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https://www.readbyqxmd.com/read/29155882/pharmacological-inhibition-of-ror%C3%AE-t-suppresses-the-th17-pathway-and-alleviates-arthritis-in-vivo
#1
Ulf Guendisch, Jessica Weiss, Florence Ecoeur, Julia Christina Riker, Klemens Kaupmann, Joerg Kallen, Samuel Hintermann, David Orain, Janet Dawson, Andreas Billich, Christine Guntermann
Retinoic acid receptor-related-orphan-receptor-C (RORγt) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORγt in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim of inhibiting the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in vitro and in vivo pharmacology of a potent and selective small-molecular-weight RORγt inverse agonist...
2017: PloS One
https://www.readbyqxmd.com/read/29149822/olive-leaf-extracts-act-as-modulators-of-the-human-immune-response
#2
Thea Magrone, Anna Spagnoletta, Rosaria Salvatore, Manrico Magrone, Francesco Dentamaro, Matteo Antonio Russo, Graziana Difonzo, Carmine Summo, Francesco Caponio, Emilio Jirillo
BACKGROUND: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. METHODS: Peripheral blood mononuclear cells (PBMCs) from twenty-five healthy donors were cultured in the presence of 3 μg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol)...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29123137/high-fraction-brookite-films-from-amorphous-precursors
#3
James E S Haggerty, Laura T Schelhas, Daniil A Kitchaev, John S Mangum, Lauren M Garten, Wenhao Sun, Kevin H Stone, John D Perkins, Michael F Toney, Gerbrand Ceder, David S Ginley, Brian P Gorman, Janet Tate
Structure-specific synthesis processes are of key importance to the growth of polymorphic functional compounds such as TiO2, where material properties strongly depend on structure as well as chemistry. The robust growth of the brookite polymorph of TiO2, a promising photocatalyst, has been difficult in both powder and thin-film forms due to the disparity of reported synthesis techniques, their highly specific nature, and lack of mechanistic understanding. In this work, we report the growth of high-fraction (~95%) brookite thin films prepared by annealing amorphous titania precursor films deposited by pulsed laser deposition...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122456/sentinels-of-the-type-2-immune-response
#4
REVIEW
Jakob von Moltke, Marion Pepper
Type 2 immune responses have evolved to sense and respond to large, non-replicating infections or non-microbial noxious compounds in tissues. The development of these responses therefore depends upon highly coordinated and tightly regulated tissue-residing cellular sensors and responders. Multiple exposure to type 2 helper T cell (Th2)-inducing stimuli further enhances both the diversity and potency of the response. This review discusses advances in our understanding of the interacting cellular subsets that comprise both primary and secondary type 2 responses...
November 6, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/29075248/the-exometabolome-of-two-model-strains-of-the-roseobacter-group-a-marketplace-of-microbial-metabolites
#5
Gerrit Wienhausen, Beatriz E Noriega-Ortega, Jutta Niggemann, Thorsten Dittmar, Meinhard Simon
Recent studies applying Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) showed that the exometabolome of marine bacteria is composed of a surprisingly high molecular diversity. To shed more light on how this diversity is generated we examined the exometabolome of two model strains of the Roseobacter group, Phaeobacter inhibens and Dinoroseobacter shibae, grown on glutamate, glucose, acetate or succinate by FT-ICR-MS. We detected 2,767 and 3,354 molecular formulas in the exometabolome of each strain and 67 and 84 matched genome-predicted metabolites of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29066866/halofuginone-ameliorates-inflammation-in-severe-acute-hepatitis-b-virus-hbv-infected-sd-rats-through-ampk-activation
#6
Weili Zhan, Yanhong Kang, Ning Chen, Chongshan Mao, Yi Kang, Jia Shang
The hepatitis B virus (HBV) has caused acute and chronic liver diseases in ~350 million infected people worldwide. Halofuginone (HF) is a plant alkaloid which has been demonstrated to play a crucial role in immune regulation. Our present study explored the function of HF in the immune response of HBV-infected Sprague Dawley (SD) rats. Plasmid containing pCDNA3.1-HBV1.3 was injected in SD rats for the construction of an acute HBV-infected animal model. Our data showed that HF reduced the high concentrations of serum hepatitis B e-antigen, hepatitis B surface antigen, and HBV DNA induced by HBV infection...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28927768/synthesis-and-biological-evaluation-of-peptide-derived-tslp-inhibitors
#7
Seonghu Park, Yeeun Park, Sang-Hyun Son, Kiho Lee, Yong Woo Jung, Ki Yong Lee, Young Ho Jeon, Youngjoo Byun
Thymic stromal lymphopoietin (TSLP) is a type II cytokine which is associated with most inflammatory allergic disorders in humans. It is produced mainly by epithelial cells with important role in the development of chronic inflammatory diseases by activating T-helper cell type-2 (TH2) pathways. In this study, a total of 16 peptides were prepared by solid phase peptide synthesis based on amino acid sequences of the interface between TSLP and TSLP receptor. Their TSLP inhibition activities were determined by ELISA assay...
