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https://www.readbyqxmd.com/read/29140706/a-galactosylated-pro-drug-of-ursodeoxycholic-acid-design-synthesis-characterization-and-pharmacological-effects-in-a-rat-model-of-estrogen-induced-cholestasis
#1
Francesca Di Guida, Claudio Pirozzi, Salvatore Magliocca, Anna Santoro, Adriano Lama, Roberto Russo, Maria Nieddu, Lucia Burrai, Gianpiero Boatto, Maria Pina Mollica, Federica Sodano, Loretta Lazzarato, Konstantin Chegaev, Rosaria Meli, Giuseppina Mattace Raso, Maria Grazia Rimoli
Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#3
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136128/the-proton-activated-receptor-gpr4-modulates-intestinal-inflammation
#4
Yu Wang, Cheryl de Vallière, Pedro H Imenez Silva, Irina Leonardi, Sven Gruber, Alexandra Gerstgrasser, Hassan Melham, Achim Weber, Katharina Leucht, Lutz Wolfram, Martin Hausmann, Carsten Krieg, Koray Thomasson, Onur Boyman, Isabelle Frey-Wagner, Gerhard Rogler, Carsten A Wagner
BACKGROUND AND AIMS: During active inflammation tissue intraluminal intestinal pH is decreased in patients with inflammatory bowel disease (IBD). Acidic pH may play a role in IBD pathophysiology. Recently, proton sensing G-protein coupled receptors were identified, including GPR4, OGR1 (GPR68), and TDAG8 (GPR65). We investigated whether GPR4 is involved in intestinal inflammation. METHODS: The role of GPR4 was assessed in murine colitis models: chronic dextran sulphate sodium (DSS) administration and by crossbreeding into an IL-10 deficient background for development of spontaneous colitis...
November 9, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29133955/chemokines-in-depression-in-health-and-in-inflammatory-illness-a-systematic-review-and-meta-analysis
#5
REVIEW
S P Leighton, L Nerurkar, R Krishnadas, C Johnman, G J Graham, J Cavanagh
Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participants with physical illness for subgroup analysis, and excluded participants with comorbid psychiatric diagnoses...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29133633/altered-tear-inflammatory-profile-in-indian-keratoconus-patients-the-2015-col-rangachari-award-paper
#6
Rohit Shetty, Rashmi Deshmukh, Arkasubhra Ghosh, Swaminathan Sethu, Chaitra Jayadev
PURPOSE: Conventionally, keratoconus (KC) has been considered a noninflammatory corneal ectatic disorder. Recent evidence suggests a possible role of inflammation in the pathogenesis of KC. Hence, we analyzed the levels of inflammatory factors in the tear fluid of Indian KC patients. METHODS: Tear fluid samples were collected from age- and sex-matched healthy controls and KC patients (with different grades). The levels of the inflammatory factors in tears were analyzed using cytometric bead array (Human Soluble Protein Flex Set System, BD Biosciences) for levels of interleukin-1α (IL-1α), IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12p70, IL-23p40, IL-13, IL-17A, IL-17F, IL-21, interferon-α (IFNα), IFNγ, tumor necrosis factor-α, CCL2/monocyte chemotactic protein-1, CCL4/macrophage inflammatory protein-1β (MIP-1β), MIP-1α, CCL5/RANTES, CXCL10/IP10, ICAM1, CD62E, vascular endothelial growth factor and transforming growth factor β...
November 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#7
Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29130936/jak2-binding-long-noncoding-rna-promotes-breast-cancer-brain-metastasis
#8
Shouyu Wang, Ke Liang, Qingsong Hu, Ping Li, Jian Song, Yuedong Yang, Jun Yao, Lingegowda Selanere Mangala, Chunlai Li, Wenhao Yang, Peter K Park, David H Hawke, Jianwei Zhou, Yan Zhou, Weiya Xia, Mien-Chie Hung, Jeffrey R Marks, Gary E Gallick, Gabriel Lopez-Berestein, Elsa R Flores, Anil K Sood, Suyun Huang, Dihua Yu, Liuqing Yang, Chunru Lin
Conventional therapies for breast cancer brain metastases (BCBMs) have been largely ineffective because of chemoresistance and impermeability of the blood-brain barrier. A comprehensive understanding of the underlying mechanism that allows breast cancer cells to infiltrate the brain is necessary to circumvent treatment resistance of BCBMs. Here, we determined that expression of a long noncoding RNA (lncRNA) that we have named lncRNA associated with BCBM (Lnc-BM) is prognostic of the progression of brain metastasis in breast cancer patients...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29129226/measuring-bovine-%C3%AE-%C3%AE-t-cell-function-at-the-site-of-mycobacterium-bovis-infection
#9
Rachel A Rusk, Mitchell V Palmer, W Ray Waters, Jodi L McGill
Bovine γδ T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/γδ T cell co-culture system to elucidate the role of γδ T cells in local immunity to M. bovis infection. Transcriptomics analysis revealed that γδ T cells upregulated expression of several novel, immune-associated genes in response to stimulation with M. bovis antigen...
