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https://www.readbyqxmd.com/read/29156826/protective-effect-of-ginkgo-biloba-leaves-extract-egb761-on-myocardium-injury-in-ischemia-reperfusion-rats-via-regulation-of-tlr-4-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Yuping Tang, Guisheng Zhou, Lijun Yao, Ping Xue, Danhong Yu, Renjie Xu, Wen Shi, Xin Yao, Zhaowei Yan, Jin-Ao Duan
Beneficial actions of EGb 761 against ischemia/reperfusion (I/R) injury in lung, brain and renal ischemia have been described. However, the relationship between EGb 761 and signal molecules in myocardial ischemia reperfusion has not been well elucidated. In this study, we investigated the effects and mechanism of EGb 761 preconditioning on anti-myocardial I/R injuries in vivo. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Hemodynamic parameters were monitored as left ventricular systolic pressure, LV end-diastolic pressure and maximal rate of increase and decrease of left ventricular pressure (dP/dtmax)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156775/monophosphoryl-lipid-a-attenuates-radiation-injury-through-tlr4-activation
#2
Jiaming Guo, Yuanyuan Chen, Xiao Lei, Yang Xu, Zhe Liu, Jianming Cai, Fu Gao, Yanyong Yang
Ionizing radiation causes severe damage to human body, and normal tissue toxicity in cancer radiotherapy also limits its further application. It is urgently required to develop safe and effective radioprotector. Our previous study has shown that toll like receptor 4 (TLR4) was dispensable for basal radiation resistance. However, severe toxicity of its traditional agonist lipopolysaccharide limits the clinical application. In present study, we demonstrated that monophosphoryl lipid A (MPLA), a potent TLR4 agonist with low toxicity, effectively attenuated radiation injury on in vitro and in vivo...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156529/alpinetin-improved-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-nafld-through-improving-oxidative-stress-inflammatory-response-and-lipid-metabolism
#3
Yong Zhou, Yin-Lu Ding, Jian-Liang Zhang, Peng Zhang, Jin-Qing Wang, Zhao-Hua Li
The non-alcoholic fatty liver disease (NAFLD) has become a serious medical problem and an increasing threat to public health. It is characterized by the abnormal fat accumulation in liver without excessive alcohol intake. The concurrent NAFLD might up-regulate the risk of chronic kidney disease as well as the mortality rate. Though various drugs have been investigated to attenuate NAFLD, further study is still necessary to find new therapeutic strategy and to reveal the underlying molecular mechanism. In the present study, NAFLD animal models were induced by feeding with high fat (HF) diet for 8 weeks...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156373/mitochondria-targeted-ubiquinone-mitoq-enhances-acetaldehyde-clearance-by-reversing-alcohol-induced-posttranslational-modification-of-aldehyde-dehydrogenase-2-a-molecular-mechanism-of-protection-against-alcoholic-liver-disease
#4
Liuyi Hao, Qian Sun, Wei Zhong, Wenliang Zhang, Xinguo Sun, Zhanxiang Zhou
Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD(+) and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD...
November 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/29155869/nf-%C3%AE%C2%BAb-pathways-are-involved-in-m1-polarization-of-raw-264-7-macrophage-by-polyporus-polysaccharide-in-the-tumor-microenvironment
#5
Chun-Ping Liu, Xian Zhang, Qing-Long Tan, Wen-Xing Xu, Chang-Yuan Zhou, Min Luo, Xiong Li, Run-Yue Huang, Xing Zeng
Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86...
2017: PloS One
https://www.readbyqxmd.com/read/29155428/small-molecule-inhibition-of-tlr8-through-stabilization-of-its-resting-state
#6
Shuting Zhang, Zhenyi Hu, Hiromi Tanji, Shuangshuang Jiang, Nabanita Das, Jing Li, Kentaro Sakaniwa, Jin Jin, Yanyan Bian, Umeharu Ohto, Toshiyuki Shimizu, Hang Yin
Endosomal Toll-like receptors (TLR3, TLR7, TLR8, and TLR9) are highly analogous sensors for various viral or bacterial RNA and DNA molecular patterns. Nonetheless, few small molecules can selectively modulate these TLRs. In this manuscript, we identified the first human TLR8-specific small-molecule antagonists via a novel inhibition mechanism. Crystal structures of two distinct TLR8-ligand complexes validated a unique binding site on the protein-protein interface of the TLR8 homodimer. Upon binding to this new site, the small-molecule ligands stabilize the preformed TLR8 dimer in its resting state, preventing activation...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29155256/role-of-toll-like-receptors-in-inflammatory-bowel-disease
#7
REVIEW
Nastaran Kordjazy, Arvin Haj-Mirzaian, Arya Haj-Mirzaian, Mohammad Mojtaba Rohani, Erwin W Gelfand, Nima Rezaei, Amir Hossein Abdolghaffari
Inflammatory bowel disease (IBD) is the chronic inflammation of the gastrointestinal tract. Recently, studies of the interplay between the adaptive and innate immune responses have provided a better understanding of the immunopathogenesis of inflammatory disorders such as IBD, as well as identification of novel targets for more potent interventions. Toll-like receptors (TLRs) are a class of proteins that play a significant role in the innate immune system and are involved in inflammatory processes. Activation of TLR signal transduction pathways lead to the induction of numerous genes that function in host defense, including those for inflammatory cytokines, chemokines, and antigen presenting molecules...
