis (cAD) is a common chronic and pruritic skin disease in dogs. The development of cAD involves complex interactions between environmental antigens, genetic predisposition and a number of disparate cell types. The aim of the present study was to perform comprehensive analyses of peripheral blood of AD dogs in relation to healthy subjects in order to determine the changes which would be characteristic for cAD. RESULTS: The number of cells in specific subpopulations of lymphocytes was analyzed by flow cytometry, concentration of chosen pro- and anti-inflammatory cytokines (IL-4, IL-10, IL-13, TNF-α, TGF-β1) was determined by ELISA; and microarray analysis was performed on RNA samples isolated from peripheral blood nuclear cells of AD and healthy dogs...
August 23, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27530627/variations-in-t-cell-transcription-factor-gene-structure-and-expression-associated-with-the-two-disease-forms-of-sheep-paratuberculosis
#13
Louise Nicol, Hazel Wilkie, Anton Gossner, Craig Watkins, Robert Dalziel, John Hopkins
Two different forms of clinical paratuberculosis in sheep are recognised, related to the level of bacterial colonization. Paucibacillary lesions are largely composed of lymphocytes with few bacteria, and multibacillary pathology is characterized by heavily-infected macrophages. Analysis of cytokine transcripts has shown that inflammatory Th1/Th17 T cells are associated with development of paucibacillary pathology and Th2 cytokines are correlated with multibacillary disease. The master regulator T cell transcription factors TBX21, GATA3, RORC2 and RORA are critical for the development of these T cell subsets...
2016: Veterinary Research
https://www.readbyqxmd.com/read/27438145/prexasertib-a-chk1-chk2-inhibitor-increases-the-effectiveness-of-conventional-therapy-in-b-t-cell-progenitor-acute-lymphoblastic-leukemia
#14
Andrea Ghelli Luserna Di Rorà, Ilaria Iacobucci, Enrica Imbrogno, Cristina Papayannidis, Enrico Derenzini, Anna Ferrari, Viviana Guadagnuolo, Valentina Robustelli, Sarah Parisi, Chiara Sartor, Maria Chiara Abbenante, Stefania Paolini, Giovanni Martinelli
During the last few years many Checkpoint kinase 1/2 (Chk1/Chk2) inhibitors have been developed for the treatment of different type of cancers. In this study we evaluated the efficacy of the Chk 1/2 inhibitor prexasertib mesylate monohydrate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) as single agent and in combination with other drugs. The prexasertib reduced the cell viability in a dose and time dependent manner in all the treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of γH2A...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27420620/-regulation-of-abca1-and-abcg1-gene-expression-in-the-intraabdominal-adipose-tissue
#15
V V Miroshnikova, A A Panteleeva, E A Bazhenova, E P Demina, T S Usenko, M A Nikolaev, I A Semenova, A E Neimark, J He, O D Belyaeva, O A Berkovich, E I Baranova, S N Pchelina
Tissue specific expression of genes encoding cholesterol transporters ABCA1 and ABCG1 as well as genes encoding the most important transcriptional regulators of adipogenesis - LXRa, LXRb, PPARg and RORa has been investigated in intraabdominal adipose tissue (IAT) samples.A direct correlation between the content of ABCA1 and ABCG1 proteins with RORa protein level (r=0.480, p<0.05; r=0.435, p<0.05, respectively) suggests the role of the transcription factor RORa in the regulation of IAT ABCA1 and ABCG1 protein levels...
March 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/27391931/automating-recession-curve-displacement-recharge-estimation
#16
Brennan Smith, Stuart Schwartz
Recharge estimation is an important and challenging element of groundwater management and resource sustainability. Many recharge estimation methods have been developed with varying data requirements, applicable to different spatial and temporal scales. The variability and inherent uncertainty in recharge estimation motivates the recommended use of multiple methods to estimate and bound regional recharge estimates. Despite the inherent limitations of using daily gauged streamflow, recession curve displacement methods provide a convenient first-order estimate as part of a multimethod hierarchical approach to estimate watershed-scale annual recharge...
