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https://www.readbyqxmd.com/read/29148537/adenomatoid-tumors-of-the-male-and-female-genital-tract-are-defined-by-traf7-mutations-that-drive-aberrant-nf-kb-pathway-activation
#1
Benjamin Goode, Nancy M Joseph, Meredith Stevers, Jessica Van Ziffle, Courtney Onodera, Eric Talevich, James P Grenert, Iwei Yeh, Boris C Bastian, Joanna J Phillips, Karuna Garg, Joseph T Rabban, Charles Zaloudek, David A Solomon
Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#2
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29146721/development-of-a-function-blocking-antibody-against-fibulin-3-as-targeted-reagent-for-glioblastoma
#3
Mohan Sobhana Nandhu, Prajna Behera, Vivek Bhaskaran, Sharon L Longo, Lina M Barrera-Arenas, Sadhak Sengupta, Diego J Rodriguez-Gil, E Antonio Chiocca, Mariano S Viapiano
PURPOSE: We sought a novel approach against glioblastomas (GBM) focused on targeting signaling molecules localized in the tumor extracellular matrix (ECM). We investigated fibulin-3, a glycoprotein that forms the ECM scaffold of GBMs and promotes tumor progression by driving Notch and NF-kB signaling. EXPERIMENTAL DESIGN: We used deletion constructs to identify a key signaling motif of fibulin-3. A monoclonal antibody (mAb428.2) was generated against this epitope and extensively validated for specific detection of human fibulin-3...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29142196/dj-1-controls-bone-homeostasis-through-the-regulation-of-osteoclast-differentiation
#4
Hyuk Soon Kim, Seung Taek Nam, Se Hwan Mun, Sun-Kyeong Lee, Hyun Woo Kim, Young Hwan Park, Bokyung Kim, Kyung-Jong Won, Hae-Rim Kim, Yeong-Min Park, Hyung Sik Kim, Michael A Beaven, Young Mi Kim, Wahn Soo Choi
Receptor activator of NF-kB ligand (RANKL) generates intracellular reactive oxygen species (ROS), which increase RANKL-mediated signaling in osteoclast (OC) precursor bone marrow macrophages (BMMs). Here we show that a ROS scavenging protein DJ-1 negatively regulates RANKL-driven OC differentiation, also called osteoclastogenesis. DJ-1 ablation in mice leads to a decreased bone volume and an increase in OC numbers. In vitro, the activation of RANK-dependent signals is enhanced in DJ-1-deficient BMMs as compared to wild-type BMMs...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#5
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29137729/the-shear-wave-elastic-modulus-and-the-increased-nuclear-factor-kappa-b-nf-kb-p65-and-cyclooxygenase-2-cox-2-expression-in-the-area-of-myofascial-trigger-points-activated-in-a-rat-model-by-blunt-trauma-to-the-vastus-medialis
#6
Hengyong Lv, Zhen Li, Tiantian Hu, Yuexiang Wang, Jinpeng Wu, Yingxin Li
We aimed to elucidate the increased inflammatory cytokines expression such as nuclear factor kappa B (NF-kB/p65), cyclooxygenase-2 (COX-2), and voltage-gated calcium channels (VGCC) in the area of activated myofascial trigger points (MTrPs) in a rat model by blunt trauma to the vastus medialis and to evaluate the feasibility of a quantitative analysis of muscle elastic modulus using shear wave elastography (SWE). Twelve 7-week-old male SD rats were divided into normal (NM, n = 6) and model groups (MO, n = 6)...
