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https://www.readbyqxmd.com/read/28429728/a-formulated-tlr7-8-agonist-is-a-flexible-highly-potent-and-effective-adjuvant-for-pandemic-influenza-vaccines
#1
Neal Van Hoeven, Christopher B Fox, Brian Granger, Tara Evers, Sharvari W Joshi, Ghislain I Nana, Sarah C Evans, Susan Lin, Hong Liang, Li Liang, Rie Nakajima, Philip L Felgner, Richard A Bowen, Nicole Marlenee, Airn Hartwig, Susan L Baldwin, Rhea N Coler, Mark Tomai, James Elvecrog, Steven G Reed, Darrick Carter
Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28406067/rna-and-a-cell-wall-component-of-enterococcus-faecalis-ic-1-are-required-for-phagocytosis-and-interleukin-12-production-by-the-mouse-macrophage-cell-line-j774-1
#2
Junpei Nakase, Yuuichi Ukawa, Syoji Takemoto, Takayoshi Kubo, Yuko M Sagesaka, Ayako Aoki-Yoshida, Mamoru Totsuka
Enterococcus faecalis is a resident lactic acid bacterium in the human intestine. Its immunostimulatory action was reported to be enhanced by heat sterilization. To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12-inducing ability. Furthermore, we investigated the underlying mechanism by treating IC-1 cells with RNase or lysozyme...
April 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28342266/increased-number-of-mast-cells-in-the-dermis-in-actinic-keratosis-lesions-effectively-treated-with-imiquimod
#3
Satomi Oyama, Yoko Funasaka, Shin-Ichi Tsuchiya, Seiji Kawana, Hidehisa Saeki
Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions...
March 24, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28323387/induction-of-tumor-regression-by-intratumoral-sting-agonists-combined-with-anti-programmed-death-l1-blocking-antibody-in-a-preclinical-squamous-cell-carcinoma-model
#4
Shekhar K Gadkaree, Juan Fu, Rupashree Sen, Michael J Korrer, Clint Allen, Young J Kim
BACKGROUND: Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have demonstrated antitumor activity in melanoma and breast tumors, although their role in immunotherapy of head and neck squamous cell cancers (HNSCCs) has not been well investigated. METHODS: We measured primary tumor growth rates, mechanism of antitumor activity, and efficacy of programmed death-L1 blockade combinatorial therapy in SCCFVII tumor-bearing C3H/HeOUJ mice undergoing intratumoral injections with RR-cyclic-di-guanine (synthetic CDG), CDG (natural cyclic-di-guanine), R848 (TLR 7/8 agonist), or phosphate buffered saline (PBS, control)...
March 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28273784/thymosin-%C3%AE-1-expands-deficient-il-10-producing-regulatory-b-cell-subsets-in-relapsing-remitting-multiple-sclerosis-patients
#5
Elena Giacomini, Fabiana Rizzo, Marilena P Etna, Melania Cruciani, Rosella Mechelli, Maria Chiara Buscarinu, Francesca Pica, Cartesio D'Agostini, Marco Salvetti, Eliana M Coccia, Martina Severa
BACKGROUND: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population. OBJECTIVES: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing-remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28262752/highly-exposed-hiv-1-seronegative-female-commercial-sex-workers-sustain-in-their-genital-mucosa-increased-frequencies-of-tolerogenic-myeloid-and-regulatory-t-cells
#6
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246456/nutrigenomic-evaluation-of-garlic-allium-sativum-and-holy-basil-ocimum-sanctum-leaf-powder-supplementation-on-growth-performance-and-immune-characteristics-in-broilers
#7
N Sheoran, R Kumar, A Kumar, K Batra, S Sihag, S Maan, N S Maan
AIM: In this study, a planned research work was conducted to investigate the nutrigenomic aspects of supplementation of Allium sativum (garlic) and Ocimum sanctum (holy basil) leaf powder on the growth performance and immune characteristics of broilers. MATERIALS AND METHODS: A 6 weeks feeding trial was conducted with 280-day-old Ven Cobb broilers, distributed randomly into seven experimental groups. Each treatment had 4 replicates with 10 birds each. The birds of the control group (T1) were fed a basal diet formulated as per BIS standards...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28131813/microrna-146a-induction-during-influenza-h3n2-virus-infection-targets-and-regulates-traf6-levels-in-human-nasal-epithelial-cells-hnecs
