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https://www.readbyqxmd.com/read/29033545/downregulation-of-a20-increases-the-cytotoxicity-of-ifn-%C3%AE-in-hepatocellular-carcinoma-cells
#1
Lei Yin, Zheng Fang, Ning-Jia Shen, Ying-He Qiu, Ai-Jun Li, Yong-Jie Zhang
Hepatocellular carcinoma (HCC) is a highly fatal disease mandating development of novel, effective therapeutic strategy. Interferon-gamma (IFN-γ) is a pleiotropic cytokine with immunomodulatory, antiviral, and antitumor effects. Although IFN-γ is a promising antitumor agent, its application is limited by resistance in tumor cells. A20 is a zinc-finger protein that was initially identified as a gene product induced by tumor necrosis factor α in human umbilical vein endothelial cells. In this study, we found that silencing of A20 combined with IFN-γ significantly represses cell viability, and induces apoptosis and cell-cycle arrest in HCC cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29029426/a20-functions-as-mediator-in-tnf%C3%AE-induced-injury-of-human-umbilical-vein-endothelial-cells-through-tak1-dependent-mapk-enos-pathway
#2
Lei Li, Bingqing Huang, Shiyang Song, Hareshwaree Sohun, Zhiheng Rao, Luyuan Tao, Qike Jin, Jingjing Zeng, Rongzhou Wu, Kangting Ji, Jiafeng Lin, Lianpin Wu, Maoping Chu
A20, a negative regulator of nuclear factor κB signaling, has been shown to attenuate atherosclerotic events. Transforming growth factor beta-activated kinase 1 (TAK1) plays a critical role in TNFα-induced atherosclerosis via endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the study, we investigated the hypothesis that A20 protected endothelial cell injury induced by TNFα through modulating eNOS activity and TAK1 signalling. Human umbilical vein endothelial cells (HUVECs) were stimulated by TNFα...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026009/inactivated-lactobacillus-promotes-the-protection-against-myocardial-ischemia-reperfusion-injury-through%C3%A2-nf-%C3%AE%C2%BA-b-pathway
#3
Ni Wang, Genhong Song, Yang Yang, Weiwei Yuan, Ming Qi
Objectives: Although restoration of blood flow to an ischemic organ is essential to prevent irreversible cellular injury, reperfusion may augment tissue injury in excess of that produced by ischemia alone. So this experiment was designed to study the protective effects and mechanism of inactivated lactobacillus (Lac) on myocardial ischemia reperfusion injury (MIRI). Methods: MIRI rat models were established by ligation of left anterior descending coronary artery for about 30 min and then, reperfusion for 120 min and divided into control group, model group and Lac (10(6), 10(7) and 10(8)cfu/kg) groups...
October 12, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28988144/intracelluar-delivery-of-a20-protein-inhibits-tnf%C3%AE-induced-nf-%C3%AE%C2%BAb-activation
#4
Hye-Rim Lee, Jin Choi, Seung Hoon Lee, Mi-La Cho, Dae-Myung Jue
A20 (also known as TNFAIP3) is a potent anti-inflammatory protein that suppresses many intracellular signaling pathways induced by inflammatory cytokines and bacterial and viral pathogens. The anti-inflammatory function of A20 depends on its modulation of or binding to polyubiquitin chains on key signaling proteins in the nuclear factor-κB (NF-κB) pathway. To test whether A20 can be used as therapeutic agent in these inflammatory diseases, we prepared a recombinant cell-penetrating form of A20 (TAT-A20) for intracellular delivery and examined its effect on tumor necrosis factor-α (TNFα)-induced NF-κB activation...
