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https://www.readbyqxmd.com/read/29892907/how-a-single-5-methylation-of-cytosine-regulates-the-recognition-of-c-ebp%C3%AE-transcription-factor-a-molecular-dynamic-simulation-study
#1
Lihua Bie, Likai Du, Qiaoxia Yuan, Jun Gao
CpG methylation can regulate gene expression by altering the specific binding of protein and DNA. In order to understand how a single 5mC regulates protein-DNA interactions, we have compared the structures and dynamics of CEBP/βprotein-DNA complexes before and after methylation, and the results indicate that even a single 5mC can regulate protein-DNA recognition by steric-hindrance effect of methyl group and changing the hydrogen bond interactions. The interactions between the methyl group, mCpG motif, and the conserved residue arginine make the protein read out the variation of local environment, which further enhances the specific recognition and affects the base pair stacking...
June 11, 2018: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29884649/impaired-dna-demethylation-of-c-ebp-sites-causes-premature-aging
#2
Andrea Schäfer, Bernadette Mekker, Medhavi Mallick, Viviana Vastolo, Emil Karaulanov, Dominik Sebastian, Carina von der Lippen, Bernd Epe, Damien J Downes, Carola Scholz, Christof Niehrs
Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp ( CCAAT/enhancer-binding protein ) mutants...
June 8, 2018: Genes & Development
https://www.readbyqxmd.com/read/29773596/card10-a-cebpe-target-involved-in-granulocytic-differentiation
#3
Pavithra Shyamsunder, Haresh Sankar, Anand Mayakonda, Lin Han, Hazimah Binte Mohd Nordin, Teoh Weoi Woon, Mahalakshmi Shanmugasundaram, Pushkar Dakle, Vikas Madan, H Phillip Koeffler
Maturation of granulocytes is dependent on controlled gene expression by myeloid lineage restricted transcription factors. CEBPE is one of the essential transcription factors required for granulocytic differentiation. Identification of downstream targets of CEBPE is vital to understand better its role in terminal granulopoiesis. In this study, we have identified Card10 as a novel target of CEBPE. We show that CEBPE binds to regulatory elements upstream of the murine Card10 locus, and expression of CARD10 is significantly reduced in Cebpe knock-out mice...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772680/the-crosstalk-of-endoplasmic-reticulum-er-stress-pathways-with-nf-%C3%AE%C2%BAb-complex-mechanisms-relevant-for-cancer-inflammation-and-infection
#4
REVIEW
M Lienhard Schmitz, M Samer Shaban, B Vincent Albert, Anke Gökçen, Michael Kracht
Stressful conditions occuring during cancer, inflammation or infection activate adaptive responses that are controlled by the unfolded protein response (UPR) and the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) signaling pathway. These systems can be triggered by chemical compounds but also by cytokines, toll-like receptor ligands, nucleic acids, lipids, bacteria and viruses. Despite representing unique signaling cascades, new data indicate that the UPR and NF-κB pathways converge within the nucleus through ten major transcription factors (TFs), namely activating transcription factor (ATF)4, ATF3, CCAAT/enhancer-binding protein (CEBP) homologous protein (CHOP), X-box-binding protein (XBP)1, ATF6α and the five NF-κB subunits...