#8
Yuqin Deng, Yan Yan, Kai Sen Tan, Jing Liu, Vincent T Chow, Ze-Zhang Tao, De-Yun Wang
We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for respiratory viruses including influenza A virus (IAV) and respiratory syncytial virus. Recent studies have indicated that microRNAs (miRNAs) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hNECs model derived from multiple donors. By comparing the differential expression of miRNAs upon IAV infection among animal and cell line studies, candidates were selected with focus on the initial immune response...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28114604/topical-imiquimod-plus-nab-paclitaxel-for-breast-cancer-cutaneous-metastases-a-phase-2-clinical-trial
#9
Lupe G Salazar, Hailing Lu, Jessica L Reichow, Jennifer S Childs, Andrew L Coveler, Doreen M Higgins, James Waisman, Kimberly H Allison, Yushe Dang, Mary L Disis
Importance: Salvage chemotherapy for recurrent chest wall lesions in breast cancer results in response rates of 20% to 30%. Preclinical studies showed significant disease regression could be induced in murine chest wall mammary cancers with a topical toll-like receptor (TLR)-7 agonist, imiquimod. Objective: To evaluate the safety and objective response rate (ORR) of imiquimod in combination with systemic albumin bound paclitaxel in treatment-refractory breast cancer of the chest wall...
January 19, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28098883/developmental-expression-of-toll%C3%A2-like-receptors-in-the-guinea-pig-lung
#10
Lingjie Ma, Jiali Yang, Li Yang, Juan Shi, Jing Xue, Yong Li, Xiaoming Liu
The guinea pig is a useful model for investigating infectious and non‑infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll‑like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using cell type‑specific markers...
March 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-fas-lpr-mice
#11
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28054376/toll-like-receptor-tlr-7-expression-in-mycosis-fungoides-and-psoriasis-a-case-control-study
#12
A M El Tawdy, I M Amin, R M Abdel Hay, A S Hassan, Z S Gad, L A Rashed
BACKGROUND: Toll-like receptors (TLRs) have been implicated in various dermatological diseases. TLR agonists have the capacity to potently activate the innate immune cells of patients with advanced, refractory, cutaneous T-cell lymphoma (CTCL). AIM: To detect TLR7 gene expression in mycosis fungoides (MF) (a neoplastic skin condition) and to compare it with psoriasis (an inflammatory skin condition) in an attempt to clarify the pathogenic role played by TLR7 in both conditions...
January 5, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28052637/future-anti-hbv-strategies
#13
REVIEW
Edward J Gane
Although current oral antivirals can maintain viral suppression and reduce the risk of liver-related complications, lifelong therapy is associated with high cost, risk of breakthrough and potential toxicity. There is a need to develop a finite course of treatment which can provide sustained off-treatment virological and clinical response. The likely marker of such a clinical HBV CURE would be HBsAg clearance, but in addition cccDNA elimination would be required to prevent future reactivation (ie complete HBV cure)...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28052019/tlr-activated-plasmacytoid-dendritic-cells-inhibit-breast-cancer-cell-growth-in-vitro-and-in-vivo
#14
Jing Wu, Shuang Li, Yang Yang, Shan Zhu, Mingyou Zhang, Yuan Qiao, Yong-Jun Liu, Jingtao Chen
