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https://www.readbyqxmd.com/read/28817116/total-tanshinones-exhibits-anti-inflammatory-effects-through-blocking-tlr4-dimerization-via-the-myd88-pathway
#1
Hongwei Gao, Xin Liu, Wen Sun, Naixin Kang, Yanli Liu, Shilin Yang, Qiong-Ming Xu, Chunming Wang, Xiuping Chen
Tanshinones belong to a group of lipophilic constituents of Salvia miltiorrhiza Bunge (Danshen), which is widely used in traditional Chinese medicine. A deluge of studies demonstrated that tanshinones exert anti-inflammatory effects, but the underlying mechanisms remain unclear to date. This study investigated the anti-inflammatory effects and mechanisms of total tanshinones (TTN). TTN suppressed the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the secretion of TNF-α, IL-6, and IL-1β in RAW264...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28811826/anti-inflammatory-effect-of-piper-attenuatum-methanol-extract-in-lps-stimulated-inflammatory-responses
#2
You Jin Kim, Jeong Deok, Sunggyu Kim, Deok Hyo Yoon, Gi-Ho Sung, Adithan Aravinthan, Seungihm Lee, Mi-Nam Lee, Suntaek Hong, Jong-Hoon Kim, Young-Jin Son, Jae Youl Cho
Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#3
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811301/topically-applied-carvedilol-attenuates-solar-ultraviolet-radiation-induced-skin-carcinogenesis
#4
Kevin M Huang, Sherry Liang, Steven Yeung, Etuajie Oiyemhonlan, Kristan H Cleveland, Cyrus Parsa, Robert Orlando, Frank L Meyskens, Bradley Andresen, Ying Huang
In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P+ cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol on UV-induced neoplastic transformation...
August 15, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28807774/chlorin-e6-mediated-photodynamic-therapy-promotes-collagen-production-and-suppresses-mmps-expression-via-modulating-ap-1-signaling-in-p-acnes-stimulated-hacat-cells
#5
A-Reum Ryu, Mi-Young Lee
BACKGROUND: Photodynamic therapy (PDT) is a clinically approved therapeutics for cancers and non-neoplastic diseases, based on the use of a photosensitizer activated by a light. The feasibility of PDT depends on several factors, such as PDT dose, photosensitizer efficacy, type of light source, and target tissue irradiated. METHODS: In this study, the second generation photosensitizer chlorin e6 (Ce6) and halogen light were used to investigate their PDT effect on the collagen production and MMPs expression of heat killed P...
August 11, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28805801/small-molecule-studies-identify-cdk8-as-a-regulator-of-il-10-in-myeloid-cells
#6
Liv Johannessen, Thomas B Sundberg, Daniel J O'Connell, Raivo Kolde, James Berstler, Katelyn J Billings, Bernard Khor, Brinton Seashore-Ludlow, Anne Fassl, Caitlin N Russell, Isabel J Latorre, Baishan Jiang, Daniel B Graham, Jose R Perez, Piotr Sicinski, Andrew J Phillips, Stuart L Schreiber, Nathanael S Gray, Alykhan F Shamji, Ramnik J Xavier
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation...
August 14, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28801231/anti-inflammatory-chromatinscape-suggests-alternative-mechanisms-of-glucocorticoid-receptor-action
#7
Kyu-Seon Oh, Heta Patel, Rachel A Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D C Fraser, Gordon L Hager, Myong-Hee Sung
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS)...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28798381/transcriptional-hallmarks-of-cancer-cell-lines-reveal-an-emerging-role-of-branched-chain-amino-acid-catabolism
#8
Ieva Antanavičiūtė, Valeryia Mikalayeva, Ieva Ceslevičienė, Gintarė Milašiūtė, Vytenis Arvydas Skeberdis, Sergio Bordel
A comparative analysis between cancer cell lines and healthy dividing cells was performed using data (289 microarrays and 50 RNA-seq samples) from 100 different cancer cell lines and 6 types of healthy stem cells. The analysis revealed two large-scale transcriptional events that characterize cancer cell lines. The first event was a large-scale up-regulation pattern associated to epithelial-mesenchymal transition, putatively driven by the interplay of the SP1 transcription factor and the canonical Wnt signaling pathway; the second event was the failure to overexpress a diverse set of genes coding membrane and extracellular proteins...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794385/association-between-a-ccl17-genetic-variant-and-risk-of-coronary-artery-disease-in-a-chinese-han-population
#9
Yicong Ye, Xinglin Yang, Bo Long, Haiyu Pang, Yicheng Zhu, Shuyang Zhang
BACKGROUND: In the present study we investigated the effects of genetic variations in the C-C motif chemokine ligand 17 (CCL17) gene on serum CCL17 levels and risk of coronary artery disease (CAD).Methods and Results:A case-control study was conducted to determine causal inferences amongCCL17single-nucleotide polymorphisms (SNPs), serum CCL17 levels, and risk of CAD. Luciferase assays, electrophoretic mobility shift assays (EMSA), and allele-specific quantitative chromatin immunoprecipitation (ChIP) assays were used to assess the function of the SNPs...
