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https://www.readbyqxmd.com/read/28626766/involvement-of-the-toll-like-receptor-nitric-oxide-signaling-pathway-in-the-pathogenesis-of-cervical-cancer-caused-by-high-risk-human-papillomavirus-infection
#1
Jie Li, Heping Rao, Chang'e Jin, Jinrong Liu
Human papillomavirus (HPV) can activate Toll-like receptor (TLR)/nitric oxide (NO) signaling pathways; however, whether the TLR/NO pathway is involved in cervical cancer caused by high-risk HPV (HR-HPV) remains unclear. In this study, 43 HR-HPV-positive patients with cervical cancer (CC group), 39 HR-HPV-positive patients with a healthy cervix (HR-HPV group), and 33 HR-HPV-negative controls were recruited. NO concentration in cervical canal and expression of inducible NO synthase (iNOS) in cervical tissues were detected...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28592890/polymorphism-in-the-gene-encoding-toll-like-receptor-10-may-be-associated-with-asthma-after-bronchiolitis
#2
Sari Törmänen, Matti Korppi, Johanna Teräsjärvi, Juho Vuononvirta, Petri Koponen, Merja Helminen, Qiushui He, Kirsi Nuolivirta
Toll-like receptors (TLRs) recognise microbes that contribute to the severity of bronchiolitis and the subsequent risk of asthma. We evaluated whether post-bronchiolitis asthma was associated with polymorphisms in the TLR3 rs3775291, TLR4 rs4986790, TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084, and TLR10 rs4129009 genes. The gene polymorphisms were studied at the age of 6.4 years (mean) in 135 children hospitalised for bronchiolitis in infancy. The outcome measure was current or previous asthma. Current asthma was more common (30%) in children with the variant AG or GG genotype in the TLR10 rs4129009 gene versus those who were homozygous for the major allele A (11%) (p = 0...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28582454/insights-on-the-mechanism-of-action-of-immunostimulants-in-relation-to-their-pharmacological-potency-the-effects-of-imidazoquinolines-on-tlr8
#3
Carlos Kubli-Garfias, Ricardo Vázquez-Ramírez, Cynthia Trejo-Muñoz, Arturo Berber
Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1...
2017: PloS One
https://www.readbyqxmd.com/read/28576825/identification-of-an-optimized-2-o-methylated-tri-nucleotide-rna-motif-inhibiting-toll-like-receptor-7-and-8
#4
Felix C F Schmitt, Isabel Freund, Markus A Weigand, Mark Helm, Alexander H Dalpke, Tatjana Eigenbrod
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic as compared to eukaryotic RNA allow innate immune cells to discriminate between 'host' and 'foreign' RNA. Ribose 2'-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-O-methylation has to occur to mediate its inhibitory activity remains largely undefined...
June 2, 2017: RNA
https://www.readbyqxmd.com/read/28571545/potential-medications-or-compounds-acting-on-toll-like-receptors-in-cerebral-ischemia
#5
Man Li, Jing Liu, Ying Bi, Jixiang Chen, Lei Zhao
Toll-like receptors have been suggested to play an integral role in the process of inflammatory response after ischemic injury. Of all 9 TLRs presenting in brain, functions of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 have been studied in recent years. The MyD88 pathway and TIR domain-containing adaptor inducing interferon pathway are involved in these pathophysiological changes. Since the important role, the therapeutic potential of strategies acting on TLRs should be evaluated. Feasible approaches may function in the following respects, methods acting on TLRs directly, modulations of MyD88 or TRIF signaling pathway, and the ischemic tolerance induced by the preconditioning or postconditioning with TLR ligands or minor cerebral ischemia...
June 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28565836/the-immune-mechanism-of-intestinal-tract-toll-like-receptor-in-mediating-ev71-virus-type-severe-hand-foot-and-mouth-disease-and-the-mapk-pathway
#6
Lei Zhu, Weihua Li, Gongjian Qi, Na Liu, Liping Sheng, Lei Shang, Boxiang Qi
Immunological response is thought to play a crucial role in the development of a severe hand-foot-and-mouth disease (HFMD) infection in children, but the mechanisms remain largely unknown. This study was designed to help in elucidating the immunopathological pathways involved in the disease by quantifying Toll-like receptor (TLR) mRNAs, MAPK factors and cytokine levels in children experiencing the disease. A total of 86 enterovirus 71 (EV71)-infected HFMD children (49 with mild and 27 with severe disease), along with 30 healthy children were involved in the study...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#7
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
May 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28544689/class-ii-obese-and-healthy-pregnant-controls-exhibit-indistinguishable-pro-and-anti-inflammatory-immune-responses-to-caesarian-section
#8
Caroline Graham, Mullein Thorleifson, William P Stefura, Duane J Funk, Kent T HayGlass
INTRODUCTION: Obesity during pregnancy is associated with meta-inflammation and an increased likelihood of clinical complications. Surgery results in intense, acute inflammatory responses in any individual. Because obese individuals exhibit constitutive inflammatory responses and high rates of Caesarian section, it is important to understand the impact of surgery in such populations. Whether more pronounced pro-inflammatory cytokine responses and/or counterbalancing changes in anti-inflammatory immune modulators occurs is unknown...
