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https://www.readbyqxmd.com/read/28927768/synthesis-and-biological-evaluation-of-peptide-derived-tslp-inhibitors
#1
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...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28790504/cigarette-smoke-and-dna-cleavage-promote-lung-inflammation-and-emphysema
#2
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
#3
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
#4
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...
July 6, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28146477/feedback-control-of-ahr-signalling-regulates-intestinal-immunity
#15
Chris Schiering, Emma Wincent, Amina Metidji, Andrea Iseppon, Ying Li, Alexandre J Potocnik, Sara Omenetti, Colin J Henderson, C Roland Wolf, Daniel W Nebert, Brigitta Stockinger
The aryl hydrocarbon receptor (AHR) recognizes xenobiotics as well as natural compounds such as tryptophan metabolites, dietary components and microbiota-derived factors, and it is important for maintenance of homeostasis at mucosal surfaces. AHR activation induces cytochrome P4501 (CYP1) enzymes, which oxygenate AHR ligands, leading to their metabolic clearance and detoxification. Thus, CYP1 enzymes have an important feedback role that curtails the duration of AHR signalling, but it remains unclear whether they also regulate AHR ligand availability in vivo...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/28138745/direct-aqueous-measurement-of-25-hydroxyvitamin-d-levels-in-a-cellular-environment-by-lc-ms-ms-using-the-novel-chemical-derivatization-reagent-mdbp
#16
Miriam J Müller, Heiko Bruns, Dietrich A Volmer
Vitamin D measurements in biological fluids by mass spectrometry are challenging at very low concentration levels. As a result, chemical derivatization is often employed to enhance the ionization properties of low abundant vitamin D compounds. Cookson-type reagents such as 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) or similar derivatives work well but require careful, water-free experimental conditions, as traces of water inactivate the reagent and inhibit or stop the derivatization reactions, thus making quantitative measurements in aqueous samples impossible...
January 30, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28130500/synthetic-retinoid-am80-ameliorates-lung-and-arthritic-autoimmune-responses-by-inhibiting-t-follicular-helper-and-th17-cell-responses
#17
Debdut Naskar, Fei Teng, Krysta M Felix, C Pierce Bradley, Hsin-Jung Joyce Wu
Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28121465/topical-application-of-the-anti-microbial-chemical-triclosan-induces-immunomodulatory-responses-through-the-s100a8-a9-tlr4-pathway
#18
Nikki B Marshall, Ewa Lukomska, Ajay P Nayak, Carrie M Long, Justin M Hettick, Stacey E Anderson
The anti-microbial compound triclosan is incorporated into numerous consumer products and is detectable in the urine of 75% of the general United States population. Recent epidemiological studies report positive associations with urinary triclosan levels and allergic disease. Although not sensitizing, earlier studies previously found that repeated topical application of triclosan augments the allergic response to ovalbumin (OVA) though a thymic stromal lymphopoietin (TSLP) pathway in mice. In the present study, early immunological effects following triclosan exposure were further evaluated following topical application in a murine model...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28119186/phytosterols-isolated-from-clinacanthus-nutans-induce-immunosuppressive-activity-in-murine-cells
#19
Cheng-Foh Le, Thina Hareesh Kailaivasan, Sek-Chuen Chow, Zunoliza Abdullah, Sui-Kiong Ling, Chee-Mun Fang
Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C...
March 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28111810/mutual-effect-of-cerebral-amyloid-%C3%AE-and-peripheral-lymphocytes-in-cognitively-normal-older-individuals
#20
Fumihiko Yasuno, Hiroaki Kazui, Katsufumi Kajimoto, Masafumi Ihara, Naomi Morita, Akihiko Taguchi, Akihide Yamamoto, Kiwamu Matsuoka, Masato Takahashi, Jyoji Nakagawara, Masahito Tsuji, Hidehiro Iida, Toshifumi Kishimoto, Kazuyuki Nagatsuka
OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [(11) C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aβ deposition was quantified by cortical binding potential (PiB-BPND )...
January 23, 2017: International Journal of Geriatric Psychiatry
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