December 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29123421/lncrna-expression-in-the-spinal-cord-modulated-by-minocycline-in-a-mouse-model-of-spared-nerve-injury
#10
Zihao Liu, Ying Liang, Honghua Wang, Zhenhe Lu, Jinsheng Chen, Qiaodong Huang, Lei Sheng, Yinghong Ma, Huiying Du, Qingjuan Gong
Neuropathic pain is a common and refractory chronic pain that affects millions of people worldwide. Its underlying mechanisms are still unclear, but they may involve long noncoding RNAs (lncRNAs), which play crucial roles in a variety of biological functions, including nociception. We used microarrays to investigate the possible interactions between lncRNAs and neuropathic pain and identified 22,213 lncRNAs and 19,528 mRNAs in the spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29122683/high-cxcl10-ip-10-levels-are-a-hallmark-in-the-clinical-evolution-of-the-hiv-infection
#11
Jacqueline María Valverde-Villegas, Rúbia Marília de Medeiros, Joel Henrique Ellwanger, Breno Riegel Santos, Marineide Gonçalves de Melo, Sabrina Esteves de Matos Almeida, José Artur Bogo Chies
The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4(+)T-cells/mm(3) were compared with those who initiated treatment with <350CD4(+)T-cells/mm(3)...
November 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29121255/adipocyte-expression-of-slc19a1-links-dna-hypermethylation-to-adipose-tissue-inflammation-and-insulin-resistance
#12
Paul Petrus, Lucia Bialesova, Antonio Checa, Alastair Kerr, Shama Naz, Jesper Bäckdahl, Ana Gracia, Sofia Toft, Karin Dahlman-Wright, Per Hedén, Ingrid Dahlman, Craig E Wheelock, Peter Arner, Niklas Mejhert, Hui Gao, Mikael Rydén
Context: Insulin resistance (IR) is promoted by a chronic low-grade inflammation in white adipose tissue (WAT). The latter may be regulated through epigenetic mechanisms such as DNA-methylation. The one carbon cycle (1CC) is a central metabolic process governing DNA-methylation. Objective: To identify adipocyte-expressed 1CC genes linked to WAT inflammation, IR and their causal role. Design: Cohort study. Setting: Outpatient academic clinic...
November 7, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29116124/monocytes-from-patients-with-primary-ciliary-dyskinesia-show-enhanced-inflammatory-properties-and-produce-higher-levels-of-pro-inflammatory-cytokines
#13
M Cockx, M Gouwy, P Ruytinx, I Lodewijckx, A Van Hout, S Knoops, N Pörtner, I Ronsse, L Vanbrabant, V Godding, K De Boeck, J Van Damme, M Boon, S Struyf
Patients with Primary Ciliary Dyskinesia (PCD) suffer from recurrent upper and lower airway infections due to defects in the cilia present on the respiratory epithelium. Since chronic inflammatory conditions can cause changes in innate immune responses, we investigated whether monocytes isolated from the peripheral blood of pediatric PCD patients respond differently to inflammatory stimuli, compared to monocytes from healthy children and adults. The receptor for C5a (C5aR) was upregulated in PCD, whereas expression levels of the leukocyte chemoattractant receptors CCR1, CCR2, CCR5, BLT1 and FPR1 on PCD monocytes were similar to those on monocytes from healthy individuals...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115520/ccl2-ccr2-axis-induces-hepatocellular-carcinoma-invasion-and-epithelial-mesenchymal-transition-in%C3%A2-vitro-through-activation-of-the-hedgehog-pathway
#14
Huijie Zhuang, Gang Cao, Changhua Kou, Tao Liu
Chemokine (C-C motif) ligand 2 (CCL2) has been shown to play an important role in the regulation of tumor cell growth, metastasis and host immune response. CCL2 preferentially binds to the C-C chemokine receptor type 2 (CCR2), which is expressed in various tissues. However, the role of the CCL2/CCR2 axis in hepatocellular carcinoma (HCC) invasion and its molecular mechanisms remain unclear. The aim of this study was to elucidate this issue. The human HCC cell line MHCC-97H was treated with CCL2. Cyclopamine, a smoothened (SMO) antagonist, was used to inhibit SMO activity...
November 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29113965/mitochondrial-oxidative-stress-reduces-the-immunopotency-of-mesenchymal-stromal-cells-in-adults-with-coronary-artery-disease
#15
Ozge Kizilay Mancini, Maximilien Lora, Alexanne Cuillerier, Dominique Shum-Tim, Reggie C Hamdy, Yan Burelle, Marc J Servant, Ursula Stochaj, Ines Colmegna
Rationale: Mesenchymal stromal cells (MSCs) are promising therapeutic strategies for coronary artery disease (CAD), however, donor-related variability in cell quality is a main cause of discrepancies in preclinical studies. In vitro, MSCs from individuals with CAD have reduced ability to suppress activated T-cells. The mechanisms underlying the altered immunomodulatory capacity of MSCs in the context of atherosclerosis (ATH) remain elusive. Objective: The aim of this study was to assess the role of mitochondrial dysfunction in the impaired immunomodulatory properties of MSCs from ATH patients...
