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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
#1
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
#2
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
#3
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
#4
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
#5
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...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28146477/feedback-control-of-ahr-signalling-regulates-intestinal-immunity
#6
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
#7
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
#8
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
#9
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
#10
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...
January 21, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28111810/mutual-effect-of-cerebral-amyloid-%C3%AE-and-peripheral-lymphocytes-in-cognitively-normal-older-individuals
#11
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
https://www.readbyqxmd.com/read/28095433/bj-3105-a-6-alkoxypyridin-3-ol-analog-impairs-t-cell-differentiation-and-prevents-experimental-autoimmune-encephalomyelitis-disease-progression
#12
Maheshwor Timilshina, Youra Kang, Ishmit Dahal, Zhiwei You, Tae-Gyu Nam, Keuk-Jun Kim, Byeong-Seon Jeong, Jae-Hoon Chang
CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement...
2017: PloS One
https://www.readbyqxmd.com/read/28032440/magnolol-attenuates-concanavalin-a-induced-hepatic-fibrosis-inhibits-cd4-t-helper-17-th17-cell-differentiation-and-suppresses-hepatic-stellate-cell-activation-blockade-of-smad3-smad4-signalling
#13
Hongjun Zhang, Baoling Ju, Xiaoli Zhang, Yanfei Zhu, Ying Nie, Yuanhong Xu, Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo...
December 29, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#14
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
March 2017: Immunology
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#15
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27852111/ror%C3%AE-t-inhibitors-as-potential-back-ups-for-the-phase-ii-candidate-vtp-43742-from-vitae-pharmaceuticals-patent-evaluation-of-wo2016061160-and-us20160122345
#16
Christian Gege
Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4(+) T cells and the production of T helper-17 (TH17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. Recently Vitae Pharmaceuticals (to be acquired by Allergan) reported positive top-line results from a Phase 2a clinical trial of RORγt inhibitor VTP-43742 in psoriatic patients...
January 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27756053/costunolide-a-sesquiterpene-lactone-inhibits-the-differentiation-of-pro-inflammatory-cd4-t-cells-through-the-modulation-of-mitogen-activated-protein-kinases
#17
Eunchong Park, Ju Han Song, Myun Soo Kim, Su-Ho Park, Tae Sung Kim
CD4(+) T cell activation and adequate differentiation into effector T helper (Th) cells are crucial for mediating adaptive immune responses to cope with foreign pathogens. Despite the significant role of Th cells, excessive increases in their numbers result in inflammatory and autoimmune diseases. In this study, we investigated the effects of costunolide, a plant-derived natural compound with an anti-inflammatory activity, in regulating Th cells and the underlying mechanisms. Costunolide significantly decreased cell populations of differentiated Th1, Th2, and Th17 subsets under Th subset-polarizing conditions, while exerting statistically negligible effects on Treg cell differentiation...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27751819/a-fumigaclavine-c-isostere-alleviates-th1-mediated-experimental-colitis-via-competing-with-ifn-%C3%AE-for-binding-to-ifn-%C3%AE-receptor-1
#18
Yang Tan, Xingxin Wu, Jing Sun, Wenjie Guo, Fangyuan Gong, Fenli Shao, Tao Tan, Yi Cao, Bingfeng Zheng, Yanhong Gu, Yang Sun, Qiang Xu
Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1)...
January 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27746240/protein-kinase-c%C3%AE-controls-type-2-innate-lymphoid-cell-and-th2-responses-to-house-dust-mite-allergen
#19
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response...
October 14, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27697049/macrolide-hybrid-compounds-drug-discovery-opportunities-in-anti-infective-and-anti-inflammatory-area
#20
Hana Čipčić Paljetak, Linda Tomašković, Mario Matijašić, Mirjana Bukvić, Andrea Fajdetić, Donatella Verbanac, Mihaela Perić
Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model...
September 27, 2016: Current Topics in Medicinal Chemistry
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