May 16, 2018: Biomedicines
https://www.readbyqxmd.com/read/29761173/liver-enriched-transcription-factor-expression-relates-to-chronic-hepatic-failure-in-humans
#5
Jorge Guzman-Lepe, Eduardo Cervantes-Alvarez, Alexandra Collin de l'Hortet, Yang Wang, Wendy M Mars, Yoshinao Oda, Yuki Bekki, Masahiro Shimokawa, Huanlin Wang, Tomoharu Yoshizumi, Yoshihiko Maehara, Aaron Bell, Ira J Fox, Kazuki Takeishi, Alejandro Soto-Gutierrez
The mechanisms by which the liver fails in end-stage liver disease remain elusive. Disruption of the transcription factor network in hepatocytes has been suggested to mediate terminal liver failure in animals. However, this hypothesis remains unexplored in human subjects. To study the relevance of transcription factor expression in terminal stages of chronic liver failure in humans, we analyzed the expression of liver-enriched transcription factors (LETFs) hepatocyte nuclear factor (HNF)4α, HNF1α, forkhead box protein A2 (FOXA2), CCAAT/enhancer-binding protein (CEBP)α, and CEBPβ...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29721149/low-frequency-intermittent-hypoxia-promotes-subcutaneous-adipogenic-differentiation
#6
Yan Wang, Judith C W Mak, Mary Y K Lee, Aimin Xu, Mary S M Ip
Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is associated with obesity and metabolic disorders. The mass and function of adipose tissue are largely dependent on adipogenesis. The impact of low-frequency IH on adipogenesis is unknown. Sprague-Dawley rats were subjected to IH (4 min for 10% O2 and 2 min for 21% O2 ) or intermittent normoxia (IN) for 6 weeks. The degree of adipogenic differentiation was evaluated by adipogenic transcriptional factors, adipocyte-specific proteins, and oily droplet production in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29720835/combination-of-garcinia-cambogia-extract-and-pear-pomace-extract-additively-suppresses-adipogenesis-and-enhances-lipolysis-in-3t3-l1-cells
#7
Kushal Sharma, Siwon Kang, Dalseong Gong, Sung-Hwa Oh, Eun-Young Park, Min-Ho Oak, Eunyoung Yi
Background: Inhibition of adipogenesis has been a therapeutic target for reducing obesity and obesity-related disorders such as diabetes, hypertension, atherosclerosis, and cancer. For decades, anti-adipogenic potential of many herbal extracts has been investigated. One example is Garcinia cambogia extract (GE) containing (-)-hydroxycitric acid as an active ingredient. GE is currently marketed as a weight loss supplement, used alone or with other ingredients. Pear pomace extract (PE), another natural product, has been also shown to have anti-adipogenic activity in a recent report...
April 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29695233/apigetrin-inhibits-adipogenesis-in-3t3-l1-cells-by-downregulating-ppar%C3%AE-and-cebp-%C3%AE
#8
Fatma Hadrich, Sami Sayadi
BACKGROUND: Apigetrin, a flavonoid found in many plant leaves and seeds, has been known to possess antimutagenic, anti-cancer, antioxidant and anti-inflammatory properties. Here, we are investigating the effect of the apigetrin on adipocytes differentiation in 3T3-L1 adipocytes, and elucidating the mechanism of its action. METHODS: Lipids accumulation was measured by Oil Red O staining and cell cycle was analyzed by flow cytometry. The antioxidant effect of apigetrin was evaluated against hydrogen peroxide...
April 25, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29651288/-cebpe-mutant-specific-granule-deficiency-correlates-with-aberrant-granule-organization-and-substantial-proteome-alterations-in-neutrophils
#9
Nina K Serwas, Jakob Huemer, Régis Dieckmann, Ester Mejstrikova, Wojciech Garncarz, Jiri Litzman, Birgit Hoeger, Ondrej Zapletal, Ales Janda, Keiryn L Bennett, Renate Kain, Dontscho Kerjaschky, Kaan Boztug
Specific granule deficiency (SGD) is a rare disorder characterized by abnormal neutrophils evidenced by reduced granules, absence of granule proteins, and atypical bilobed nuclei. Mutations in CCAAT/enhancer-binding protein-ε ( CEBPE ) are one molecular etiology of the disease. Although C/EBPε has been studied extensively, the impact of CEBPE mutations on neutrophil biology remains elusive. Here, we identified two SGD patients bearing a previously described heterozygous mutation (p.Val218Ala) in CEBPE . We took this rare opportunity to characterize SGD neutrophils in terms of granule distribution and protein content...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29506519/rnaseq-analysis-of-bronchial-epithelial-cells-to-identify-copd-associated-genes-and-snps
#10
Jiyoun Yeo, Diego A Morales, Tian Chen, Erin L Crawford, Xiaolu Zhang, Thomas M Blomquist, Albert M Levin, Pierre P Massion, Douglas A Arenberg, David E Midthun, Peter J Mazzone, Steven D Nathan, Ronald J Wainz, Patrick Nana-Sinkam, Paige F S Willey, Taylor J Arend, Karanbir Padda, Shuhao Qiu, Alexei Federov, Dawn-Alita R Hernandez, Jeffrey R Hammersley, Youngsook Yoon, Fadi Safi, Sadik A Khuder, James C Willey
BACKGROUND: There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD. METHODS: To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0...
