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https://www.readbyqxmd.com/read/29471005/mir-155-5p-controls-colon-cancer-cell-migration-via-post-transcriptional-regulation-of-human-antigen-r-hur
#1
Amr Al-Haidari, Anwar Algaber, Raed Madhi, Ingvar Syk, Henrik Thorlacius
Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR...
February 19, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29470443/structure-antiplatelet-activity-relationships-of-novel-ruthenium-ii-complexes-investigation-of-its-molecular-targets
#2
Chih-Hsuan Hsia, Thanasekaran Jayakumar, Joen-Rong Sheu, Shin-Yi Tsao, Marappan Velusamy, Chih-Wei Hsia, Duen-Suey Chou, Chao-Chien Chang, Chi-Li Chung, Themmila Khamrang, Kao-Chang Lin
The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The present study aims to evaluate the structure-activity relationship (SAR) of newly synthesized ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR, and X-ray analyses were performed in this study...
February 22, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29464447/pathogenesis-of-skin-injury-of-systemic-lupus-erythematosus
#3
REVIEW
Guo-Min Deng
PURPOSE OF REVIEW: The second most common clinical expression in lupus patients is skin damage that the pathogenesis remains unclear. We discuss the role of pathological factors in the development of skin damage in SLE. RECENT FINDINGS: Skin deposited IgG is a crucial pathologic factor in the development of skin damage in SLE. Macrophages and signaling of TNFα/TNFR1 and IFN/IFNR play an important role in the skin injury of SLE. The intracellular molecules including Syk and calcium/calmodulin 4 and NFAT are involved in the manifestation of skin damage in lupus-prone mice...
February 21, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29459869/fc%C3%A2%C2%B5-receptor-promotes-the-survival-and-activation-of-marginal-zone-b-cells-and-protects-mice-against-bacterial-sepsis
#4
Jun Liu, Hanying Zhu, Jiawen Qian, Ermeng Xiong, Lumin Zhang, Yan-Qing Wang, Yiwei Chu, Hiromi Kubagawa, Takeshi Tsubata, Ji-Yang Wang
The marginal zone B cells (MZB) are located at the interface between the circulation and lymphoid tissue and as a gatekeeper play important roles in both innate and adaptive immune responses. We have previously found that MZB are significantly reduced in mice deficient in the IgM Fc receptor (FcμR) but how FcμR regulates the development and function of MZB remains unknown. In this study, we found that both marginal zone precursor (MZP) and MZB were decreased in FcμR -/- mice. The reduction of MZP and MZB was not due to impaired proliferation of these cells but rather due to their increased death...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449375/-novosphingobium-aromaticivorans-uses-a-nu-class-glutathione-s-transferase-as-a-glutathione-lyase-in-breaking-the-%C3%AE-aryl-ether-bond-of-lignin
#5
Wayne S Kontur, Craig A Bingman, Charles N Olmsted, Douglas R Wassarman, Arne Ulbrich, Daniel L Gall, Robert W Smith, Larissa M Yusko, Brian G Fox, Daniel R Noguera, Joshua J Coon, Timothy J Donohue
As a major component of plant cells walls, lignin is a potential renewable source of valuable chemicals. Several sphingomonad bacteria have been identified that can break the β-aryl ether bond connecting most phenylpropanoid units of the lignin heteropolymer. Here, we tested three sphingomonads predicted to be capable of breaking the β-aryl ether bond of the dimeric aromatic compound guaiacylglycerol-β-guaiacyl ether (GGE) and found that Novosphingobium aromaticivorans metabolizes GGE at one of the fastest rates thus far reported...
February 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29440271/phosphorylated-immunoreceptor-tyrosine-based-activation-motifs-and-integrin-cytoplasmic-domains-activate-spleen-tyrosine-kinase-via-distinct-mechanisms
#6
Lina Antenucci, Vesa P Hytönen, Jari Ylänne
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...
February 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29401630/tetrandrine-attenuates-the-bone-erosion-in-collagen-induced-arthritis-rats-by-inhibiting-osteoclastogenesis-via-spleen-tyrosine-kinase
#7
Yugai Jia, Yumeng Miao, Mengfan Yue, Mei Shu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro, tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes...
January 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29401256/syk-inhibition-blocks-proliferation-and-migration-of-glioma-cells-and-modifies-the-tumor-microenvironment
#8
Gerald Moncayo, Michal Grzmil, Tatiana Smirnova, Pawel Zmarz, Roland M Huber, Debby Hynx, Hubertus Kohler, Yuhua Wang, Hans-Rudolf Hotz, Nancy E Hynes, Georg Keller, Stephan Frank, Adrian Merlo, Brian A Hemmings
Background: Glioblastoma (GBM) is one of the most aggressive human brain tumors with a median survival of 15-18 months. There is a desperate need to find novel therapeutic targets. Various receptor protein kinases have been identified as potential targets; however, response rates in clinical studies have been somewhat disappointing. Targeting the Spleen Tyrosine Kinase (SYK), which acts downstream of a range of oncogenic receptors, may therefore show more promising results. Methods: Kinase expression of brain tumor samples including GBM and low-grade tumors were compared to normal brain and normal human astrocytes (NHA) by microarray analysis...