October 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28790504/cigarette-smoke-and-dna-cleavage-promote-lung-inflammation-and-emphysema
#8
Farrah Kheradmand, R You, Bon Hee Gu, D B Corry
Smoking-related lung diseases are among the most preventable and incurable ailments in the world. Smokers are at increased risk of developing chronic obstructive pulmonary disease that can be further complicated by emphysema and lung cancer. A subset of former smokers shows persistent lung inflammation and progressive loss of lung function, indicating a role for activation of acquired immunity in smoking-induced lung diseases. In addition to the well-established noxious effects of volatile compounds in cigarette smoke, incomplete combustion of tobacco generates nano-sized carbon black (nCB) that accumulate in lung myeloid dendritic cells and macrophages...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28698674/insight-into-synergetic-mechanisms-of-tetracycline-and-the-selective-serotonin-reuptake-inhibitor-sertraline-in-a-tetracycline-resistant-strain-of-escherichia-coli
#9
Lili Li, Sofie Kromann, John Elmerdahl Olsen, Søren Wedel Svenningsen, Rikke Heidemann Olsen
Sertraline, an antidepressive drug, has been reported to inhibit general bacterial efflux pumps. In the present study, we report for the first time a synergistic effect of sertraline and tetracycline in a TetA-encoded tetracycline-resistant strain of Escherichia coli. Synergy between sertraline and tetracycline in an E. coli strain with TetA-mediated tetracycline resistance (E. coli APEC_O2) was assessed by the MIC and checkerboard assays. The global transcriptome of E. coli APEC_O2 exposed to ½ MIC concentrations of sertraline and/or tetracycline was analyzed to elucidate the interaction mechanism between sertraline and tetracycline...
August 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28681958/bj-2266-ameliorates-experimental-autoimmune-encephalomyelitis-through-down-regulation-of-the-jak-stat-signaling-pathway
#10
Zhiwei You, Maheshwor Timilshina, Byeong-Seon Jeong, Jae-Hoon Chang
CD4(+) T cells differentiate into distinct effector subsets upon antigenic stimulation. Cytokines, and micro-environmental factors present during T-cell priming, direct differentiation of naïve CD4(+) T cells into pro-inflammatory Th1 and Th17 cells. From extensive screening of 2,4,5-trimethylpyridin-3-ol derivatives with various functional groups at C(6)-position, BJ-2266, a 6-thioureido-derivative, showed potent inhibitory activity on in vitro T helper (Th)-cell differentiation. This compound inhibited IFN-γ and IL-17 production from polyclonal CD4(+) T cells and ovalbumin (OVA)-specific CD4(+) T cells that were activated by T-cell receptor (TCR) engagement...
September 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28674946/toxin-transport-by-a-b-type-of-toxins-in-eukaryotic-target-cells-and-its-inhibition-by-positively-charged-heterocyclic-molecules
#11
Roland Benz, Holger Barth
A-B types of toxins are among the most potent bacterial protein toxins produced by gram-positive bacteria. Prominent examples are the tripartite anthrax toxin of Bacillus anthracis and the different A-B type clostridial toxins that are the causative agents of severe human and animal diseases and could serve as biological weapons. The components of all these toxins comprise one binding/transport (B) subunit and one or two separate, non-linked enzymatically active (A) subunits. The A and B subunits are separately produced and secreted by the pathogenic gram-positive bacteria and must assemble on the surface of eukaryotic target cells to form biologically active toxin complexes...
July 4, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28658553/type-two-innate-lymphoid-cells-the-janus-cells-in-health-and-disease
#12
REVIEW
Hadi Maazi, Omid Akbari
Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28575798/design-and-computational-support-for-the-binding-stability-of-a-new-ccr5-cxcr4-dual-tropic-inhibitor-computational-design-of-a-ccr5-cxcr4-drug
#13
Cooper A Taylor, Bill R Miller, Carol A Parish
The human immunodeficiency virus (HIV) infects healthy human cells by binding to the glycoprotein cluster of differentiation 4 receptors on the surface of helper T-cells, along with either of two chemokine receptors, CC chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4). Recently, a pyrazolo-piperdine ligand was synthesized and the corresponding biological data showed good binding to both chemokine receptors, effectively blocking HIV-1 entry. Here, we exhaustively assess the atomistic binding interactions of this compound with both CCR5 and CXCR4, and we find that binding is driven by π-stacking interactions between aromatic rings on the ligand and receptor residues, as well as electrostatic interactions involving the protonated piperidine nitrogen...
