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https://www.readbyqxmd.com/read/28239846/inhibition-of-6-phosphofructo-2-kinase-suppresses-fibroblast-like-synoviocytes-mediated-synovial-inflammation-and-joint-destruction-in-rheumatoid-arthritis
#1
Yaoyao Zou, Shan Zeng, Mingcheng Huang, Qian Qiu, Youjun Xiao, Maohua Shi, Zhongping Zhan, Liuqin Liang, Xiuyan Yang, Hanshi Xu
BACKGROUND AND PURPOSE: Abnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA. EXPERIMENTAL APPROACH: A specific PFKFB3 inhibitor, PFK15, and siRNA were used to evaluate the role of PFKFB3...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28239377/pro-inflammatory-signaling-in-a-3d-organotypic-skin-model-after-low-let-irradiation-nf-%C3%AE%C2%BAb-cox-2-activation-and-impact-on-cell-differentiation
#2
Anna Acheva, Giuseppe Schettino, Kevin M Prise
Nearly 85% of radiotherapy patients develop acute radiation dermatitis, which is an inflammatory reaction of the skin at the treatment field and in the surrounding area. The aims of this study were to unravel the mechanisms of radiation-induced inflammatory responses after localized irradiation in a human 3D organotypic skin culture model. This could provide possible inflammatory targets for reduction of skin side effects. 3D organotypic skin cultures were set up and locally irradiated with 225 kVp X-rays, using a combination of full exposure and partial shielding (50%) of the cultures...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#3
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28239159/sarsasapogenin-aa13-inhibits-lps-induced-inflammatory-responses-in-macrophage-cells-in-vitro-and-relieves-dimethylbenzene-induced-ear-edema-in-mice
#4
Dong Dong, Nan-Nan Zhou, Rui-Xuan Liu, Jia-Wei Xiong, Hui Pan, Si-Qi Sun, Lei Ma, Rui Wang
Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae. In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema. Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 μg/mL); pretreatment with AA13 (5-20 μmol/L) dose-dependently inhibited LPS-induced production of NO, TNF-α and PGE2, and LPS-stimulated expression levels of COX-2 and iNOS...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28238930/the-acute-exposure-of-tetrachloro-p-benzoquinone-a-k-a-chloranil-triggers-inflammation-and-neurological-dysfunction-via-toll-like-receptor-4-signaling-the-protective-role-of-melatonin-preconditioning
#5
Juanli Fu, Xiaomin Xia, Zixuan Liu, Yawen Wang, Yuxin Wang, Qiong Shi, Xiufang Song, Erqun Song, Yang Song
This study is aimed to investigate the inflammation and neurological dysfunction induced by tetrachloro-p-benzoquinone (TCBQ) through Toll-like receptor 4 (TLR4) signaling. We also investigated the protective role of melatonin as an antioxidant and anti-inflammatory agent. In vitro model was established by rat pheochromocytoma PC12 cells, meanwhile, TLR4 wild-type (C57BL/6) and knockout mice (C57BL/10ScNJ TLR4(-/-)) were used as in vivo model. In vitro study showed TCBQ exposure enhanced the expression of TLR4, myeloid differentiation factor 88 (MyD88) at both transcriptional and post-transcriptional levels...
February 23, 2017: Toxicology
https://www.readbyqxmd.com/read/28238855/mkp-1-negatively-regulates-lps-mediated-il-1%C3%AE-production-through-p38-activation-and-hif-1%C3%AE-expression
#6
Harvinder Talwar, Christian Bauerfeld, Mohamad Bouhamdan, Pershang Farshi, Yusen Liu, Lobelia Samavati
Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine that plays a major role in inflammatory diseases as well as cancer. The inflammatory response after Toll-like receptor (TLR) 4 activation is tightly regulated through phosphorylation of MAP kinases, including p38 and JNK pathways. The activation of MAP kinases is negatively regulated by MAPK phosphatases (MKPs). MKP-1 preferentially dephosphorylates p38 and JNK. IL-1β is regulated through the activation of MAPK, including p38 as well as several transcription factors...
February 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28238828/dilodendron-bipinnatum-radlk-inhibits-pro-inflammatory-mediators-through-the-induction-of-mkp-1-and-the-down-regulation-of-mapkp38-jnk-nf-%C3%AE%C2%BAb-pathways-and-cox-2-in-lps-activated-raw-264-7-cells
#7
Ruberlei Godinho de Oliveira, Geovane Roberto de Campos Castilho, André Luiz da Cunha, Fábio Miyajima, Domingos Tabajara de Oliveira Martins
ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Dilodendron bipinnatum Radlk. (Sapindaceae), a tree native to Pantanal of Mato Grosso, Brazil, popularly known as "mulher-pobre" (poor woman), has been historically used by the locals, after decoction and maceration, for the treatment of inflammatory conditions. We have recently shown that these preparations indeed possess anti-inflammatory properties, which are mediated by the inhibition of cell migration and the modulation of Th1 and Th2 cytokines...