February 1, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29400702/integrin-cd11b-negatively-regulates-mincle-induced-signaling-via-the-lyn-sirp%C3%AE-shp1-complex
#9
Quanri Zhang, Wook-Bin Lee, Ji-Seon Kang, Lark Kyun Kim, Young-Joon Kim
During mycobacteria infection, anti-inflammatory responses allow the host to avoid tissue damage caused by overactivation of the immune system; however, little is known about the negative modulators that specifically control mycobacteria-induced immune responses. Here we demonstrate that integrin CD11b is a critical negative regulator of mycobacteria cord factor-induced macrophage-inducible C-type lectin (Mincle) signaling. CD11b deficiency resulted in hyperinflammation following mycobacterial infection. Activation of Mincle by mycobacterial components turns on not only the Syk signaling pathway but also CD11b signaling and induces formation of a Mincle-CD11b signaling complex...
February 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29386516/the-effect-of-pu-1-knockdown-on-gene-expression-and-function-of-mast-cells
#10
Yoshihito Oda, Kazumi Kasakura, Izumi Fujigaki, Azusa Kageyama, Ko Okumura, Hideoki Ogawa, Takuya Yashiro, Chiharu Nishiyama
PU.1 is a hematopoietic cell-specific transcription factor. In the current study, we investigated the role of PU.1 in the gene expression and the function of mouse mast cells (MCs) in vitro and in vivo. When PU.1 siRNA was introduced into bone marrow-derived MCs (BMMCs), IgE-mediated activation was reduced, and the Syk and FcεRIβ mRNA levels were significantly decreased. As the regulatory mechanism of the Syk gene is largely unknown, we performed promoter analysis and found that PU.1 transactivated the Syk promoter through direct binding to a cis-element in the 5'-untranslated region...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29386201/cd301b-mgl2-mononuclear-phagocytes-orchestrate-autoimmune-cardiac-valve-inflammation-and-fibrosis
#11
Lee A Meier, Jennifer L Auger, Brianna J Engelson, Hannah M Cowan, Elise R Breed, Mayra I Gonzalez-Torres, Joshua D Boyer, Mayank Verma, Aubyn Marath, Bryce A Binstadt
Background -Valvular heart disease (VHD) is common and affects the mitral valve (MV) most frequently. Despite the prevalence of mitral valve disease (MVD), the cellular and molecular pathways that initiate and perpetuate it are not well understood. Methods -K/B.g7 T cell receptor (TCR) transgenic mice spontaneously develop systemic autoantibody-associated autoimmunity, leading to fully-penetrant fibro-inflammatory MVD and arthritis. We used multiparameter flow cytometry, intracellular cytokine staining, and immunofluorescent staining to characterize the cells in inflamed K/B...
January 31, 2018: Circulation
https://www.readbyqxmd.com/read/29386115/cd209a-synergizes-with-dectin-2-and-mincle-to-drive-severe-th17-cell-mediated-schistosome-egg-induced-immunopathology
#12
Parisa Kalantari, Yoelkys Morales, Emily A Miller, Luis D Jaramillo, Holly E Ponichtera, Marcel A Wuethrich, Cheolho Cheong, Maria C Seminario, Joanne M Russo, Stephen C Bunnell, Miguel J Stadecker
The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle...
January 30, 2018: Cell Reports
https://www.readbyqxmd.com/read/29374031/bacterial-catabolism-of-%C3%AE-hydroxypropiovanillone-and-%C3%AE-hydroxypropiosyringone-produced-in-the-reductive-cleavage-of-arylglycerol-%C3%AE-aryl-ether-in-lignin
#13
Yudai Higuchi, Shogo Aoki, Hiroki Takenami, Naofumi Kamimura, Kenji Takahashi, Shojiro Hishiyama, Christopher S Lancefield, O Stephen Ojo, Yoshihiro Katayama, Nicholas J Westwood, Eiji Masai
Sphingobium sp. strain SYK-6 converts four stereoisomers of arylglycerol-β-guaiacyl ether into achiral β-hydroxypropiovanillone (HPV) via three stereospecific reaction steps. Here we determined the HPV catabolic pathway and characterized the HPV catabolic genes involved in the first two steps of the pathway. In SYK-6 cells, HPV was oxidized to vanilloyl acetic acid (VAA) via vanilloyl acetaldehyde (VAL). The resulting VAA was further converted into vanillate through the activation of VAA by coenzyme A. A syringyl-type HPV analog, β-hydroxypropiosyringone (HPS), was also catabolized via the same pathway...