February 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28568565/inhibition-of-th1-and-th17-cells-by-medicinal-plants-and-their-derivatives-a-systematic-review
#14
REVIEW
Majid Asadi-Samani, Nader Bagheri, Mahmoud Rafieian-Kopaei, Hedayatollah Shirzad
Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases...
August 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28442542/missense-mutations-in-the-wd40-domain-of-ahi1-cause-non-syndromic-retinitis-pigmentosa
#15
Thanh-Minh T Nguyen, Sarah Hull, Ronald Roepman, L Ingeborgh van den Born, Machteld M Oud, Erik de Vrieze, Lisette Hetterschijt, Stef J F Letteboer, Sylvia E C van Beersum, Ellen A Blokland, Helger G Yntema, Frans P M Cremers, Paul A van der Zwaag, Gavin Arno, Erwin van Wijk, Andrew R Webster, Lonneke Haer-Wigman
BACKGROUND: Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). METHODS: Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling...
September 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28278183/systemic-thioridazine-in-combination-with-dicloxacillin-against-early-aortic-graft-infections-caused-by-staphylococcus-aureus-in-a-porcine-model-in-vivo-results-do-not-reproduce-the-in-vitro-synergistic-activity
#16
Michael Stenger, Carsten Behr-Rasmussen, Kasper Klein, Rasmus B Grønnemose, Thomas Emil Andersen, Janne K Klitgaard, Hans Jørn Kolmos, Jes S Lindholt
INTRODUCTION: Conservative treatment solutions against aortic prosthetic vascular graft infection (APVGI) for inoperable patients are limited. The combination of antibiotics with antibacterial helper compounds, such as the neuroleptic drug thioridazine (TDZ), should be explored. AIM: To investigate the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model...
2017: PloS One
https://www.readbyqxmd.com/read/28276465/cytochrome-p450s-in-human-immune-cells-regulate-il-22-and-c-kit-via-an-ahr-feedback-loop
#17
Renate Effner, Julia Hiller, Stefanie Eyerich, Claudia Traidl-Hoffmann, Knut Brockow, Massimo Triggiani, Heidrun Behrendt, Carsten B Schmidt-Weber, Jeroen T M Buters
The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197348/angioimmunoblastic-t-cell-lymphoma-a-questionable-association-with-follicular-dendritic-cell-sarcoma
#18
Daniel Benharroch, Miriam Zekzer, Karen Nalbandyan
An elderly woman presented with generalized lymphadenopathy, several systemic symptoms, and splenomegaly. An inguinal lymph node excision revealed a compound picture. One aspect of the lymph node morphology, including cells with follicular T-helper cell phenotype, was most consistent with angioimmunoblastic T-cell lymphoma. The other component, revealing spindle cells forming whorls with immunostaining for CD21, CD23, and fascin, might be an integral part of this T-cell lymphoma. However, due to the often massive involvement of the nodal tissue by these follicular dendritic cells, these areas were questionably suggestive of involvement by follicular dendritic cell sarcoma...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28169371/novel-benzoxazole-derivatives-dcpab-and-hpab-attenuate-th1-cell-mediated-inflammation-through-t-bet-suppression
#19
Yeon Ji Oh, Darong Kim, Sera Oh, Eun Jung Jang, Hee Yeon Won, Hana Jeong, Mi Gyeong Jeong, Hea-Young Park Choo, Eun Sook Hwang
Interferon-γ (IFN-γ), a critical inflammatory cytokine, is primarily produced by T helper 1 (Th1) cells and accelerates the pathogenesis of inflammatory colitis. Pharmacological suppression of IFN-γ production attenuates dysregulated inflammatory responses and may be beneficial for treating inflammatory disease. In this study, we aimed to discover potent anti-inflammatory compounds that suppress IFN-γ production and found that the novel benzoxazole derivatives, 2-((3,4-dichlorophenyl) amino) benzo[d]xazol-5-ol (DCPAB) and 2-((3,4-hydroxyphenyl) amino) benzo[d]xazol-5-ol (HPAB), suppressed IFN-γ production by T cells...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28146629/identification-of-high-potency-human-tlr8-and-dual-tlr7-tlr8-agonists-in-pyrimidine-2-4-diamines
#20
Mallesh Beesu, Alex C D Salyer, Michael J H Brush, Kathryn L Trautman, Justin K Hill, Sunil A David
The induction of toll-like receptor 7 (TLR7)-dependent type I interferons (IFN-α/β) from plasmacytoid dendritic cells as well as the production of TLR8-dependent type II interferon (IFN-γ), TNF-α, and IL-12 in myeloid dendritic cells are of importance in generating T helper-1 biased adaptive immune responses. In an effort to identify novel dual TLR7/TLR8-active compounds, we undertook structure-activity relationship studies in pyrimidine 2,4-diamines, focusing on substituents at C5. Several analogues substituted with aminopropyl appendages at C5 displayed dominant TLR8-agonistic activity...
March 9, 2017: Journal of Medicinal Chemistry
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