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https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#1
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28103916/tim-1-defines-a-human-regulatory-b-cell-population-that-is-altered-in-frequency-and-function-in-systemic-sclerosis-patients
#2
Octavio Aravena, Ashley Ferrier, Madhvi Menon, Claudia Mauri, Juan Carlos Aguillón, Lilian Soto, Diego Catalán
BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive production of extracellular matrix by fibroblasts on skin and internal organs. Although Th2 cells have been involved in fibroblast stimulation, hyperactivated B cells may also play an important role. Regulatory B cells (Bregs) are cells capable of inhibiting inflammatory responses and controlling autoimmune diseases. Although many Breg populations have in common the ability to produce high amounts of IL-10, a unique surface marker defining most human Bregs is lacking...
January 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28103692/phenotypic-screen-for-cardiac-regeneration-identifies-molecules-with-differential-activity-in-human-epicardium-derived-cells-versus-cardiac-fibroblasts
#3
Amalia I Paunovic, Lauren Drowley, Anneli Nordqvist, Elke Ericson, Elizabeth Mouchet, Anna Jonebring, Gunnar Grönberg, Alexander J Kvist, Ola Engkvist, Martin R Brown, Karin Gedda, Marie-José Goumans, Qing-Dong Wang, Alleyn T Plowright
Activation and proliferation of resident cardiac progenitor cells has therapeutic potential to repair the heart after injury. However, research has been impeded by a lack of well-defined and characterized cell sources and difficulties in translation to screening platforms. Here, we describe the development, validation, and use of a 384-well phenotypic assay in primary human epicardium-derived cells (EPDCs) to identify compounds that induce proliferation while maintaining the progenitor phenotype. Using this assay, we screened 7400 structurally diverse compounds where greater than 90% are biologically annotated and known to modulate a broad range of biological targets...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103571/identification-of-aurintricarboxylic-acid-as-a-selective-inhibitor-of-the-tweak-fn14-signaling-pathway-in-glioblastoma-cells
#4
Alison Roos, Harshil D Dhruv, Ian T Mathews, Landon J Inge, Serdar Tuncali, Lauren K Hartman, Donald Chow, Nghia Millard, Holly H Yin, Jean Kloss, Joseph C Loftus, Jeffrey A Winkles, Michael E Berens, Nhan L Tran
The survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102843/il-17-mediated-mitochondrial-dysfunction-impairs-apoptosis-in-rheumatoid-arthritis-synovial-fibroblasts-through-activation-of-autophagy
#5
Eun Kyung Kim, Jeong-Eun Kwon, Seon-Young Lee, Eun-Jung Lee, Da Som Kim, Su-Jin Moon, Jennifer Lee, Seung-Ki Kwok, Sung-Hwan Park, Mi-La Cho
Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades cartilage and bone in rheumatoid arthritis (RA). FLS resistance to apoptosis is a major characteristic of RA. The aims of this study were to investigate the effects of interleukin-17 (IL-17) and IL-17-producing T helper (Th17) cells on resistance to apoptosis in FLSs from RA patients (RA FLSs) and their roles in mitochondrial dysfunction and autophagy. Mitochondrial function was assessed in RA FLSs and FLSs from osteoarthritis patients (OA FLSs)...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#6
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28100650/transforming-growth-factor-%C3%AE-suppresses-peroxisome-proliferator-activated-receptor-%C3%AE-expression-via-both-smad-binding-and-novel-tgf-%C3%AE-inhibitory-elements
#7
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ downregulation is prominent in fibrosis and mediated, via previously unknown mechanisms, by SMAD signaling. Here we show that TGF-β induces association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive corepressors E2F4 and p107...
January 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28098879/cytokines-inducers-and-inhibitors-modulate-mmp-2-and-mmp%C3%A2-9-secretion-by-human-fanconi-anemia-immortalized-fibroblasts
#8
M W Roomi, T Kalinovsky, M Rath, A Niedzwiecki
Acute myeloid leukemia and head and neck squamous cell carcinomas are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in tumor invasion and metastasis. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in the regulation of MMP-2 and MMP-9 in human immortalized fibroblasts from FA. Human FA immortalized fibroblast cell lines FA-A:PD220 and FA-D2:PD20 were grown in minimum essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and antibiotics in 24-well tissue culture plates...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28093936/biological-activities-of-rosmarinus-officinalis-l-rosemary-extract-as-analyzed-in-microorganisms-and-cells
#9
Jonatas Rafael de Oliveira, Daiane de Jesus, Leandro Wagner Figueira, Felipe Eduardo de Oliveira, Cristina Pacheco Soares, Samira Estves Afonso Camargo, Antonio Olavo Cardoso Jorge, Luciane Dias de Oliveira
R. officinalis L. is an aromatic plant commonly used as condiment and for medicinal purposes. Biological activities of its extract were evaluated in this study, as antimicrobial effect on mono- and polymicrobial biofilms, cytotoxicity, anti-inflammatory capacity, and genotoxicity. Monomicrobial biofilms of Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and Pseudomonas aeruginosa and polymicrobial biofilms composed of C. albicans with each bacterium were formed in microplates during 48 h and exposed for 5 min to R...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#10
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
https://www.readbyqxmd.com/read/28092351/pulmonary-complications-post-hematopoietic-stem-cell-transplant-in-dyskeratosis-congenita-analysis-of-oxidative-stress-in-lung-fibroblasts
#11
C Sorge, L Pereboeva, E Westin, W T Harris, D R Kelly, F Goldman
No abstract text is available yet for this article.
