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https://www.readbyqxmd.com/read/28670633/the-orphan-nuclear-receptor-ror-alpha-and-group-3-innate-lymphoid-cells-drive-fibrosis-in-a-mouse-model-of-crohn-s-disease
#1
Bernard C Lo, Matthew J Gold, Michael R Hughes, Frann Antignano, Yanet Valdez, Colby Zaph, Kenneth W Harder, Kelly M McNagny
Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that Rora-deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition and reduced fibroblast accumulation...
September 2, 2016: Science Immunology
https://www.readbyqxmd.com/read/28617945/microrna-cluster-106a-363-is-involved-in-t-helper-17-th17-cell-differentiation
#2
Marc Kaestle, Sabine Bartel, Kerstin Geillinger-Kästle, Martin Irmler, Johannes Beckers, Bernhard Ryffel, Oliver Eickelberg, Susanne Krauss-Etschmann
T-helper cell 17 (Th17) mediated inflammation is associated with various diseases including autoimmune encephalitis, inflammatory bowel disease and lung diseases such as chronic obstructive pulmonary disease and asthma. Differentiation into distinct Th subtypes needs to be tightly regulated to ensure an immunological balance. As microRNAs (miRNAs) are critical regulators of signaling pathways, we aimed to identify specific miRNAs implicated in controlling Th17 differentiation. We were able to create a regulatory network model of murine Th cell differentiation by combining Affymetrix mRNA and miRNA arrays and in-silico analysis...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#3
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608249/retinoic-acid-related-orphan-receptor-alpha-rora-variants-are-associated-with-autism-spectrum-disorder
#4
Arezou Sayad, Rezvan Noroozi, Mir Davood Omrani, Mohammad Taheri, Soudeh Ghafouri-Fard
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with various epidemiologic, genetic, epigenetic, and environmental factors being associated with it. The observed sex bias in ASD towards male has prompted investigators to propose sex-dependent mechanisms for ASD. Retinoic acid-related orphan receptor-alpha (RORA) is a new autism candidate gene that has been shown to be differentially regulated by male and female hormones. Previous studies have shown deregulation of its expression in the prefrontal cortex and the cerebellum of ASD patients...
June 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28607111/a-distinct-inhibitory-function-for-mir-18a-in-th17-cell-differentiation
#5
Misty M Montoya, Julia Maul, Priti B Singh, Heather H Pua, Frank Dahlström, Nanyan Wu, Xiaozhu Huang, K Mark Ansel, Dirk Baumjohann
Th17 cell responses orchestrate immunity against extracellular pathogens but also underlie autoimmune disease pathogenesis. In this study, we uncovered a distinct and critical role for miR-18a in limiting Th17 cell differentiation. miR-18a was the most dynamically upregulated microRNA of the miR-17-92 cluster in activated T cells. miR-18a deficiency enhanced CCR6(+) RAR-related orphan receptor (ROR)γt(+) Th17 cell differentiation in vitro and increased the number of tissue Th17 cells expressing CCR6, RORγt, and IL-17A in airway inflammation models in vivo...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28598825/retinoic-acid-related-orphan-receptor-alpha-rora-variants-and-risk-of-breast-cancer
#6
Mohammad Taheri, Mir Davood Omrani, Rezvan Noroozi, Shaghayegh Sarrafzadeh, Soudeh Ghafouri-Fard, Arezou Sayad
BACKGROUND: Breast cancer is the most common type of cancer and the second leading cause of cancer death in females. Despite numerous studies in this field, the etiology and clinical behavior of breast tumors have not been understood yet. Retinoid orphan nuclear receptor alpha (RORA) is a member of the orphan nuclear factor family involved in the regulation of lipid and steroid metabolism, immune response and circadian rhythms. Recent evidences support its role as a tumor suppressor gene...