November 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29155198/immunomodulating-activity-of-the-polysaccharide-tlh-3from-tricholomalobayense-in-raw264-7-macrophages
#8
Mingzhu Zhang, Xiaohe Tian, Ya Wang, Dandan Wang, Wan Li, Lei Chen, Wenjun Pan, Shomaila Mehmood, Yan Chen
Polysaccharide TLH-3 extracted from Tricholoma lobayense possessed unique antioxidant and anti-aging activities, whereas its immunomodulatory properties remain unexplored. Herein in order to explore TLH-3 biological activities, the immunomodulatory effects on RAW264.7 macrophages and its molecular mechanisms were investigated. It was showed that TLH-3 could significantly enhance the phagocytic activity, releasing toxic molecules NO (nitricoxide), secretion of the cytokine TNF-?(tumor necrosis factor-?, IL-6 (interleukin-6)...
November 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29154742/variation-in-the-toll-like-receptor-4-tlr4-gene-affects-milk-traits-in-dairy-cows
#9
Huitong Zhou, Long Cheng, Hua Gong, Seung O Byun, Grant R Edwards, Jon G H Hickford
The objective of this Research Communication was to use polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analysis to investigate a region of the bovine TLR4 gene (TLR4) in pasture-fed New Zealand (NZ) Holstein-Friesian × Jersey (HF × J) cross dairy cows and to determine whether gene variation was associated with milk production traits. Genetic variation was observed, with two variants (A and B) containing a single nucleotide polymorphism (SNP) (c.2021C/T) that was non-synonymous and putatively results in a p...
November 2017: Journal of Dairy Research
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#10
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αMβ2, but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b(-/-) microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47(phox) and superoxide production...
November 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/29153518/subacute-ruminal-acidosis-affects-fermentation-and-endotoxin-concentration-in-the-rumen-and-relative-expression-of-the-cd14-tlr4-md2-genes-involved-in-lipopolysaccharide-systemic-immune-response-in-dairy-cows
#11
B Stefanska, W Człapa, E Pruszynska-Oszmałek, D Szczepankiewicz, V Fievez, J Komisarek, K Stajek, W Nowak
The first objective of this study was to investigate the effects of subacute ruminal acidosis (SARA) on fermentation, ruminal free lipopolysaccharides (LPS), and expression of the cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4), and myeloid differentiation protein 2 (MD2) complex in white blood cells involved in the systemic immune response in dairy cows. The second objective was a study of whether increased expression of the LPS receptor complex led to increases in the concentrations of plasma high-density lipoprotein (HDL) and serum Ca...
November 15, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29153057/sex-dependent-influence-of-developmental-toxicant-exposure-on-group-b-streptococcus-mediated-preterm-birth-in-a-murine-model
#12
Tianbing Ding, Lauren A Lambert, David M Aronoff, Kevin G Osteen, Kaylon L Bruner-Tran
Infectious agents are a significant risk factor for preterm birth (PTB); however, the simple presence of bacteria is not sufficient to induce PTB in most women. Human and animal data suggest that environmental toxicant exposures may act in concert with other risk factors to promote PTB. Supporting this "second hit" hypothesis, we previously demonstrated exposure of fetal mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to an increased risk of spontaneous and infection-mediated PTB in adult animals...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29152585/total-lipopolysaccharide-from-the-human-gut-microbiome-silences-toll-like-receptor-signaling
#13
Eva d'Hennezel, Sahar Abubucker, Leon O Murphy, Thomas W Cullen
Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology...
November 2017: MSystems
https://www.readbyqxmd.com/read/29152559/fasciola-hepatica-esps-could-indistinctly-activate-or-block-multiple-toll-like-receptors-in-a-human-monocyte-cell-line
#14
Olgary Figueroa-Santiago, Ana M Espino
Fasciola hepatica is a parasitic helminth that induces Th2/Treg responses in its mammalian host. Some reports have suggested that ESPs achieve these polarized immune responses by delaying the activation of dendritic cells and macrophages during the early stages of innate immunity, a process that is mediated by TLR4. The present study aimed to investigate whether TLRs other than TLR4 could also be targeted by F. hepatica ESPs. To achieve this aim a screening system was optimized using THP1-Blue CD14 cells. ESPs were first separated based on their molecular weight and according their net charge by ion exchange chromatography (IEC)...