October 4, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28979136/targeted-interfering-dep-domain-containing-1-protein-induces-apoptosis-in-a549-lung-adenocarcinoma-cells-through-the-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Qingqing Wang, Aili Li, Junfei Jin, Guojin Huang
Ectopic expression of DEP domain containing 1 (DEPDC1) in lung adenocarcinomas is associated with poor prognosis, but its role and the underlying mechanism remain unknown. In this study, DEPDC1 expression in lung cancer cell lines was examined with Western blot assay, and DEPDC1-positive cell A549 was selected for further experiments. DEPDC1 inhibitor miR-130a was overexpressed in A549 cells, and the proliferation and apoptosis of these cells were analyzed with cell counting and flow cytometry assay. Interfering peptide 11R-DEP:611-628 and JNK inhibitor SP600125 were used alone or in combination to treat A549 cells, and the cell proliferation and apoptosis were assessed by flow cytometry assay; caspase 3 and cleaved caspase 3, phosphor-JNK, and total JNK were detected by Western blotting; and nuclear factor kappa B (NF-κB) localization was determined by immunofluorescence staining...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28977843/orphan-nuclear-receptor-nur77-inhibits-poly-i-c-triggered-acute-liver-inflammation-by-inducing-the-ubiquitin-editing-enzyme-a20
#6
Xiu-Ming Li, Tian-Yu Yang, Xiao-Shun He, Jing-Ru Wang, Wen-Juan Gan, Shen Zhang, Jian-Ming Li, Hua Wu
Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77(+/+)) and Nur77(-/-) mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammatory cytokines and accelerated liver injury induced by poly (I:C)/D-GalN in Nur77(-/-) mice...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974948/the-murine-factor-h-related-protein-fhr-b-promotes-complement-activation
#7
Marcell Cserhalmi, Ádám I Csincsi, Zoltán Mezei, Anne Kopp, Mario Hebecker, Barbara Uzonyi, Mihály Józsi
Factor H-related (FHR) proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH). While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28973334/p7c3-suppresses-neuroinflammation-and-protects-retinal-ganglion-cells-of-rats-from-optic-nerve-crush
#8
Hidehiro Oku, Seita Morishita, Taeko Horie, Teruyo Kida, Masashi Mimura, Shota Kojima, Tsunehiko Ikeda
Purpose: To determine whether P7C3-A20 can inhibit the phosphorylation of the mammalian target of rapamycin (mTOR), depress neuroinflammation, and protect retinal ganglion cells (RGCs) of rats from optic nerve crush (ONC). Methods: The left optic nerve was crushed, and 5.0 mg/kg/d of P7C3-A20, 1.0 mg/kg/d of rapamycin, or their vehicle was injected intraperitoneally for 3 consecutive days beginning 1 day before the ONC. The protective effects on the RGCs were determined by immunohistochemical staining for Tuj-1...
September 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28969015/depdc1-is-required-for-cell-cycle-progression-and-motility-in-nasopharyngeal-carcinoma
#9
Xuefei Feng, Chundong Zhang, Ling Zhu, Lian Zhang, Hongxia Li, Longxia He, Yan Mi, Yitao Wang, Jiang Zhu, Youquan Bu
DEP domain containing 1 (DEPDC1) is a newly identified cancer-related and cell cycle related gene and has been demonstrated as a novel therapeutic target for bladder cancer. However, the functional involvement and therapeutic potential of DEPDC1 in nasopharyngeal carcinoma (NPC) remains unclear. Our results showed that DEPDC1 was overexpressed at both mRNA and protein levels in NPC tissues compared with normal or non-tumor tissues. The siRNA-mediated DEPDC1 depletion resulted in significant inhibition of proliferation and delay in cell cycle progression in both NPC cell lines, CNE-1 and HNE-1...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967402/a-hemispherical-contact-model-for-simplifying-3d-occlusal-surfaces
#10
Miguel Castro-Garcia, Pedro Ángel Moreno-Cabello, Miguel Ángel Rubio-Paramio, Pilar Carranza-Cañadas, Geoffrey A Thompson
STATEMENT OF PROBLEM: Currently, dental articulators can recreate mandibular movements and occlusal contacts. However, whether virtual articulators can also provide information about occluding dental surfaces, functional movements, and the mandibular condyles is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the occluding surfaces on dental casts obtained from a patient and approximate them to a hemispherical contact model. Both models were tested by digitizing the Dentatus ARL dental articulator...