June 2, 2017: Breast Disease
https://www.readbyqxmd.com/read/28596594/magnifying-narrow-band-imaging-of-gastric-mucosal-morphology-predicts-the-h-pylori-related-epigenetic-field-defect
#7
Tomomitsu Tahara, Jumpei Yamazaki, Sayumi Tahara, Masaaki Okubo, Tomohiko Kawamura, Noriyuki Horiguchi, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
DNA methylation is associated with "field defect" in the gastric mucosa. To characterize "field defect" morphologically, we examined DNA methylation of non-neoplastic gastric mucosa in relation to their morphology seen by narrow-band imaging (NBI) with magnifying endoscopy. Magnifying NBI of non-neoplastic gastric body was classified as follows: normal-small and round pits with uniform subepithelial capillary networks; type 1-a little enlarged round pits with indistinct subepithelial capillary networks; type 2-remarkably enlarged pits with irregular vessels; and type 3-clearly demarcated oval or tubulovillous pits with bulky coiled or wavy vessels...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28557342/morphologic-characterization-of-residual-dna-methylation-in-the-gastric-mucosa-after-helicobacter-pylori-eradication
#8
Sayumi Tahara, Tomomitsu Tahara, Tetsuya Tuskamoto, Noriyuki Horiguchi, Tomohiko Kawamura, Masaaki Okubo, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
Residual DNA methylation in the gastric mucosa after Helicobacter pylori (H. pylori) eradication may have a role in gastric carcinogenesis. We examined the association between morphologic features and promoter methylation status of non-neoplastic gastric mucosa especially after H. pylori eradication. A total of 140 gastric specimens from 99 participants who had at least 6 months of post-eradication period were examined. The magnifying narrow-band imaging (NBI) endoscopic feature of gastric mucosa was divided into two types: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28545453/genome-wide-methylation-analysis-reveals-differentially-methylated-loci-that-are-associated-with-an-age-dependent-increase-in-bovine-fibroblast-response-to-lps
#9
Filiz T Korkmaz, David E Kerr
BACKGROUND: Differences in DNA methylation are known to contribute to the development of immune-related disorders in humans but relatively little is known about how methylation regulates immune function in cattle. Utilizing whole-transcriptome analyses of bovine dermal fibroblasts, we have previously identified an age and breed-dependent up-regulation of genes within the toll-like receptor 4 (TLR4) pathway that correlates with enhanced fibroblast production of IL-8 in response to lipopolysaccharide (LPS)...
May 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28506283/prolactin-blocks-the-expression-of-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-and-reduces-osteoclastogenesis-and-bone-loss-in-murine-inflammatory-arthritis
#10
Maria G Ledesma-Colunga, Norma Adán, Georgina Ortiz, Mariana Solís-Gutiérrez, Fernando López-Barrera, Gonzalo Martínez de la Escalera, Carmen Clapp
BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28487311/egr2-and-3-control-adaptive-immune-responses-by-temporally-uncoupling-expansion-from-t-cell-differentiation
#11
Tizong Miao, Alistair L J Symonds, Randeep Singh, Janine D Symonds, Ane Ogbe, Becky Omodho, Bo Zhu, Suling Li, Ping Wang
Egr2 and 3 are important for maintaining immune homeostasis. Here we define a fundamental function of Egr2 and 3 operating as a checkpoint that controls the transition between clonal expansion and differentiation of effector T cells. Egr2 and 3 deficiency resulted in defective clonal expansion but hyperactivation and excessive differentiation of T cells in response to viral infection. Conversely, sustained Egr2 expression enhanced expansion but severely impaired effector differentiation. Egr2 bound to and controlled the expression of genes regulating proliferation (Myc and Myb) and differentiation repressors (Bcl6, Id3), while repressing transcription factors required for effector function (Zeb2, RORa, RORc, and Bhlhe40)...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28455490/1-25-oh-2d3-protects-liver-fibrosis-through-decreasing-the-generation-of-th17-cells
#12
Lei Gu, Qing Xu, Hui Cao
BACKGROUND The aim of this study was to study the effects of 1-alpha,25-dihydroxy-cholecalcifero (1,25(OH)2D3) on liver fibrosis and the generation of Th17 cells in vivo and in vitro. MATERIAL AND METHODS Thirty C57 mice were randomly divided into control, model, and treatment groups. Hepatic fibrosis was induced by subcutaneous injection of CCl4. Liver fibrosis condition was evaluated through pathological inspection and blood biochemical examination of liver function. Immunohistochemical assays were used to detect the expression of α-SMA, TGF-β, and collagen I to observe hepatic stellate cell activation level...