2017: Ann Clin Pathol
https://www.readbyqxmd.com/read/29152461/use-of-toll-like-receptor-assays-for-the-detection-of-bacterial-contaminations-in-icodextrin-batches-released-for-peritoneal-dialysis
#15
Hêla Hacine-Gherbi, Agnès Denys, Mathieu Carpentier, Arnaud Heysen, Pierrick Duflot, Pierre Lanos, Fabrice Allain
Icodextrin is a starch derivative used for preparing solutions of peritoneal dialysis. Unfortunately, peptidoglycans (PGN) and lipopolysaccharides (LPS) have been reported to contaminate certain icodextrin batches and to contribute to the development of sterile peritonitis. The decision of selecting or rejecting icodextrin batches is however difficult, because of limitations in the detection of these bacterial contaminants. Besides monocyte activation tests of cytokine release, a number of bio-assays using stably TLR-transfected cell lines have been developed...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/29152245/metabolic-syndrome-and-inflammation-in-adipose-tissue-occur-at-different-times-in-animals-submitted-to-a-high-sugar-fat-diet
#16
Fabiane Valentini Francisqueti, André Ferreira Nascimento, Igor Otávio Minatel, Marcos Correa Dias, Renata de Azevedo Melo Luvizotto, Carolina Berchieri-Ronchi, Ana Lúcia A Ferreira, Camila Renata Corrêa
Obesity is associated with low-grade inflammation, triggered in adipose tissue, which may occur due to an excess of SFA from the diet that can be recognised by Toll-like receptor-4. This condition is involved in the development of components of the metabolic syndrome associated with obesity, especially insulin resistance. The aim of the study was to evaluate the manifestation of the metabolic syndrome and adipose tissue inflammation as a function of the period of time in which rats were submitted to a high-sugar/fat diet (HSF)...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29152046/design-and-synthesis-of-n1-modified-imidazoquinoline-agonists-for-selective-activation-of-toll-like-receptors-7-and-8
#17
Peter Larson, Tamara A Kucaba, Zhengming Xiong, Michael Olin, Thomas S Griffith, David M Ferguson
A series of N1-modified imidazoquinolines were synthesized and screened for Toll-like receptors (TLR) 7 and 8 activities to identify recognition elements that confer high affinity binding and selectivity. These receptors are key targets in the development of immunomodulatory agents that signal the NF-κB mediated transcription of pro-inflammatory chemokines and cytokines. Results are presented showing both TLR7/8 activations are highly correlated to N1-substitution, with TLR8 selectivity achieved through inclusion of an ethyl-, propyl-, or butylamino group at this position...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29151895/toll-like-receptor-4-differentially-mediates-intestinal-and-extra-intestinal-immune-responses-upon-multi-drug-resistant-pseudomonas-aeruginosa-association-of-il10-mice-with-chronic-colitis
#18
Anne Grunau, Ulrike Escher, Anja A Kühl, Stefan Bereswill, Markus M Heimesaat
Background: Infections with multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (PA) have become a serious threat particularly in hospitalized patients with immunopathological co-morbidities. The well-balanced interplay between immune cells, pattern recognition receptors such as Toll-like receptor (TLR)-4 sensing lipopolysaccharide from Gram-negative bacteria including PA, and evolving pathways is crucial to prevent the host from invading (opportunistic) pathogens...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/29151033/induction-of-dendritic-cell-mediated-activation-of-t-cells-from-atherosclerotic-plaques-by-human-heat-shock-protein-60
#19
Mizanur Rahman, Johnny Steuer, Peter Gillgren, Assim Hayderi, Anquan Liu, Johan Frostegård
BACKGROUND: Atherosclerosis is characterized by the presence of activated immune-competent cells including dendritic cells (DCs) and T cells, dead cells, and oxidized low-density lipoprotein. HSP60 (Heat shock protein 60) has been implicated in atherosclerosis. A plasma protein, Annexin A5, has atheroprotective properties. METHODS AND RESULTS: Human DCs differentiated from peripheral blood monocytes were treated with human HSP60 or HSP90 and autologous T cells were cocultured with these pretreated DCs (mDCs)...
November 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#20
REVIEW
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Hamid Fiuji, Saman Soleimanpour, Gordon A Ferns, Amir Avan, Majid Khazaei
Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
November 18, 2017: Journal of Cellular Physiology
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