January 26, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29372378/syk-targeted-dendritic-cell-mediated-cytotoxic-t-lymphocytes-enhance-the-effect-of-immunotherapy-on-retinoblastoma
#14
Xuemei Chen, Patricia Elena Kunda, Jianwei Lin, Meiling Zhou, Jinghan Huang, Huqin Zhang, Tao Liu
PURPOSE: Retinoblastoma (RB) is the most common primary intraocular tumor in children. Chemotherapy is currently the main method of RB treatment. Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in vitro cell immunotherapy to explore whether adoptive immunotherapy could be used as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK), which is significantly upregulated in RB cells and serves as a marker for RB cells. METHODS: Using lentiviruses, we genetically modified dendritic cells (DCs) to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs) in vitro...
January 25, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29371499/diversity-of-cell-wall-related-proteins-in-human-pathogenic-fungi
#15
Anna Muszewska, Sebastian Piłsyk, Urszula Perlińska-Lenart, Joanna S Kruszewska
The cell wall is one of the major keys to fungal identity. Fungi use their cell wall to sense the environment, and localize nutrients and competing microorganism. Pathogenic species additionally modify their cell walls to hide from a host's immune system. With the growing number of fungal infections and alarming shortage of available drugs, we are in need of new approaches to fight pathogens. The cell wall seems to be a natural target, since animal host cells are devoid of it. The current knowledge about fungal cell wall components is often limited, and there is huge diversity both in structure and composition between species...
December 29, 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/29355515/spliceosome-associated-protein-130-exacerbates-alcohol-induced-liver-injury-by-inducing-nlrp3-inflammasome-mediated-il1%C3%AE-in-mice
#16
Jong Won Kim, Yoon-Seok Roh, Hyeneui Jeong, Ho-Keun Yi, Min-Ho Lee, Chae Woong Lim, Bumseok Kim
Excessive alcohol consumption leads to chronic liver diseases. Macrophage-inducible C-type lectin (Mincle) is a C-type lectin receptor that recognizes spliceosome-associated protein 130 (SAP130) known as an endogenous ligand released from dying cells. Our aim was to examine the role of Mincle-SAP130 in the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was induced in wild-type (WT) and Mincle knout-out (KO) mice using a chronic-binge ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis, inflammation with neutrophil infiltration, and fibrosis compared to WT mice after alcohol feeding...
January 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29353412/helicobacter-pylori-lps-induced-gastric-mucosal-spleen-tyrosine-kinase-syk-recruitment-to-tlr4-and-activation-occurs-with-the-involvement-of-protein-kinase-c%C3%AE
#17
B L Slomiany, A Slomiany
Spleen tyrosine kinase (Syk) has emerged recently as a major effector of proinflammatory genes expression induced by LPS-elicited TLR4 activation, and manifested by the up-amplification in the production of inflammatory mediators, including PGE2 and NO. Here, we investigated the nature of factors involved in the recruitment and interaction of Syk with TLR4 in gastric mucosa in response to H. pylori LPS. We show that stimulation of gastric mucosal cells with the LPS leads to localization of Syk with the membrane-associated TLR4 complex and its activation through phosphorylation on Tyr...
January 20, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29342970/the-possible-importance-of-%C3%AE-3-integrins-for-leukemogenesis-and-chemoresistance-in-acute-myeloid-leukemia
#18
REVIEW
Silje Johansen, Annette K Brenner, Sushma Bartaula-Brevik, Håkon Reikvam, Øystein Bruserud
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342151/cd8-signaling-in-microglia-macrophage-m1-polarization-in-a-rat-model-of-cerebral-ischemia
#19
Jan Boddaert, Kenny Bielen, Bart 's Jongers, Ekta Manocha, Laetitia Yperzeele, Patrick Cras, Daniel Pirici, Samir Kumar-Singh
Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke...
2018: PloS One
https://www.readbyqxmd.com/read/29340070/a-novel-orally-available-syk-src-jak2-inhibitor-sklb-850-showed-potent-anti-tumor-activities-in-b-cell-lymphoma-bcl-models
#20
Nannan Zhang, Guo Zhang, Ning Liu, Wanting Lin, Sen Ji, Mingwu Zheng, Kai Chen, Xiao Liang, Guobo Li, Yu Ma, Jun Zhu, Ting Niu, Lin-Li Li, Jiong Li, Yu-Quan Wei, Sheng-Yong Yang
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells...
December 19, 2017: Oncotarget
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