April 29, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28421310/comparison-of-selected-protein-levels-in-tumour-and-surgical-margin-in-a-group-of-patients-with-oral-cavity-cancer
#13
Joanna Katarzyna Strzelczyk, Karolina Gołąbek, Piotr Cuber, Łukasz Krakowczyk, Aleksander Jerzy Owczarek, Martyna Fronczek, Piotr Choręża, Edyta Hudziec, Zofia Ostrowska
Oral cavity cancer belongs to head-and-neck squamous cell carcinoma group. The purpose of the study was to assess the levels of certain proteins in a tumour and surgical margin in a group of patients with oral cavity cancer. The levels of DAPK1, MGMT, CDH1, SFRP1, SFRP2, RORA, TIMP3, p16, APC and RASSF1 proteins were measured by ELISA in tissue homogenates. The protein levels of DAPK1, MGMT, CDH1, SFRP2 and RASSF1 were significantly higher in tumour tissue than in the margin, contrary to TIMP3 which was lower in the tumour itself...
April 18, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28412756/effects-of-circadian-clock-genes-and-environmental-factors-on-cognitive-aging-in-old-adults-in-a-taiwanese-population
#14
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Shih-Jen Tsai
Previous animal studies have indicated associations between circadian clock genes and cognitive impairment . In this study, we assessed whether 11 circadian clockgenes are associated with cognitive aging independently and/or through complex interactions in an old Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to evaluate cognitive function...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28392332/type-2-innate-lymphoid-cells-disrupt-bronchial-epithelial-barrier-integrity-by-targeting-tight-junctions-through-il-13-in-asthmatic-patients
#15
Kazunari Sugita, Catherine A Steer, Itziar Martinez-Gonzalez, Can Altunbulakli, Hideaki Morita, Francesc Castro-Giner, Terufumi Kubo, Paulina Wawrzyniak, Beate Rückert, Katsuko Sudo, Susumu Nakae, Kenji Matsumoto, Liam O'Mahony, Mübeccel Akdis, Fumio Takei, Cezmi A Akdis
BACKGROUND: Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. OBJECTIVE: We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice...
April 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28386079/multimodal-regulation-orchestrates-normal-and-complex-disease-states-in-the-retina
#16
A M Olivares, A S Jelcick, J Reinecke, B Leehy, A Haider, M A Morrison, L Cheng, D F Chen, M M DeAngelis, N B Haider
Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD)...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356161/the-cell-cycle-checkpoint-inhibitors-in-the-treatment-of-leukemias
#17
REVIEW
A Ghelli Luserna di Rora', I Iacobucci, G Martinelli
The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias...
March 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28338984/e3-ubiquitin-ligases-siah1-2-regulate-hypoxia-inducible-factor-1-hif-1-mediated-th17-cell-differentiation
#18
Akiko Matsui-Hasumi, Yayoi Sato, Ayako Uto-Konomi, Satoshi Yamashita, Junji Uehori, Akihiko Yoshimura, Masakatsu Yamashita, Hiroshi Asahara, Shinobu Suzuki, Masato Kubo
IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo...
March 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28332183/retinoic-acid-receptor-related-orphan-receptor-ror%C3%AE-regulates-differentiation-and-survival-of-keratinocytes-during-hypoxia
#19
Hongyu Li, Longjian Zhou, Jun Dai
Low O2 pressures present in the microenvironment of epidermis control keratinocyte differentiation and epidermal barrier function through hypoxia inducible factors (HIFs) dependent gene expression. This study focuses on investigating relations of the retinoic acid receptor-related orphan receptor alpha (RORα) to HIF-1α in keratinocytes under hypoxic conditions. The expression level of RORα is significantly elevated under hypoxia in both human and murine keratinocytes. Gene silencing of RORA attenuates hypoxia-stimulated expression of genes related to late differentiation and epidermal barrier function, and leads to an enhanced apoptotic response...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28326728/-effect-of-clock-gene-per1-knockdown-on-clock-gene-networks-in-human-oral-squamous-cell-carcinoma
#20
Zhao Qin, Ao Yiran, Yang Kai, Su Xiaoli, Lü Xiaoqiang
OBJECTIVE: This study investigated the effect of clock gene PER1 on the expression levels of other clock genes in clock gene networks in oral squamous cell carcinoma cells. METHODS: We used RNA interference mediated by short hairpin RNAs (shRNAs) to effectively knock down PER1 in SCC15 human oral squamous cell carcinoma cells. Flow cytometry was used to detect the degree of proliferation and apoptosis of the cells after PER1 knockdown, and quantitative real-time PCR was used to detect the mRNA expression levels of the clock genes CLOCK, BMAL1, PER1, PER2, PER3, DEC1, DEC2, CRY1, CRY2, TIM, CKIE, RORA, NPAS2, and REV-ERBA...
February 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
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