August 8, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#10
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28782589/the-role-of-thioredoxin-1-in-resisting-methamphetamine-induced-rewarding-effect
#11
Mengbing Huang, Lingpin Kong, Lihua Yang, Xiang Li, Xiaoshuang Zhou, Ye Li, Jie Bai
Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays role in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice...
August 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28777797/alteration-of-wnt5a-expression-and-of-the-non-canonical-wnt-pcp-and-wnt-pkc-ca2-pathways-in-human-osteoarthritis-osteoblasts
#12
Xavier Martineau, Élie Abed, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Daniel Lajeunesse
OBJECTIVE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/β-catenin signaling pathway (cWnt), and a reduced mineralization in vitro. In addition to the cWnt pathway, at least two non-canonical signaling pathways, the Wnt/PKC and Wnt/PCP pathway have been described...
2017: PloS One
https://www.readbyqxmd.com/read/28776955/antineoplastic-effects-of-histone-deacetylase-inhibitors-in-neuroendocrine-cancer-cells-are-mediated-through-transcriptional-regulation-of-notch1-by-activator-protein-1
#13
Samuel Jang, Haining Jin, Madhuchhanda Roy, Alice L Ma, Shaoqin Gong, Renata Jaskula-Sztul, Herbert Chen
Notch signaling is minimally active in neuroendocrine (NE) cancer cells. While histone deacetylase inhibitors (HDACi) suppress NE cancer growth by inducing Notch, the molecular mechanism underlying this interplay has not yet been defined. NE cancer cell lines BON, H727, and MZ-CRC-1 were treated with known HDACi Thailadepsin-A (TDP-A) and valproic acid (VPA), and Notch1 mRNA expression was measured with RT-PCR. Truncated genomic fragments of the Notch1 promotor region fused with luciferase reporter were used to identify the potential transcription factor (TF) binding site...
August 4, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28769048/in-vivo-monitoring-of-the-recruitment-and-activation-of-ap-1-by-arf1
#14
Etienne Sauvageau, Peter J McCormick, Stephane Lefrancois
AP-1 is a clathrin adaptor recruited to the trans-Golgi Network where it can interact with specific signals found in the cytosolic tail of cargo proteins to incorporate them into clathrin-coated vesicles for trafficking. The small G protein Arf1 regulates the spatiotemporal recruitment of AP-1 and also drives a conformational change favoring an interaction with cargo proteins. A recent crystal structure and in vitro experiments highlighted potential residues mediating the AP-1/Arf1 interaction and the unlocking of the complex...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765265/is-myometrial-inflammation-a-cause-or-a-consequence-of-term-human-labour
#15
Natasha Singh, Bronwen Herbert, Gavin Sooranna, Nic Orsi, Lydia Edey, Tathagata Dasgupta, S R Sooranna, Steve Yellon, M R Johnson
Myometrial inflammation is thought to have a pivotal role in the onset of term and some forms of preterm labour. This is based on the comparison of samples taken from women undergoing term elective CS prior to the onset of labour with those taken from women in established labour. Consequently, it is not clear whether myometrial inflammation is a cause or a consequence of labour. Our objective is to test the hypothesis that myometrial inflammation is a consequence of the onset of labour. To test this hypothesis we have obtained myometrial samples from women at various stages of pregnancy and spontaneous labour and studied the activation of the AP-1 (c-Jun) and NFκB (p65) systems, cytokine mRNA expression and protein levels and inflammatory cell infiltration and activation...
August 1, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28760770/transcriptional-mechanisms-that-control-expression-of-the-macrophage-colony-stimulating-factor-receptor-locus
#16
REVIEW
Rocio Rojo, Clare Pridans, David Langlais, David A Hume
The proliferation, differentiation, and survival of cells of the macrophage lineage depends upon signals from the macrophage colony-stimulating factor (CSF) receptor (CSF1R). CSF1R is expressed by embryonic macrophages and induced early in adult hematopoiesis, upon commitment of multipotent progenitors to the myeloid lineage. Transcriptional activation of CSF1R requires interaction between members of the E26 transformation-specific family of transcription factors (Ets) (notably PU.1), C/EBP, RUNX, AP-1/ATF, interferon regulatory factor (IRF), STAT, KLF, REL, FUS/TLS (fused in sarcoma/ranslocated in liposarcoma) families, and conserved regulatory elements within the mouse and human CSF1R locus...