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28089357/localization-of-toll-like-receptor-tlr-2-and-tlr4-mrna-in-the-colorectal-mucosa-of-miniature-dachshunds-with-inflammatory-colorectal-polyps
#12
N Yokoyama, H Ohta, J Yamazaki, Y Kagawa, O Ichii, N Khoirun, T Morita, T Osuga, S Y Lim, N Sasaki, K Morishita, K Nakamura, M Takiguchi
Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay...
January 12, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28079159/socs1-favors-the-epithelial-mesenchymal-transition-in-melanoma-promotes-tumor-progression-and-prevents-antitumor-immunity-by-pd-l1-expression
#13
R Berzaghi, V S C Maia, F V Pereira, F M Melo, M S Guedes, C S T Origassa, J B Scutti, A L Matsuo, N O S Câmara, E G Rodrigues, L R Travassos
Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. SOCS1 silencing inhibited cell migration and invasion as well as in vitro growth by cell cycle arrest at S phase with increased cell size and nuclei. Down-regulation of SOCS1 decreased the expression of epidermal growth factor receptor, Ins-Rα, and fibroblast growth factor receptors. The present work aimed at analyzing the SOCS1 cell signaling and expression of proteins relevant to tumor development...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077599/blt1-mediates-bleomycin-induced-lung-fibrosis-independently-of-neutrophils-and-cd4-t-cells
#14
Jiaoyan Lv, Yingluo Xiong, Wenjing Li, Wei Yang, Lina Zhao, Rui He
Leukotriene B4 (LTB4) and its functional receptor BLT1 are closely involved in tissue inflammation by primarily mediating leukocyte recruitment and activation. Elevated LTB4 was reported in patients with lung fibrosis; however, the role of the LTB4/BLT1 axis in lung fibrosis remains unknown. In this study, we demonstrated that BLT1(-/-) mice exhibited significantly attenuated bleomycin (BLM)-induced lung fibrosis. Interestingly, BLT1 blockade with its specific antagonist U75302 in the acute injury phase (days 0-10 after BLM treatment) significantly attenuated lung fibrosis, which was accompanied by significant decreases in early infiltrating neutrophils and later infiltrating CD4(+) T cells and the production of TGF-β, IL-13, and IL-17A...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077438/fibroblast-drug-scavenging-increases-intratumoural-gemcitabine-accumulation-in-murine-pancreas-cancer
#15
E Hessmann, M S Patzak, L Klein, N Chen, V Kari, I Ramu, T E Bapiro, K K Frese, A Gopinathan, F M Richards, D I Jodrell, C Verbeke, X Li, R Heuchel, J M Löhr, S A Johnsen, T M Gress, V Ellenrieder, A Neesse
OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28075411/tamaractam-a-new-bioactive-lactam-from-tamarix-ramosissima-induces-apoptosis-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#16
Yao Yao, Cheng-Shuai Jiang, Na Sun, Wei-Qi Li, Yang Niu, Huai-Qin Han, Zhen-Hua Miao, Xun-Xia Zhao, Jing Zhao, Juan Li
Chemical investigation of Tamarix ramosissima Ledeb, a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China, led to the discovery of a new phenolic aromatic rings substituted lactam, tamaractam (1), together with the previously reported compounds cis-N-feruloyl-3-O-methyldopamine (2) and trans-N-feruloyl-3-O-methyldopamine (3). The structures of the compounds were determined by high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, as well as comparison with the literature data...
January 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28063251/perivascular-adipose-tissue-inflammation-in-vascular-disease
#17
REVIEW
Ryszard Nosalski, Tomasz J Guzik
Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso-protective adipocyte derived relaxing factors (ADRFs) and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6, TNF-α) and chemokines (RANTES, MCP-1)...
January 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28062850/cellular-strain-avoidance-is-mediated-by-a-functional-actin-cap-observations-in-an-lmna-deficient-cell-model
#18
Chiara Tamiello, Maurice Halder, Miriam A F Kamps, Frank P T Baaijens, Jos L V Broers, Carlijn V C Bouten
In adherent cells the relevance of a physical mechanotransduction pathway provided by the perinuclear actin cap stress fibers has recently emerged. Here, we investigate the impact of a functional actin cap on the cellular adaptive response to topographical cues and uniaxial cyclic strain. Lmna-deficient fibroblasts are used as a model system because they do not develop an intact actin cap, but predominantly form a basal layer of actin stress fibers underneath the nucleus. We observe that topographical cues induce alignment in both normal and lmna-deficient fibroblasts, suggesting that topographical signal transmission occurs independently of the integrity of the actin cap...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28062234/in-vitro-antiprotozoal-activity-of-s-cis-verbenol-against-leishmania-spp-and-trypanosoma-cruzi
#19
Gloria Yaluff, Celeste Vega, Nelson Alvarenga
(S)-cis-Verbenol, a monoterpene frequently found as a component of essential oils, was assayed against Leishmania amazonensis, Leishmania infantum, Leishmania brasiliensis and against two strains of Trypanosoma cruzi. The cytotoxicity of the compound was also assayed against human fibroblast cells using a colorimetric method. Benznidazole was used as reference drug against T. cruzi and amphotericin B was used against Leishmania spp. The compound showed good activity against the trypanosomes, being more active against the CL Brenner strain, with an IC50 value of 8...
January 3, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28060853/a-cationic-amphiphilic-random-copolymer-with-ph-responsive-activity-against-methicillin-resistant-staphylococcus-aureus
#20
Sungyoup Hong, Haruko Takahashi, Enrico T Nadres, Hamid Mortazavian, Gregory A Caputo, John G Younger, Kenichi Kuroda
In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S...
2017: PloS One
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