September 27, 2017: Journal of Prosthetic Dentistry
https://www.readbyqxmd.com/read/28923245/a20-inhibits-both-the-degradation-and-limited-processing-of-the-nf-%C3%AE%C2%BAb-p105-precursor-a-novel-additional-layer-to-its-regulator-role
#11
Dana Lapid, Shirly Lahav-Baratz, Shai Cohen
p105 plays dual roles in NF-κB signaling: it generates the active subunit p50 and in its precursor form inhibits NF-κB activation. p105 processing occurs under basal conditions and increases following signaling. IκB kinase β (IKKβ) mediates phosphorylation at the C-terminal domain of p105, leads to accelerated processing and degradation of the precursor. A20 is a dual function deubiquitinating and ubiquitin ligating enzyme, involving in turning-off the NF-κB signaling pathway. Here we show that A20 suppresses TNFα-induced proteolysis of p105...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28918014/artificial-zinc-finger-transcription-factor-of-a20-suppresses-restenosis-in-sprague-dawley-rats-after-carotid-injury-via-the-ppar%C3%AE-pathway
#12
Zhaoyou Meng, Pan Gao, Lin Chen, Jing Peng, Jialu Huang, Min Wu, Kangning Chen, Zhenhua Zhou
The inhibition of inflammation and vascular smooth muscle cell (VSMC) proliferation is an ideal strategy to suppress intimal hyperplasia after percutaneous transluminal angioplasty (PTA). Evidence has indicated that overexpression of A20 suppresses neointima formation, but its low transfection efficiency limits its application. Hence, we upregulated A20 expression via transfection of rAd.ATF (recombinant adenovirus vector of artificial transcription factor) and rAd.A20 in rat carotid arteries after balloon dilatation (in vivo) and isolated VSMCs (in vitro)...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28911210/a20-an-essential-component-of-the-ubiquitin-editing-protein-complex-is-a-negative-regulator-of-inflammation-in-human-myometrium-and-foetal-membranes
#13
Martha Lappas
STUDY QUESTION: Does A20 regulate mediators involved in the terminal processes of human labour in primary myometrial and amnion cells? SUMMARY ANSWER: A20 is a nuclear factor-kappa B (NF-κB) responsive gene that acts as a negative regulator of NF-κB-induced expression of pro-labour mediators. WHAT IS KNOWN ALREADY: Inflammation is commonly implicated in spontaneous preterm birth and the processes involved in rupture of foetal membranes and uterine contractions...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28906466/therapeutic-effect-of-exogenous-truncated-ik-protein-in-inflammatory-arthritis
#14
Seulgi Choi, HyeLim Park, SeoYeon Jung, Eun-Kyung Kim, Mi-La Cho, Jun-Ki Min, Su-Jin Moon, Sang-Myeong Lee, Jang-Hee Cho, Dong-Hee Lee, Jae-Hwan Nam
Inhibitor K562 (IK) protein was first isolated from the culture medium of K562, a leukemia cell line. It is known to be an inhibitory regulator of interferon-γ-induced major histocompatibility complex class (MHC) II expression. Previously, we found that transgenic (Tg) mice constitutively expressing truncated IK (tIK) showed reduced numbers of pathogenic Th1 and Th17 cells, which are known to be involved in the development of rheumatoid arthritis (RA). Here, we investigated whether exogenous tIK protein has a therapeutic effect in arthritis in disease models and analyzed its mechanism...
September 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#15
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28901404/effects-of-anticholinergic-agent-on-mirna-profiles-and-transcriptomes-in-a-murine-model-of-allergic-rhinitis
#16
Minghua Hou, Wei Li, Zuozhong Xie, Jingang Ai, Bo Sun, Guolin Tan
Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28892081/a20-promotes-metastasis-of-aggressive-basal-like-breast-cancers-through-multi-monoubiquitylation-of%C3%A2-snail1
#17
Ji-Hyung Lee, Su Myung Jung, Kyung-Min Yang, Eunjin Bae, Sung Gwe Ahn, Jin Seok Park, Dongyeob Seo, Minbeom Kim, Jihoon Ha, Jaewon Lee, Jun-Hyeong Kim, Jun Hwan Kim, Akira Ooshima, Jinah Park, Donghyuk Shin, Youn Sook Lee, Sangho Lee, Geert van Loo, Joon Jeong, Seong-Jin Kim, Seok Hee Park
Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1...
October 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28878689/a20-tnfaip3-discriminates-tumor-necrosis-factor-tnf-induced-nf-%C3%AE%C2%BAb-from-jnk-pathway-activation-in-hepatocytes
#18
Federico Pinna, Michaela Bissinger, Katharina Beuke, Nicolas Huber, Thomas Longerich, Ursula Kummer, Peter Schirmacher, Sven Sahle, Kai Breuhahn
In the liver tumor necrosis factor (TNF)-induced signaling critically regulates the immune response of non-parenchymal cells as well as proliferation and apoptosis of hepatocytes via activation of the NF-κB and JNK pathways. Especially, the induction of negative feedback regulators, such as IκBα and A20 is responsible for the dynamic and time-restricted response of these important pathways. However, the precise mechanisms responsible for different TNF-induced phenotypes under physiological stimulation conditions are not completely understood so far...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28845260/a20%C3%A2-the-search-for-replication-competent-hiv-during-effective-therapy
#19
B Hiener, B Horsburgh, E Lee, S Palmer
No abstract text is available yet for this article.
March 2017: Virus Evolution
https://www.readbyqxmd.com/read/28842830/beneficial-effects-of-delayed-p7c3-a20-treatment-after-transient-mcao-in-rats
#20
Zachary B Loris, Justin R Hynton, Andrew A Pieper, W Dalton Dietrich
Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion after a 90-min middle cerebral artery occlusion (MCAO). In the present study, we investigated a more clinically relevant therapeutic window for P7C3-A20 treatment after ischemic stroke. MCAO rats were administered P7C3-A20 for 1 week, beginning immediately or at a delayed point, 6 h post-reperfusion...
August 25, 2017: Translational Stroke Research
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