May 25, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28530246/short-single-stranded-dna-degradation-products-augment-the-activation-of-toll-like-receptor-9
#9
Jelka Pohar, Duško Lainšček, Karolina Ivičak-Kocjan, Miša-Mojca Cajnko, Roman Jerala, Mojca Benčina
Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28500073/fc%C3%AE-riiia-signaling-modulates-endosomal-tlr-responses-in-human-cd4-t-cells
#10
Anil K Chauhan
Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). We show that in CD4(+) T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28495399/evaluation-of-toll-like-receptor-gene-family-variants-as-prognostic-biomarkers-in-rheumatoid-arthritis
#11
Silvia Torices, Lorena Alvarez-Rodríguez, Ignacio Varela, Pedro Muñoz, Alejandro Balsa, M López-Hoyos, Víctor Martinez-Taboada, Jose L Fernández-Luna
Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses, and influence the activity of NFκB, a key player in chronic inflammation. We aimed at investigating the association of TLR allelic variants with susceptibility and severity of RA through a systematic, high-throughput, analysis of TLR genes. All coding exons and flanking regions of nine members of the TLR family (TLR1-9) were analyzed in 66 patients with RA and 30 healthy controls by next generation sequencing...
May 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28472897/the-anticancer-effect-of-mebendazole-may-be-due-to-m1-monocyte-macrophage-activation-via-erk1-2-and-tlr8-dependent-inflammasome-activation
#12
Kristin Blom, Wojciech Senkowski, Malin Jarvius, Malin Berglund, Jenny Rubin, Lena Lenhammar, Vendela Parrow, Claes Andersson, Angelica Loskog, Mårten Fryknäs, Peter Nygren, Rolf Larsson
Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation...
May 4, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#13
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28403045/polymorphisms-of-mannose-binding-lectin-and-toll-like-receptors-2-3-4-7-and-8-and-the-risk-of-respiratory-infections-and-acute-otitis-media-in-children
#14
Laura Toivonen, Juho Vuononvirta, Jussi Mertsola, Matti Waris, Qiushui He, Ville Peltola
BACKGROUND: Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are important components of the innate immune system. We assessed the susceptibility of children with genetic variants in these factors to respiratory infections, rhinovirus infections and acute otitis media. METHODS: In a prospective cohort study, blood samples from 381 Finnish children were analyzed for polymorphisms in MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly, TLR7 Gln11Leu and TLR8 Leu651Leu...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28392469/susceptibility-and-initial-immune-response-of-tupaia-belangeri-cells-to-dengue-virus-infection
#15
Mohammad Enamul Hoque Kayesh, Bouchra Kitab, Takahiro Sanada, Daisuke Hayasaka, Kouichi Morita, Michinori Kohara, Kyoko Tsukiyama-Kohara
Dengue is an emerging disease of great public health significance worldwide. The lack of a suitable infection model has hampered dengue virus (DENV) pathogenesis study, and developing a suitable small animal model has been a long-standing challenge. The aim of this study was to develop a feasible experimental model of DENV infection using Tupaia belangeri. The susceptibility of tupaia to DENV infection and characteristics of its innate immune response were examined in vitro. We found that tupaia fibroblast cells support replication of DENV serotypes 1-4 with a linear increase in viral load 24-96h post-infection in both cells and culture supernatants...
April 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28377925/isolation-of-mesenchymal-stem-cells-from-human-deciduous-teeth-pulp
#16
Aileen I Tsai, Hsiang-Hsi Hong, Wey-Ran Lin, Jen-Fen Fu, Chih-Chun Chang, I-Kuan Wang, Wen-Hung Huang, Cheng-Hao Weng, Ching-Wei Hsu, Tzung-Hai Yen
This study aimed to identify predictors of success rate of mesenchymal stem cell (MSC) isolation from human deciduous teeth pulp. A total of 161 deciduous teeth were extracted at the dental clinic of Chang Gung Memorial Hospital. The MSCs were isolated from dental pulps using a standard protocol. In total, 128 colonies of MSCs were obtained and the success rate was 79.5%. Compared to teeth not yielding MSCs successfully, those successfully yielding MSCs were found to have less severe dental caries (no/mild-to-moderate/severe: 63...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28374903/rna-sensors-of-the-innate-immune-system-and-their-detection-of-pathogens
#17
REVIEW
Nanhua Chen, Pengpeng Xia, Shuangjie Li, Tangjie Zhang, Tony T Wang, Jianzhong Zhu
The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections...
May 2017: IUBMB Life
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#18
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28339016/paeonol-ameliorates-imiquimod-induced-psoriasis-like-skin-lesions-in-balb-c-mice-by-inhibiting-the-maturation-and-activation-of-dendritic-cells
#19
Yujiao Meng, Mingxing Wang, Xiangjiang Xie, Tingting Di, Jingxia Zhao, Yan Lin, Xiaolong Xu, Ningfei Li, Yating Zhai, Yan Wang, Ping Li
Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll‑like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#20
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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