February 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28237966/drosophila-model-of-myeloproliferative-neoplasm-reveals-a-feed-forward-loop-in-the-jak-pathway-mediated-by-p38-mapk-signalling
#8
Ana Terriente-Félix, Lidia Pérez, Sarah J Bray, Angel R Nebreda, Marco Milán
Myeloproliferative neoplasms (MPNs) of the Philadelphia-negative class comprise polycythemia vera, essential thrombocythemia and primary myelofibrosis (PMF). They are associated with aberrant amounts of myeloid lineage cells in the blood, and in the case of overt PMF, with the development of myelofibrosis in the bone marrow and the failure to produce normal blood cells. These diseases are usually caused by gain-of-function mutations in the kinase JAK2 Here we use Drosophila to investigate the consequences of activation of the JAK2 ortholog in hematopoiesis...
February 24, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28237815/antiepileptic-action-of-c-jun-n-terminal-kinase-jnk-inhibition-in-an-animal-model-of-temporal-lobe-epilepsy
#9
Tina Y Tai, Lindsay N Warner, Terrance D Jones, Sangwook Jung, Francis A Concepcion, David W Skyrud, Jason Fender, Yusha Liu, Aaron D Williams, John F Neumaier, Raimondo D'Ambrosio, Nicholas P Poolos
Several phosphorylation signaling pathways have been implicated in the pathogenesis of epilepsy arising from both genetic causes and acquired insults to the brain. Identification of dysfunctional signaling pathways in epilepsy may provide novel targets for antiepileptic therapies. We previously described a deficit in phosphorylation signaling mediated by p38 mitogen-activated protein kinase (p38 MAPK) that occurs in an animal model of temporal lobe epilepsy, and that produces neuronal hyperexcitability measured in vitro...
February 22, 2017: Neuroscience
https://www.readbyqxmd.com/read/28237619/glutamate-affects-the-production-of-epoxyeicosanoids-within-the-brain-the-up-regulation-of-brain-cyp2j-through-the-mapk-creb-signaling-pathway
#10
Mingzhou Liu, Quanfei Zhu, Jinhua Wu, Xuming Yu, Mingbai Hu, Xianfei Xie, Zheqiong Yang, Jing Yang, Yu-Qi Feng, Jiang Yue
Glutamate is the major excitatory neurotransmitter in the brain, and chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative diseases. We investigated the effects of glutamate at concentrations lower than the usual extrasynaptic concentrations on the production of epoxyeicosanoids mediated by brain CYP2J. Glutamate increased CYP2J2 mRNA levels in astrocytes in a dose-dependent manner, while an antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) attenuated the glutamate-induced increases in CYP2J2 levels by glutamate...
February 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28236306/p38-mitogen-activated-protein-kinase-regulates-mitochondrial-function-and-microvesicle-release-in-riboflavin-and-ultraviolet-light-treated-apheresis-platelet-concentrates
#11
Zhongming Chen, Peter Schubert, Sonia Bakkour, Brankica Culibrk, Michael P Busch, Dana V Devine
BACKGROUND: Biochemical analyses of mechanisms triggered in platelets (PLTs) upon pathogen inactivation (PI) are crucial to further understand the impact of PI on PLT functionality and, subsequently, quality. STUDY DESIGN AND METHODS: PLT concentrates (PCs) were split into four small illumination bags: 1) untreated control, 2) treated with riboflavin and ultraviolet light (RF/UV), and spiked with 3) solvent control dimethyl sulfoxide and 4) p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 before RF/UV treatment...
February 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28235675/il-15-stimulates-nkg2d-while-promoting-igm-expression-of-b-1a-cells
#12
Amlan Kanti Ghosh, Debolina Sinha, Ratna Biswas, Tapas Biswas
Interleukin (IL)-15, a key manipulator of T-cell function also modulates B-1a cell activity by augmenting activation markers, turning them towards type 1 polarization and immunoglobulin (Ig) expression which is significant in the context of gut immunity. Here we show, for the first time, IL-15 mediated up-regulation of the activation receptor NKG2D and its adaptor DAP10 in B-1a cells indicating their essential coupling with IL-15 receptor signaling pathway. Our results demonstrate IL-15 treatment increases phosphorylation of STAT5 and p38 leading to translocation of NF-κB onto the nucleus, an attribute that delineates activation of B-1a cells and its role in inflammation...