August 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28759609/knockout-of-the-gamma-subunit-of-the-ap-1-adaptor-complex-in-the-human-parasite-trypanosoma-cruzi-impairs-infectivity-and-differentiation-and-prevents-the-maturation-and-targeting-of-the-major-protease-cruzipain
#17
Claudia Maria do Nascimento Moreira, Cassiano Martin Batista, Jessica Chimenes Fernandes, Rafael Luis Kessler, Maurilio José Soares, Stenio Perdigão Fragoso
The AP-1 Adaptor Complex assists clathrin-coated vesicle assembly in the trans-Golgi network (TGN) of eukaryotic cells. However, the role of AP-1 in the protozoan Trypanosoma cruzi-the Chagas disease parasite-has not been addressed. Here, we studied the function and localization of AP-1 in different T. cruzi life cycle forms, by generating a gene knockout of the large AP-1 subunit gamma adaptin (TcAP1-γ), and raising a monoclonal antibody against TcAP1-γ. Co-localization with a Golgi marker and with the clathrin light chain showed that TcAP1-γ is located in the Golgi, and it may interact with clathrin in vivo, at the TGN...
2017: PloS One
https://www.readbyqxmd.com/read/28757135/synergism-between-thioredoxin-reductase-inhibitor-ethaselen-and-sodium-selenite-in-inhibiting-proliferation-and-inducing-death-of-human-non-small-cell-lung-cancer-cells
#18
Xiaoqing Zheng, Wei Xu, Ruoxuan Sun, Hanwei Yin, Chaoran Dong, Huihui Zeng
New effective treatment for human non-small cell lung cancer (NSCLC) is needed. The thioredoxin (Trx) system composes of thioredoxin reductase (TrxR), Trx and NADPH. In this study, we combined an organic selenium compound--TrxR inhibitor ethaselen (BBSKE) with low dosage sodium selenite to inhibit proliferation and induce death of NSCLC cells, and identified underlying mechanisms. Synergistic anti-proliferation effect of BBSKE and selenite was found in human NSCLC cell lines, A549, NCI-H1299 and NCI-1266. A significant increase of apoptosis, necrosis and autophagy were observed in the group of BBSKE plus selenite in A549 cells...
July 27, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28753655/bacterial-effector-nlel-promotes-enterohemorrhagic-e-coli-induced-attaching-and-effacing-lesions-by-ubiquitylating-and-inactivating-jnk
#19
Xiangpeng Sheng, Qing You, Hongnian Zhu, ZeNan Chang, Qingrun Li, Haifeng Wang, Chen Wang, Hongyan Wang, Lijian Hui, Chongtao Du, Xiaoduo Xie, Rong Zeng, Anning Lin, Dongfang Shi, Kangcheng Ruan, Jinghua Yan, George Fu Gao, Feng Shao, Ronggui Hu
As a major diarrheagenic human pathogen, enterohemorrhagic Escherichia coli (EHEC) produce attaching and effacing (A/E) lesions, characterized by the formation of actin pedestals, on mammalian cells. A bacterial T3SS effector NleL from EHEC O157:H7 was recently shown to be a HECT-like E3 ligase in vitro, but its biological functions and host targets remain elusive. Here, we report that NleL is required to effectively promote EHEC-induced A/E lesions and bacterial infection. Furthermore, human c-Jun NH2-terminal kinases (JNKs) were identified as primary substrates of NleL...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28751006/apolipoprotein-e-promotes-invasion-in-oral-squamous-cell-carcinoma
#20
Sangeeta K Jayakar, Olivier Loudig, Margaret Brandwein-Gensler, Ryung S Kim, Thomas J Ow, Berrin Ustun, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall, Thomas J Belbin
Oral squamous cell carcinoma (OSCC) patients generally have a poor prognosis, due to the invasive nature of these tumors. In comparing transcription profiles between OSCC tumors with a more invasive (WPOI 5) versus a less invasive (WPOI 3) pattern of invasion, we identified a total of 97 genes that were overexpressed at least 1.5-fold in the more invasive tumor subtype. The most functionally relevant genes were assessed using in vitro invasion assays with an OSCC cell line (UM-SCC-1). Individual siRNA knockdown of 15 of these 45 genes resulted in significant reductions in tumor cell invasion compared to a non-targeting siRNA control...
July 24, 2017: American Journal of Pathology
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