March 5, 2018: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29415693/elucidating-mechanistic-insights-into-drug-action-for-atopic-dermatitis-a-systems-biology-approach
#11
Indhupriya Subramanian, Vivek K Singh, Abhay Jere
BACKGROUND: Topical Betamethasone (BM) and Pimecrolimus (PC) are widely used drugs in the treatment of atopic dermatitis (AD). Though the biomolecules and biological pathways affected by the drugs are known, the causal inter-relationships among these pathways in the context of skin is not available. We aim to derive this insight by using transcriptomic data of AD skin samples treated with BM and PC using systems biology approach. METHODS: Transcriptomic datasets of 10 AD patients treated with Betamethasone and Pimecrolimus were obtained from GEO datasets...
February 7, 2018: BMC Dermatology
https://www.readbyqxmd.com/read/29335448/regional-evaluation-of-childhood-acute-lymphoblastic-leukemia-genetic-susceptibility-loci-among-japanese
#12
Kevin Y Urayama, Masatoshi Takagi, Takahisa Kawaguchi, Keitaro Matsuo, Yoichi Tanaka, Yoko Ayukawa, Yuki Arakawa, Daisuke Hasegawa, Yuki Yuza, Takashi Kaneko, Yasushi Noguchi, Yuichi Taneyama, Setsuo Ota, Takeshi Inukai, Masakatsu Yanagimachi, Dai Keino, Kazutoshi Koike, Daisuke Toyama, Yozo Nakazawa, Hidemitsu Kurosawa, Kozue Nakamura, Koichi Moriwaki, Hiroaki Goto, Yujin Sekinaka, Daisuke Morita, Motohiro Kato, Junko Takita, Toshihiro Tanaka, Johji Inazawa, Katsuyoshi Koh, Yasushi Ishida, Akira Ohara, Shuki Mizutani, Fumihiko Matsuda, Atsushi Manabe
Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years) previously enrolled onto a Tokyo Children's Cancer Study Group trial were collected during 2013-2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29236325/aml1-eto-trans-activates-c-kit-expression-through-the-long-range-interaction-between-promoter-and-intronic-enhancer
#13
Ying Tian, Genjie Wang, Qingzhu Hu, Xichun Xiao, Shuxia Chen
The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT...
April 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29217197/effect-of-lncrna-hoxa11-as1-on-adipocyte-differentiation-in-human-adipose-derived-stem-cells
#14
Nuerbiye Nuermaimaiti, Jie Liu, Xiaodi Liang, Yi Jiao, Dan Zhang, Ling Liu, Xuanyu Meng, Yaqun Guan
AIMS: To determine the role of lncRNA HOXA11-AS1 on adipocyte differentiation. METHODS: Human adipose-derived stem cells (hADSCs) were isolated from adipose tissues of patients and cultured in vitro, followed by knockdown of HOXA11-AS1. Then, adipocyte differentiation and expression of adipogenic-related genes (CEBP-α, DGAT2, CIDEC, and perilipin) were measured by RT-qPCR and Western blot. RESULTS: We demonstrated that knockdown of HOXA11-AS1 inhibited adipocyte differentiation, leading to suppression of adipogenic-related gene (CEBP-α, DGAT2, CIDEC, and perilipin) transcription, as well as decreased lipid accumulation in hADSCs...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28905228/genetic-susceptibility-in-childhood-acute-lymphoblastic-leukemia
#15
REVIEW
Angela Gutierrez-Camino, Idoia Martin-Guerrero, Africa García-Orad
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading cause of death due to disease in children. The genetic basis of ALL susceptibility has been supported by its association with certain congenital disorders and, more recently, by several genome-wide association studies (GWAS). These GWAS identified common variants in ARID5B, IKZF1, CEBPE, CDKN2A, PIP4K2A, LHPP and ELK3 influencing ALL risk. However, the risk variants of these SNPs were not validated in all populations, suggesting that some of the loci could be population specific...
