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https://www.readbyqxmd.com/read/27923447/amelioration-of-non-alcoholic-fatty-liver-disease-with-npc1l1-targeted-igy-or-n-3-polyunsaturated-fatty-acids-in-mice
#1
Jin-Sik Bae, Jong-Min Park, Junghoon Lee, Byung-Chul Oh, Sang-Ho Jang, Yun Bin Lee, Young-Min Han, Chan-Young Ock, Ji-Young Cha, Ki-Baik Hahm
Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk for progression to hepatocellular carcinoma in addition to comorbidities such as cardiovascular and serious metabolic diseases; however, the current therapeutic options are limited. Based on our previous report that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can significantly ameliorate high fat diet (HFD)-induced NAFLD, we explored the therapeutic efficacy of n-3 PUFAs and N-IgY, which is a chicken egg yolk-derived IgY specific for the Niemann-Pick C1-Like 1 (NPC1L1) cholesterol transporter, on NAFLD in mice...
January 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#2
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27895422/genetic-polymorphism-in-cd14-gene-a-co-receptor-of-tlr4-associated-with-non-alcoholic-fatty-liver-disease
#3
Shweta Kapil, Ajay Duseja, Bal Krishan Sharma, Bhupesh Singla, Anuradha Chakraborti, Ashim Das, Pallab Ray, Radha K Dhiman, Yogesh Chawla
AIM: To evaluate the pathogenic role of toll-like receptor (TLR) gene polymorphisms in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Two hundred and fifty subjects (NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2 (TLR2) gene (A753G), two polymorphisms in the TLR4 gene (TLR4 Asp299Gly and Thr399Ile allele), and two polymorphisms in the cluster of differentiation 14 (CD14) (C-159T and C-550T) gene, a co-receptor of TLR4...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27875107/the-effect-of-elevated-intra-abdominal-pressure-on-tlr4-signaling-in-intestinal-mucosa-and-on-intestinal-bacterial-translocation-in-a-rat
#4
Adam Strier, Dragan Kravarusic, Arnold G Coran, Isaac Srugo, Nir Bitterman, Tatiana Dorfman, Yulia Pollak, Ibrahim Matter, Igor Sukhotnik
BACKGROUND: Recent evidence suggests that elevated intra-abdominal pressure (IAP) may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR-4) is responsible for the recognition of bacterial endotoxin or lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome. The objective of the current study was to determine the effects of elevated IAP on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to one of two experimental groups: sham animals (Sham) and IAP animals who were subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes...
November 22, 2016: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/27857173/endotoxemia-contributes-to-cd27-memory-b-cell-apoptosis-via-enhanced-sensitivity-to-fas-ligation-in-patients-with-cirrhosis
#5
Li-Yuan Chang, Yonghai Li, David E Kaplan
Peripheral CD27(+) memory B-cells become quantitatively reduced and dysfunctional in patients with cirrhosis through poorly characterized mechanisms. We hypothesized that the disappearance of CD27(+) memory B-cells results from enhanced sensitivity to apoptosis caused by exposure to gut microbial translocation products. Using isolated naïve and memory B-cells from patients with cirrhosis and age-matched controls, ex vivo and activation-induced sensitivity to Fas-mediated apoptosis was assessed under relevant experimental conditions...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27834881/salidroside-regulates-inflammatory-response-in-raw-264-7-macrophages-via-tlr4-tak1-and-ameliorates-inflammation-in-alcohol-binge-drinking-induced-liver-injury
#6
Peng Sun, Shun-Zong Song, Shuang Jiang, Xia Li, You-Li Yao, Yan-Ling Wu, Li-Hua Lian, Ji-Xing Nan
The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS...
November 9, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27830004/ferulic-acid-attenuated-acetaminophen-induced-hepatotoxicity-though-down-regulating-the-cytochrome-p-2e1-and-inhibiting-toll-like-receptor-4-signaling-mediated-inflammation-in-mice
#7
Junhui Yuan, Kuang Ge, Junhuan Mu, Jiang Rong, Li Zhang, Bin Wang, Jingyuan Wan, Gong Xia
Ferulic acid (FA), a phenolic acid which is abundant in vegetables and fruits, has been reported to exert anti-oxidative and anti-inflammatory activities. In the present study, the pharmacological effects and the underlying mechanisms of FA in mice with acetaminophen-induced hepatotoxicity were investigated. Our results revealed that FA pretreatment inhibited the augments of serum aminotransferases in a dose-dependent manner and attenuated the hepatic histopathological abnormalities and hepatocellular apoptosis in acetaminophen (APAP) exposed mice...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27810900/endoplasmic-reticulum-stress-induced-hepatocellular-death-pathways-mediate-liver-injury-and-fibrosis-via-stimulator-of-interferon-genes
#8
Arvin Iracheta-Vellve, Jan Petrasek, Benedek Gyongyosi, Abhishek Satishchandran, Patrick Lowe, Karen Kodys, Donna Catalano, Charles D Calenda, Evelyn A Kurt-Jones, Katherine A Fitzgerald, Gyongyi Szabo
Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING)...