January 2017: Ground Water
https://www.readbyqxmd.com/read/27374490/discovery-and-structural-optimization-of-4-4-benzyloxy-phenyl-3-4-dihydropyrimidin-2-1h-ones-as-rorc-inverse-agonists
#17
Xi-Shan Wu, Rui Wang, Yan-Li Xing, Xiao-Qian Xue, Yan Zhang, Yong-Zhi Lu, Yu Song, Xiao-Yu Luo, Chun Wu, Yu-Lai Zhou, Jian-Qin Jiang, Yong Xu
AIM: Retinoic acid receptor-related orphan nuclear receptors (RORs) are orphan nuclear receptors that show constitutive activity in the absence of ligands. Among 3 subtypes of RORs, RORc is a promising therapeutic target for the treatment of Th17-mediated autoimmune diseases. Here, we report novel RORc inverse agonists discovered through structure-based drug design. METHODS: Based on the structure of compound 8, a previously described agonist of RORa, a series of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives were designed and synthesized...
November 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27324142/circadian-genes-and-lithium-response-in-bipolar-disorders-associations-with-ppargc1a-pgc-1%C3%AE-and-rora
#18
P A Geoffroy, B Etain, M Lajnef, E-H Zerdazi, C Brichant-Petitjean, U Heilbronner, L Hou, F Degenhardt, M Rietschel, F J McMahon, T G Schulze, S Jamain, C Marie-Claire, F Bellivier
Preliminary studies suggest that lithium (Li) response might be associated with some circadian gene polymorphisms, we therefore performed a pharmacogenetic study on the core clock genes in two independent samples suffering from bipolar disorder (BD) and thoroughly characterized for their Li response. Two independent Caucasian samples (165 and 58 bipolar patients) treated with Li were selected from samples recruited in a French multicenter study and assessed for their Li response using the Alda scale. The two samples were genotyped using the Human660 (H660) and OmniExpress (OE) BeadChips and gene-based association analyses of 22 core clock genes were conducted...
September 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27302879/identification-of-master-regulator-genes-in-human-periodontitis
#19
A D Sawle, M Kebschull, R T Demmer, P N Papapanou
Analytic approaches confined to fold-change comparisons of gene expression patterns between states of health and disease are unable to distinguish between primary causal disease drivers and secondary noncausal events. Genome-wide reverse engineering approaches can facilitate the identification of candidate genes that may distinguish between causal and associative interactions and may account for the emergence or maintenance of pathologic phenotypes. In this work, we used the algorithm for the reconstruction of accurate cellular networks (ARACNE) to analyze a large gene expression profile data set (313 gingival tissue samples from a cross-sectional study of 120 periodontitis patients) obtained from clinically healthy (n = 70) or periodontitis-affected (n = 243) gingival sites...
August 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27301432/promoter-hypomethylation-of-rar-related-orphan-receptor-%C3%AE-1-is-correlated-with-unfavorable-clinicopathological-features-in-patients-with-colorectal-cancer
#20
Hisao Kano, Tadatoshi Takayama, Yutaka Midorikawa, Hiroki Nagase
Retinoic acid receptor-related orphan receptor α (RORA) is a tumor-specific differentially methylated region. RORA mRNA expression is frequently downregulated in colorectal cancer (CRC) due to promoter methylation, and this methylation is correlated with the development of CRC. Here we investigated the correlation between the methylation status of the RORA promoter region and clinical CRC stages. The methylation status of RORA isoform 1 (RORA1) and isoform 4 (RORA4) promoters was investigated in 43 paired CRC specimens and adjacent normal tissues by quantitative DNA methylation analysis using the Sequenom MassARRAY system and bisulfite sequencing...
July 19, 2016: Bioscience Trends
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