November 6, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/29137315/protective-effects-of-sulforaphane-on-di-n-butylphthalate-induced-testicular-oxidative-stress-injury-in-male-mice-offsprings-via-activating-nrf2-are-pathway
#7
Zhiqiang Qin, Jingyuan Tang, Peng Han, Xuping Jiang, Chengdi Yang, Ran Li, Min Tang, Baixin Shen, Wei Wang, Chao Qin, Wei Zhang
Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2(+/+)) and Nrf2-deficient (Nrf2(-/-)) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133857/pdgfr-modulated-mir-23b-cluster-and-mir-125a-5p-suppress-lung-tumorigenesis-by-targeting-multiple-components-of-kras-and-nf-kb-pathways
#8
Srivatsava Naidu, Lei Shi, Peter Magee, Justin D Middleton, Alessandro Laganá, Sudhakar Sahoo, Hui Sun Leong, Melanie Galvin, Kristopher Frese, Caroline Dive, Vincenza Guzzardo, Matteo Fassan, Michela Garofalo
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132130/effect-of-huagantongluofang-a-chinese-traditional-medicine-in-hepatic-fibrogenesis-in-a-mouse-model-of-biliary-cirrhosis
#9
Ji Xuan, Wei Wen, Yong Wang, Feng Wang, Hua-Bing Xu, Mei Shao, Ya Yang, Yao-Zhou Tian
BACKGROUND: Biliary cirrhosis (BC) is a chronic cholestatic liver disease, in which hepatic fibrosis is an early symptom. This study aimed to identify the biological function and the therapeutic effect of a Chinese traditional medicine, HuaGanTongLuoFang (HGTLF), in a mouse model of BC. METHODS: The mice (n = 72) were randomly divided into a sham group (n =12) and BC group (n = 60). The animals in the BC group were then randomly divided into five groups (n = 12 in each) and treated with three different doses of HGTLF, ureodeoxycholic acid (UDCA), or normal saline (the model group)...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131265/metformin-reduces-satb2-mediated-osteosarcoma-stem-cell-like-phenotype-and-tumor-growth-via-inhibition-of-n-cadherin-nf-kb-signaling
#10
H Y Xu, W Fang, Z W Huang, J C Lu, Y Q Wang, Q L Tang, G H Song, Y Kang, X J Zhu, C Y Zou, H L Yang, J N Shen, J Wang
OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma. MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29131009/effects-of-microrna-499-on-the-inflammatory-damage-of-endothelial-cells-during-coronary-artery-disease-via-the-targeting-of-pdcd4-through-the-nf-%C3%AE-%C3%AE-tnf-%C3%AE-signaling-pathway
#11
Yu-Hong Zhang, Keng He, Gang Shi
BACKGROUND/AIMS: This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. METHODS: A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29126910/impaired-oligodendrogenesis-and-myelination-by-elevated-s100b-levels-during-neurodevelopment
#12
Gisela Santos, Andreia Barateiro, Cláudio M Gomes, Dora Brites, Adelaide Fernandes
High levels of the inflammatory molecule S100B protein have been identified in sera from several perinatal inflammatory conditions involving myelin damage and associated with an adverse prognosis or the emergence of sequelea. S100B is essential for oligodendrocyte (OL) differentiation and maturation, but it remains to be established if excessive levels of released S100B upon early brain injury are deleterious in the neurodevelopmental period. Here, we investigated this possibility by evaluating how elevated S100B affects oligodendrogenesis during this period...
November 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29118926/gts-21-attenuates-lps-induced-renal-injury-via-the-cholinergic-anti-inflammatory-pathway-in-mice
#13
Yang Gao, Kai Kang, Haitao Liu, Weilan Kong, Qiuyuan Han, Xing Zhang, Rui Huang, Jingdong Qu, Hongliang Wang, Sicong Wang, Ruijin Liu, Yansong Liu, Kaijiang Yu
This study aimed to investigate the role of GTS-21 in cholinergic anti-inflammatory pathway-mediated protection of LPS-induced septic renal injury in mice. C57BL/6 mice were used to construct septic injury models. The optimal duration of lipopolysaccharide (LPS) treatment was determined using HE staining and TUNEL assay. Mice injected with saline were used as blank control and with LPS (10 mg/kg) as model, which were further treated with α-bungarotoxin (BT-LPS), GTS-21 (GTS-21-LPS) and BT and GTS-21 (BT-GTS-21-LPS)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29117939/novel-signaling-complex-between-troy-and-egfr-mediates-glioblastoma-cell-invasion
#14
Zonghui Ding, Alison Roos, Jean Kloss, Harshil Dhruv, Sen Peng, Patrick Pirrotte, Jennifer M Eschbacher, Nhan L Tran, Joseph C Loftus
Glioblastoma is the most frequent primary brain tumor in adults and a highly lethal malignancy with a median survival of about 15 months. The aggressive invasion of the surrounding normal brain makes complete surgical resection impossible, increases the resistance to radiation and chemotherapy, and assures tumor recurrence. Thus, there is an urgent need to develop innovative therapeutics to target the invasive tumor cells for improved treatment outcomes of this disease. Expression of TROY (TNFRSF19), a member of the tumor necrosis factor (TNF) receptor family, increases with increasing glial tumor grade and inversely correlates with patient survival...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29116065/-immunogenicity-of-recombinant-analog-of-antitumor-protein-lactaptin
#15
A V Tkachenko, O S Troitskaya, D V Semenov, E V Dmitrienko, E V Kuligina, V A Richter, O A Koval
Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29115856/lps-induced-acute-lung-injury-involves-the-nf-%C3%AE%C2%BAb-mediated-downregulation-of-sox18
#16
Christine M Gross, Manuela Kellner, Ting Wang, Qing Lu, Xutong Sun, Evgeny A Zemskov, Satish Noonepalle, Archana Kangath, Sanjiv Kumar, Manuel Gonzalez-Garay, Ankit A Desai, Saurabh Aggarwal, Boris Gorshkov, Christina Klinger, Alexander D Verin, John D Catravas, Jeffrey R Jacobson, Jason X-J Yuan, Ruslan Rafikov, Joe G N Garcia, Stephen M Black
One of the early events in the progression of lipopolysaccharide (LPS)-mediated acute lung injury (ALI) in mice is the disruption of the pulmonary endothelial barrier resulting in lung edema. However, the molecular mechanisms by which the endothelial barrier becomes compromised remain unresolved. The SRY-related High Mobility Group box (Sox) group-F family member, Sox18, is a barrier- protective protein through its ability to increase the expression of the tight junction protein, Claudin-5. Thus, the purpose of this study was to determine if down-regulation of the Sox18-Claudin-5 axis plays a role in the pulmonary endothelial barrier disruption associated with LPS exposure...