November 3, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27807703/the-critical-role-of-abcg1-and-ppar%C3%AE-lxr%C3%AE-signaling-in-tlr4-mediates-inflammatory-responses-and-lipid-accumulation-in-vascular-smooth-muscle-cells
#9
Xiaojie Cao, Lili Zhang, Chunhai Chen, Qingsong Wang, Lu Guo, Qinlong Ma, Ping Deng, Gang Zhu, Binghu Li, Yan Pi, Chunyan Long, Lei Zhang, Zhengping Yu, Zhou Zhou, Jingcheng Li
Toll-like receptor 4 (TLR4) plays critical roles in vascular inflammation, lipid accumulation and atherosclerosis development. However, the mechanisms underlying these processes are still not well established, especially in vascular smooth muscle cells (VSMCs). ATP-binding cassette transporter G1 (ABCG1) is one of the key genes mediating inflammation and cellular lipid accumulation. The function of TLR4 in regulating the expression of ABCG1 and the underlying molecular mechanisms remain to be elucidated. In this study, we cultured VSMCs from the thoracic aortas of mice and treated the cells with 50 μg/ml oxidized low-density lipoprotein (oxLDL) to activate TLR4 signaling...
November 2, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27788822/microrna-182-5p-ameliorates-liver-ischemia-reperfusion-injury-by-suppressing-toll-like-receptor-4
#10
W Jiang, G Liu, W Tang
BACKGROUND: Toll-like receptor 4 (TLR4) has received a lot of attention in studies on ischemia-reperfusion (I/R) injury. TLR4 is one of the target genes for microRNA-182-5p (miR-182-5p)-mediated regulation. In this study, we evaluated the role(s) of miR-182-5p transcriptional regulation in a hepatic I/R injury model in vivo and a lipopolysaccharide (LPS)-induced inflammatory reaction model in vitro. METHODS: The effects of miR-182-5p expression on the transcription and translation of TLR4 and several proinflammatory cytokines in a LPS-induced macrophage model were studied in vitro...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27788674/mesenchymal-stem-cells-improve-mouse-non-heart-beating-liver-graft-survival-by-inhibiting-kupffer-cell-apoptosis-via-tlr4-erk1-2-fas-fasl-caspase3-pathway-regulation
#11
Yang Tian, Jingcheng Wang, Wei Wang, Yuan Ding, Zhongquan Sun, Qiyi Zhang, Yan Wang, Haiyang Xie, Sheng Yan, Shusen Zheng
BACKGROUND: Liver transplantation is the optimal treatment option for end-stage liver disease, but organ shortages dramatically restrict its application. Donation after cardiac death (DCD) is an alternative approach that may expand the donor pool, but it faces challenges such as graft dysfunction, early graft loss, and cholangiopathy. Moreover, DCD liver grafts are no longer eligible for transplantation after their warm ischaemic time exceeds 30 min. Mesenchymal stem cells (MSCs) have been proposed as a promising therapy for treatment of certain liver diseases, but the role of MSCs in DCD liver graft function remains elusive...
October 27, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27784631/structural-and-functional-annotation-of-human-fam26f-a-multifaceted-protein-having-a-critical-role-in-the-immune-system
#12
Uzma Malik, Aneela Javed, Amjad Ali, Kashif Asghar
BACKGROUND: Human immune system is a complex amalgam of a greatly diverse ensemble comprising of various cellular and non-cellular components, including proteins. FAM26F (family with sequence similarity 26, member F) is a relatively recently identified gene reported to play important role in diverse immune responses. Numerous studies have reported FAM26F to be differentially expressed in several viral, bacterial and parasitic infections, in certain pathophysiological conditions such as heart and liver transplantation, and in several cancers...
January 15, 2017: Gene
https://www.readbyqxmd.com/read/27776340/babao-dan-attenuates-hepatic-fibrosis-by-inhibiting-hepatic-stellate-cells-activation-and-proliferation-via-tlr4-signaling-pathway
#13
Lei Liang, Xue Yang, Yang Yu, Xiaoyong Li, Yechen Wu, Rongyu Shi, Jinghua Jiang, Lu Gao, Fei Ye, Qiudong Zhao, Rong Li, Lixin Wei, Zhipeng Han
Babao Dan (BBD), a traditional Chinese medicine, has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the protective effect of BBD on rat hepatic fibrosis induced by diethylnitrosamine (DEN) and explore it possible mechanism. BBD was administrated while DEN was given. After eight weeks, values of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) indicated that BBD significantly protected liver from damaging by DEN and had no obvious side effect on normal rat livers...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27769711/esculetin-prevents-non-alcoholic-fatty-liver-in-diabetic-mice-fed-high-fat-diet
#14
Ra-Yeong Choi, Ju Ri Ham, Mi-Kyung Lee
This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Plpp2) and inflammation genes (Tlr4, Myd88, Nfkb, Tnfα and Il6)...