Plasmacytoid dendritic cells (pDCs) are a unique subset of naturally occurring dendritic cells, which triggers the production of large amounts of type I interferons (IFNs) after viral infections through Toll-like receptor (TLR) 7 and TLR9. Recent studies have demonstrated that the activation of pDCs kills melanoma cells. However, the role of activated pDCs in breast cancer remains to be determined. In the present study, we generated mouse models of breast cancer and demonstrated that activated pDCs can directly kill breast tumor cells through TRAIL and Granzyme B...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28043660/comparison-of-outcomes-after-treatment-of-in-stent-restenosis-using-newer-generation-drug-eluting-stents-versus-drug-eluting-balloon-patient-level-pooled-analysis-of-korean-multicenter-in-stent-restenosis-registry
#15
Joo Myung Lee, Tae-Min Rhee, Joo-Yong Hahn, Doyeon Hwang, Jonghanne Park, Kyung Woo Park, Hack-Lyoung Kim, Sang-Hyun Kim, In-Ho Chae, Joon-Hyung Doh, Ki-Hyun Jeon, Young Jin Choi, Jin Sik Park, Seung-Hyuck Choi, Hyeon-Cheol Gwon, Bon-Kwon Koo, Fernando Alfonso, Hyo-Soo Kim
BACKGROUND: Studies comparing the drug-eluting balloon (DEB) with contemporary drug-eluting stent (DES) in the treatment of in-stent restenosis (ISR) have been scarce. We compared that the efficacy and safety of contemporary DES versus DEB in unselected, real world patients of ISR occurred in bare-metal stent or DES. METHODS: Patient-level pooled analysis from nationwide multicenter registries was performed with 628 consecutive patients who underwent ISR treatment using 2nd or 3rd generation DES or DEB...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28036266/combining-vasculature-disrupting-agent-and-toll-like-receptor-7-8-agonist-for-cancer-therapy
#16
Anushree Seth, Hyunseung Lee, Mi Young Cho, Cheongsoo Park, Sovannarith Korm, Joo-Yong Lee, Inpyo Choi, Yong Taik Lim, Kwan Soo Hong
This study evaluates the effect of combination of two different treatment regimens for solid tumor therapy: vasculature targeting agent and immune-stimulation. Poly lactide-co-glycolide (PLGA) nanoparticles were synthesized for intracellular delivery of Toll-like receptor (TLR) 7/8 agonist-gardiquimod. Spherical and mono-disperse gardiquimod encapsulated PLGA nanoparticles (Gardi-PLGA), approximately 194 nm in size were formulated. Gardi-PLGA induced immune-stimulation, and vasculature disrupting agent (VDA)-5,6-Dimethylxanthenone-4-acetic acid (DMXAA) was used in combination to assessing the influence on bone marrow derived dendritic cells (BMDCs) and B16-F10 melanoma cells...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in%C3%A2-active-and-resolved-psoriasis
#17
Elisa Martini, Maria Wikén, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), were confined to lesional psoriasis and phenotypically distinct from dermal DCs. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 21, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27999742/reprogramming-of-tlr7-signaling-enhances-antitumor-nk-and-cytotoxic-t-cell-responses
#18
Christian Hotz, Marina Treinies, Ines Mottas, Laurin C Rötzer, Anne Oberson, Lorenzo Spagnuolo, Maurizio Perdicchio, Thibaud Spinetti, Tina Herbst, Carole Bourquin
Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly(I:C) that mimics virally induced immune activation...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27919753/advax-a-delta-inulin-microparticle-potentiates-in-built-adjuvant-property-of-co-administered-vaccines
#19
Masayuki Hayashi, Taiki Aoshi, Yasunari Haseda, Kouji Kobiyama, Edward Wijaya, Noriyuki Nakatsu, Yoshinobu Igarashi, Daron M Standley, Hiroshi Yamada, Yoshikazu Honda-Okubo, Hiromitsu Hara, Takashi Saito, Toshiyuki Takai, Cevayir Coban, Nikolai Petrovsky, Ken J Ishii
Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/27891600/human-pdcs-display-sex-specific-differences-in-type-i-interferon-subtypes-and-interferon-%C3%AE-%C3%AE-receptor-expression
#20
Susanne M Ziegler, Claudia Beisel, Kathrin Sutter, Morgane Griesbeck, Heike Hildebrandt, Sven H Hagen, Ulf Dittmer, Marcus Altfeld
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN-α subtypes...
November 28, 2016: European Journal of Immunology
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