September 13, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28858301/activation-of-aldehyde-dehydrogenase-2-slows-down-the-progression-of-atherosclerosis-via-attenuation-of-er-stress-and-apoptosis-in-smooth-muscle-cells
#16
Mei-Yan Yang, Ya-Bin Wang, Bo Han, Bo Yang, Yu-Wei Qiang, Yan Zhang, Zhao Wang, Xu Huang, Jie Liu, Yun-Dai Chen, Jun Ren, Feng Cao, Yong Xu
Aldehyde dehydrogenase 2 (ALDH2) is a key mitochondrial enzyme in the metabolism of aldehydes and may have beneficial cardiovascular effects for conditions such as cardiac hypertrophy, heart failure, myocardial I/R injury, reperfusion, arrhythmia, coronary heart disease and atherosclerosis. In this study we investigated the role of ALDH2 in the progression of atherosclerosis and the underlying mechanisms, with a focus on endoplasmic reticulum (ER) stress. A clinical study was performed in 248 patients with coronary heart disease...
January 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28853918/human-bronchial-epithelial-cell-derived-factors-from-severe-asthmatic-subjects-stimulate-eosinophil-differentiation
#17
Brittany M A Salter, Steven G Smith, Manali Mukherjee, Sophie Plante, Sakktee Krisna, Graeme Nusca, John Paul Oliveria, Anam Irshad, Gail M Gauvreau, Jamila Chakir, Parameswaran Nair, Roma Sehmi
Activated bronchial epithelial cells (BEC) release various alarmins, including thymic stromal lymphopoietin (TSLP), that drive type 2 inflammation. We hypothesize that BEC-derived factors promote in situ eosinophil differentiation and maturation, a process that is driven by an IL-5-rich microenvironment in asthmatic airways. To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived nonadherent mononuclear cells incubated with BEC supernatants (BECSN) from healthy nonatopic controls (n = 8), mild atopic asthmatics (n = 9), and severe asthmatics (n = 5)...
January 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28768142/contributions-of-ikzf1-ddc-cdkn2a-cebpe-and-lmo1-gene-polymorphisms-to-acute-lymphoblastic-leukemia-in-a-yemeni-population
#18
Boshra Al-Absi, Muhammad F M Razif, Suzita M Noor, Riyadh Saif-Ali, Mohammed Aqlan, Sameer D Salem, Radwan H Ahmed, Sekaran Muniandy
BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent...
October 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28756227/low-dose-g-csf-improves-fat-graft-retention-by-mobilizing-endogenous-stem-cells-and-inducing-angiogenesis-whereas-high-dose-g-csf-inhibits-adipogenesis-with-prolonged-inflammation-and-severe-fibrosis
#19
Junrong Cai, Bin Li, Kaiyang Liu, Jingwei Feng, Kai Gao, Feng Lu
BACKGROUND: Hematopoietic stem cells (HSCs) promote fat graft survival by modulating its revascularization. The authors hypothesize that mobilization of HSCs by G-CSF will improve fat graft survival. Hence, we evaluated the effect of different doses of G-CSF on fat grafting. METHODS: Male 8-week-old C57 mice received high-dose G-CSF (100 μg/kg), low-dose G-CSF (10 μg/kg), and PBS (control) intraperitoneally for 7 consecutive days right after autologous fat grafting...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751478/novel-gene-and-network-associations-found-for-acute-lymphoblastic-leukemia-using-case-control-and-family-based-studies-in-multiethnic-populations
#20
Priyanka Nakka, Natalie P Archer, Heng Xu, Philip J Lupo, Benjamin J Raphael, Jun J Yang, Sohini Ramachandran
Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, suggesting that germline variants influence ALL risk. Although multiple genome-wide association (GWA) studies have identified variants predisposing children to ALL, it remains unclear whether genetic heterogeneity affects ALL susceptibility and how interactions within and among genes containing ALL-associated variants influence ALL risk.Methods: Here, we jointly analyzed two published datasets of case-control GWA summary statistics along with germline data from ALL case-parent trios...
October 2017: Cancer Epidemiology, Biomarkers & Prevention
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