November 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29115665/effects-of-xist-mir-137-axis-on-neuropathic-pain-by-targeting-tnfaip1-in-a-rat-model
#17
Ying Zhao, Sen Li, Min Xiao, Yan Shi, Chang-Ming Zhao
Non-coding RNAs have been reported to participate in the pathophysiology of neuropathic pain. The objective of our study was to investigate the biological role of XIST in neuropathic pain development. In our study, we identify and validate that lncRNA XIST was markedly increased and miR-137 was significantly decreased in chronic constriction injury (CCI) rats. XIST silencing alleviated pain behaviors including both mechanical and thermal hyperalgesia in the CCI rats. XIST was predicted to interact with miR-137 by bioinformatics technology and dual-luciferase reporter assays confirmed the correlation between XIST and miR-137...
November 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29115455/dioscin-inhibits-ischemic-stroke%C3%A2-induced-inflammation-through-inhibition-of-the-tlr4-myd88-nf%C3%A2-%C3%AE%C2%BAb-signaling-pathway-in-a-rat-model
#18
Shilin Zhu, Siyuan Tang, Feng Su
Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, anti‑inflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase‑3 and caspase‑9 activity was analyzed using Caspase‑3 and caspase‑9 activity kits...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29112935/histone-deacetylase-6-inhibitor-acy-1215-protects-against-experimental-acute-liver-failure-by-regulating-the-tlr4-mapk-nf-%C3%AE%C2%BAb-pathway
#19
Wen-Bin Zhang, Hai-Yue Zhang, Fang-Zhou Jiao, Lu-Wen Wang, Hong Zhang, Zuo-Jiong Gong
Histone deacetylase 6 (HDAC6) is considered a new target for anticancer, anti-inflammatory, and neurodegenerative treatment. ACY-1215 is a selective histone deacetylase 6 inhibitor, and it has been recognized as a potential anticancer and anti-inflammation drug. The aim of our study was to investigate whether ACY-1215 has protective effects on acute liver failure (ALF) in mice and explore its potential mechanism. Male C57/BL6 mice were divided into normal, model, and ACY-1215 groups. ACY-1215 (25mg/kg) and same amounts of saline were given to mice...
November 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29110956/activation-inhibitors-of-nuclear-factor-kappa-b-protect-neurons-against-the-nmda-induced-damage-in-the-rat-retina
#20
Kenji Sakamoto, Tatsuya Okuwaki, Hiroko Ushikubo, Asami Mori, Tsutomu Nakahara, Kunio Ishii
We reported that high-mobility group Box-1 (HMGB1) was involved in excitoneurotoxicity in the retina. HMGB1 is known to activate nuclear factor kappa B (NF-κB). However, the role of NF-κB in excitotoxicity is still controversial. Here, we demonstrated that NF-κB activation induced by NMDA led to the retinal neurotoxicity. Male Sprague-Dawley rats were used, and NMDA (200 nmol/eye) and bovine HMGB1 (15 μg/eye) were intravitreally injected. Triptolide (500 pmol/eye), BAY 11-7082 (500 pmol/eye), and IMD-0354 (7...
September 29, 2017: Journal of Pharmacological Sciences
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