November 7, 2017: Circulation Research
https://www.readbyqxmd.com/read/29113923/effects-of-spinal-non-viral-interleukin-10-gene-therapy-formulated-with-d-mannose-in-neuropathic-interleukin-10-deficient-mice-behavioral-characterization-mrna-and-protein-analysis-in-pain-relevant-tissues
#16
Arden G Vanderwall, Shahani Noor, Melody S Sun, Jacob E Sanchez, Xuexian O Yang, Lauren L Jantzie, Nikolaos Mellios, Erin D Milligan
Studies show that spinal (intrathecal; i.t.) interleukin-10 (IL-10) gene therapy reverses neuropathic pain in animal models, and co-administration with the mannose receptor (MR; CD206) ligand d-mannose (DM) greatly improves therapeutic efficacy. However, the actions of endogenous IL-10 may be required for enduring pain control observed following i.t. IL-10 gene therapy, potentially narrowing the application of this non-viral transgene delivery approach. Here, we show that i.t. application of naked plasmid DNA expressing the IL-10 transgene co-injected with DM (DM/pDNA-IL-10) for the treatment of peripheral neuropathic pain in IL-10 deficient (IL-10 KO) mice results in a profound and prolonged bilateral pain suppression...
November 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29113298/il-8-gro-and-mcp-1-produced-by-hepatocellular-carcinoma-microenvironment-determine-the-migratory-capacity-of-human-bone-marrow-derived-mesenchymal-stromal-cells-without-affecting-tumor-aggressiveness
#17
Juan Bayo, Alejandrina Real, Esteban J Fiore, Mariana Malvicini, Leonardo Sganga, Marcela Bolontrade, Oscar Andriani, Carolina Bizama, Cristóbal Fresno, Osvaldo Podhajcer, Elmer Fernandez, Manuel Gidekel, Guillermo D Mazzolini, Mariana G García
New therapies are needed for advanced hepatocellular carcinoma (HCC) and the use of mesenchymal stromal cells (MSCs) carrying therapeutic genes is a promising strategy. HCC produce cytokines recruiting MSCs to the tumor milieu and modifying its biological properties. Our aim was to study changes generated on human MSCs exposed to conditioned media (CM) derived from human HCC fresh samples and xenografts. All CM shared similar cytokines expression pattern including CXCL1-2-3/GRO, CCL2/MCP-1 and CXCL8/IL-8 being the latter with the highest concentration...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111308/inhibition-of-microrna-210-suppresses-pro-inflammatory-response-and-reduces-acute-brain-injury-of-ischemic-stroke-in-mice
#18
Lei Huang, Qingyi Ma, Yong Li, Bo Li, Lubo Zhang
Stroke is a leading cause of mortality and chronic neurologic disability. Yet, the successful treatment remains limited. In this study, we investigated the efficacy and the mechanism of a novel treatment, microRNA-210 (miR-210) inhibition, in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-210-LNA (miR-210 inhibitor) or the negative control was administered via intracerebroventricular injection 24h prior or 4h after MCAO...
October 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29111236/reprint-of-dual-blockade-of-the-pro-inflammatory-chemokine-ccl2-and-the-homeostatic-chemokine-cxcl12-is-as-effective-as-high-dose-cyclophosphamide-in-murine-proliferative-lupus-nephritis
#19
Satish Kumar Devarapu, Santhosh Kumar Vr, Khader Valli Rupanagudi, Onkar P Kulkarni, Dirk Eulberg, Sven Klussmann, Hans-Joachim Anders
Induction therapy of proliferative lupus nephritis still requires the use of unselective immunosuppressive drugs with significant toxicities. In search of more specific drugs with equal efficacy but fewer side effects we considered blocking pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) and homeostatic chemokine stromal cell-derived factor-1 (SDF-1/CXCL12), which both contribute to the onset and progression of proliferative lupus nephritis yet through different mechanisms. We hypothesized that dual antagonism could be as potent on lupus nephritis as the unselective immunosuppressant cyclophosphamide (CYC)...
October 27, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29109793/acute-inflammatory-response-following-increased-blood-brain-barrier-permeability-induced-by-focused-ultrasound-is-dependent-on-microbubble-dose
#20
Dallan McMahon, Kullervo Hynynen
Rationale: Focused ultrasound (FUS), in conjunction with circulating microbubbles (MBs), can be used to transiently increase the permeability of the blood-brain barrier (BBB) in a targeted manner, allowing therapeutic agents to enter the brain from systemic circulation. While promising preclinical work has paved the way for the initiation of 3 human trials, there remains concern regarding neuroinflammation following treatment. The aim of this study was to assess the magnitude of this response following sonication and explore the influence of MB dose...
2017: Theranostics
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