December 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27752144/lps-tlr4-pathway-mediates-ductular-cell-expansion-in-alcoholic-hepatitis
#15
Gemma Odena, Jiegen Chen, Juan Jose Lozano, Jose Altamirano, Daniel Rodrigo-Torres, Silvia Affo, Oriol Morales-Ibanez, Hiroshi Matsushita, Jian Zou, Raluca Dumitru, Juan Caballeria, Pere Gines, Vicente Arroyo, Min You, Pierre-Emmanuel Rautou, Dominique Valla, Fulton Crews, Ekihiro Seki, Pau Sancho-Bru, Ramon Bataller
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27744729/epigallocatechin-3-gallate-prevents-triptolide-induced-hepatic-injury-by-restoring-the-th17-treg-balance-in-mice
#16
Shu-Jing Yu, Rong Jiang, Ying Z Mazzu, Cai-Bing Wei, Zong-Liang Sun, Yu-Zhen Zhang, Lian-Di Zhou, Qi-Hui Zhang
Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27737730/spatiotemporal-expression-profile-of-proteases-and-immunological-angiogenic-hormonal-and-apoptotic-mediators-in-rat-placenta-before-and-during-intrauterine-trophoblast-migration
#17
Juneo F Silva, Natália M Ocarino, Rogéria Serakides
The gene and/or protein expression of proteases and immunological, angiogenic, hormonal and apoptotic mediators was evaluated in rat placenta before and during intrauterine trophoblast migration. The depth of interstitial and endovascular intrauterine trophoblast invasion and the immunohistochemical expression of vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk1), interferon (IFN)-γ, migration inhibitory factor (MIF), and inducible nitric oxide synthase (iNOS; also known as nitric oxide synthase (NOS) 2) were evaluated...
October 14, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27685793/tak-242-treatment-ameliorates-liver-ischemia-reperfusion-injury-by-inhibiting-tlr4-signaling-pathway-in-a-swine-model-of-maastricht-category-iii-cardiac-death
#18
Zigong Shao, Baoping Jiao, Tingting Liu, Ying Cheng, Hao Liu, Yongfeng Liu
OBJECTIVES: This study aims to test the effects of TAK-242 on liver transplant viability in a model of swine Maastricht-category-III cardiac death. METHODS: A swine DCD Maastricht-III model of cardiac death was established, and TAK-242 was administered prior to the induction of cardiac death. The protein and mRNA level of TLR4 signaling pathway molecules and cytokines that are important in mediating immune and inflammatory responses were assessed at different time points following the induction of cardiac death...
September 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27677221/puerarin-exerts-the-protective-effect-against-chemical-induced-dysmetabolism-in-rats
#19
Rong Li, Jianhua Song, Wei Wu, Xinmou Wu, Min Su
In this study, we aim to explore the potential benefits of puerarin on metabolic function of liver fibrosis (LF) rat induced by carbon tetrachloride (CCl4), and to investigate with the underlying molecular mechanism targeted on liver and pancreas tissues. In methodology, The LF rats were prepared through intragastrically giving CCl4 twice each week (2ml/kg, v/w) for 8weeks, and dosed puerarin (20, 40mg/kg) were given three times each week via intraperitoneal injection. After being conducted with oral glucose tolerance test (OGTT), the blood samples of rat were harvested for biochemical tests, as well as the liver and pancreas were isolated for histological examination and biochemical assays...
September 24, 2016: Gene
https://www.readbyqxmd.com/read/27676640/ethanol-and-high-cholesterol-diet-causes-severe-steatohepatitis-and-early-liver-fibrosis-in-mice
#20
Yasodha Krishnasamy, Venkat K Ramshesh, Monika Gooz, Rick G Schnellmann, John J Lemasters, Zhi Zhong
BACKGROUND AND AIM: Because ethanol consumption is commonly associated with a high cholesterol diet, we examined whether combined consumption of ethanol and high cholesterol increases liver injury and fibrosis. METHODS: Male C57BL/6J mice were fed diets containing: 1) 35% of calories from corn oil (CTR), 2) CTR plus 0.5% (w/v) cholesterol (Chol), 3) CTR plus ethanol (27% of calories) (EtOH), or 4) EtOH+Chol for 3 months. RESULTS: In mice fed Chol or EtOH alone, ALT increased to ~160 U/L, moderate hepatic steatosis occurred, and leukocyte infiltration, necrosis, and apoptosis increased modestly, but no observable fibrosis developed...
2016: PloS One
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