February 21, 2017: Cytokine
https://www.readbyqxmd.com/read/28235615/polysaccharide-purified-from-ganoderma-atrum-induced-activation-and-maturation-of-murine-myeloid-derived-dendritic-cells
#13
Hui Wang, Qiang Yu, Shao-Ping Nie, Quan-Dan Xiang, Ming-Ming Zhao, Shi-Yu Liu, Ming-Yong Xie, Shun-Qi Wang
Ganoderma atrum (G. atrum), a member of the genus Ganoderma, is an edible and medicinal fungus. In this study, we investigated the direct and indirect effects of G. atrum polysaccharide (PSG-1) on dendritic cells (DCs). Firstly, flow cytometric and ELISA analysis showed that PSG-1 increased cell surface molecule expression of MHC-II, CD80 and CD86, and enhanced the production of IL-12 p70, IL-6, IL-10, RANTES, MIP-1α and MCP-1 in DCs. PSG-1-treated DCs promoted the proliferation of splenic T lymphocyte of mouse in mixed lymphocyte reaction...
February 21, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28235485/modulation-of-autophagy-in-exjsrv-env-transfected-cells-through-the-akt-mtor-and-mapk-signaling-pathway
#14
Xiaolin Sun, Fangyuan Du, Shuying Liu
The envelope (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncoprotein of ovine pulmonary adenocarcinoma (OPA). Autophagy is involved in different cancers, but how it is carcinogenic in JSRV Env is unclear. Modulation of autophagy in exJSRV-env-NM-transfected cells through the Akt/mTOR and MAPK signaling pathway was studied, and we observed strong positive labeling of p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-p38 and p-JNK in tumor cells and typical type II pneumocytes in naturally infected OPA lung tissues, which was co-aligned with JSRV-Env positive cells as shown by immunohistochemical and microscopic analysis...
February 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28235426/antiproliferative-activity-and-apoptosis-induction-by-3-4-dibenzyloxyflavonol-on-human-leukemia-cells
#15
Mercedes Said, Ignacio Brouard, José Quintana, Francisco Estévez
In this study, we investigated the effects of synthetic 3',4'-dibenzyloxyflavonol on viabilities of eight human tumor cells. It was cytotoxic against leukemia cells (HL-60, U-937, MOLT-3, K-562, NALM-6, Raji), with significant effects against P-glycoprotein-overexpressing K-562/ADR and Bcl-2-overexpressing U-937/Bcl-2 cells, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. The IC50 value for the leukemia HL-60 cells was 0.8 ± 0.1 μM...
February 21, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28230167/cytotrophoblast-not-syncytiotrophoblast-dominates-glycolysis-and-oxidative-phosphorylation-in-human-term-placenta
#16
Kevin S Kolahi, Amy M Valent, Kent L Thornburg
The syncytiotrophoblast (SCT) at the maternal-fetal interface has been presumed to be the primary driver of placental metabolism, and the underlying progenitor cytotrophoblast cells (CTB) an insignificant contributor to placental metabolic activity. However, we now show that the metabolic rate of CTB is much greater than the SCT. The oxygen consumption and extracellular acidification rate, a measure of glycolysis, are both greater in CTB than in SCT in vitro (CTB: 96 ± 16 vs SCT: 46 ± 14 pmol O2 × min(-1) × 100 ng DNA(-1), p < 0...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229590/impacts-of-crosslinkers-on-biological-effects-of-mesoporous-silica-nanoparticles
#17
Yi-Ping Chen, Si-Han Wu, I-Chih Chen, Chien-Tsu Chen
Chemically synthesized crosslinkers play decisive roles in variable cargos attached to nanoparticles (NPs). Previous studies reported that surface properties, such as the size, charge, and surface chemistry, are particularly important determinants influencing the biological fate and actions of NPs and cells. Recent studies also focused on the relationship of serum proteins with the surface properties of NPs (also called the protein corona), which is recognized as a key factor in determining the cytotoxicity and biodistribution...
February 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28228365/isoquinoline-alkaloids-from-coptis-japonica-stimulate-the-myoblast-differentiation-via-p38-map-kinase-and-akt-signaling-pathway
#18
Heyjin Lee, Le Thi Tuong, Ji Hye Jeong, Sang-Jin Lee, Gyu-Un Bae, Jae-Ha Ryu
To overcome the muscle atrophy, such as cachexia and sarcopenia, we tried to find myogenic agents from medicinal plants. From myogenic extract of Coptis japonica, we purified six isoquinoline alkaloids and evaluated their effects on transactivation of myoD and MHC expression in C2C12 cells during differentiation process. Among obtained compounds, magnoflorine most efficiently enhanced the myoblast differentiation by activating the p38 MAP kinase and Akt pathway, and also increased the number of multinucleated and cylinder-shaped myotubes...
February 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28228072/curcumin-and-endothelial-function-evidence-and-mechanisms-of-protective-effects
#19
Maryam Saberi Karimian, Matteo Pirro, Thomas P Johnston, Muhammed Majeed, Amirhossein Sahebkar
BACKGROUND: The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by non-invasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions...
February 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28225870/pdk2-promotes-chondrogenic-differentiation-of-mesenchymal-stem-cells-by-upregulation-of-sox6-and-activation-of-jnk-mapk-erk-pathway
#20
H Wang, X B Shan, Y J Qiao
This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR)...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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