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https://www.readbyqxmd.com/read/29243365/vitamin-a-coupled-liposome-system-targeting-free-cholesterol-accumulation-in-hepatic-stellate-cells-offers-a-beneficial-therapeutic-strategy-for-liver-fibrosis
#1
Hirotaka Furuhashi, Kengo Tomita, Toshiaki Teratani, Motonori Shimizu, Makoto Nishikawa, Masaaki Higashiyama, Takeshi Takajo, Kazuhiko Shirakabe, Koji Maruta, Yoshikiyo Okada, Chie Kurihara, Chikako Watanabe, Shunsuke Komoto, Suefumi Aosasa, Shigeaki Nagao, Junji Yamamoto, Soichiro Miura, Ryota Hokari
AIM: Liver fibrosis is a life-threatening disorder for which no approved therapy is available. Recently, we reported that mouse hepatic stellate cell (HSC) activation increased free cholesterol (FC) accumulation partly by enhancing signaling via sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-β (TGFβ)-induced activation in a 'vicious cycle' of liver fibrosis. METHODS: Human HSCs were isolated from surgical liver specimens from the control patients and patients with liver fibrosis...
December 15, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29241030/expression-profiles-of-genes-involved-in-tlrs-and-nlrs-signaling-pathways-of-water-buffaloes-infected-with-fasciola-gigantica
#2
Fu-Kai Zhang, Jun-Ling Hou, Ai-Jiang Guo, Ai-Ling Tian, Zhao-An Sheng, Wen-Bin Zheng, Wei-Yi Huang, Hany M Elsheikha, Xing-Quan Zhu
Infection of ruminants and humans with Fasciola gigantica is attracting increasing attention due to its economic impact and public health significance. However, little is known of innate immune responses during F. gigantica infection. Here, we investigated the expression profiles of genes involved in Toll-like receptors (TLRs) and NOD-like receptors (NLRs) signaling pathways in buffaloes infected with 500F. gigantica metacercariae. Serum, liver and peripheral blood mononuclear cell (PBMC) samples were collected from infected and control buffaloes at 3, 10, 28, and 70days post infection (dpi)...
December 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29235260/functional-polymorphisms-of-innate-immunity-receptors-are-not-risk-factors-for-the-non-sbp-type-bacterial-infections-in-cirrhosis
#3
Tamas Dinya, Tamas Tornai, Zsuzsanna Vitalis, Istvan Tornai, Boglárka Balogh, David Tornai, Peter Antal-Szalmas, Andrea Sumegi, Hajnalka Andrikovics, Andras Bors, Attila Tordai, Maria Papp
BACKGROUND&AIMS: Pattern recognition receptors (PRRs) have a key role in the innate host defense. Functional polymorphisms of various PRRs have been established to contribute to an increased susceptibility to spontaneous bacterial peritonitis (SBP). Their role in the development of cirrhosis-associated bacterial infections (BI), beyond SBP or progressive disease course related to pathological bacterial translocation (BT) remains unknown. METHODS: 349 patients with cirrhosis were genotyped for common NOD2 (R702W, G908R and L1007PfsinsC), TLR2 (-16934T>A), and TLR4 (D299G) variants...
December 13, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29234326/toll-like-receptor-4-on-both-myeloid-cells-and-dendritic-cells-is-required-for-systemic-inflammation-and-organ-damage-after-hemorrhagic-shock-with-tissue-trauma-in-mice
#4
Kent Zettel, Sebastian Korff, Ruben Zamora, Adrian E Morelli, Sophie Darwiche, Patricia A Loughran, Greg Elson, Limin Shang, Susana Salgado-Pires, Melanie J Scott, Yoram Vodovotz, Timothy R Billiar
Trauma combined with hemorrhagic shock (HS/T) leads to systemic inflammation, which results in organ injury. Toll-like Receptor 4 (TLR4)-signaling activation contributes to the initiation of inflammatory pathways following HS/T but its cell-specific roles in this setting are not known. We assessed the importance of TLR4 on leukocytes of myeloid lineage and dendritic cells (DCs) to the early systemic inflammatory response following HS/T. Mice were subjected to HS/T and 20 inflammatory mediators were measured in plasma followed by Dynamic Bayesian Network (DBN) Analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29223854/baicalein-improves-liver-inflammation-in-diabetic-db-db-mice-by-regulating-hmgb1-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Huafeng Yin, Lihao Huang, Ting Ouyang, Lvyi Chen
The current study was designed to investigate the hepatoprotective effects and possible mechanisms of Baicalein (BA) on the diabetic liver injury in vivo and in vitro. The results exhibited that BA significantly restored the blood glucose in oral glucose tolerance test (OGTT) and inhibited the levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) in C57BL/KsJ-db/db mice. Moreover, BA strikingly attenuated the extent of steatosis in the liver tissues of diabetic mice...
December 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29221801/donor-polymorphisms-of-toll-like-receptor-4-rs1927914-associated-with-the-risk-of-hepatocellular-carcinoma-recurrence-following-liver-transplantation
#6
Guangjun Shi, Chuanxu Wang, Ping Zhang, Lisha Ji, Shifeng Xu, Xueying Tan, Hao Li
BACKGROUND: Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) severely restricts the long-term survival of patients. Toll-like receptor 4 (TLR4) has been considered to be involved in hepatocarcinogenesis and metastasis. Additionally, there is a study demonstrating the significant association between TLR4 gene rs1927914 polymorphism and HCC, but no study investigated the association of the TLR4 rs1927914 polymorphism with the risk of HCC recurrence following LT...
December 5, 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/29207664/shikonin-protects-against-d-galactosamine-and-lipopolysaccharide-induced-acute-hepatic-injury-by-inhibiting-tlr4-signaling-pathway
#7
Meng-Xiang Lin, Yong-Xiang Yi, Pei-Pei Fang, Shan-Shan Huang, Chen-Wei Pan, Ling-Xiang Jin, Tong Zhang, Guang-Yao Zhou
Shikonin, a naphthoquinone isolated from the root of medical herb Lithospermum erythrorhizon, has been reported to have anti-inflammatory effect. However, there is no related research for the treatment of shikonin on hepaic injury. The purpose of this study was to investigate the effects of shikonin on D-Galactosamine and Lipopolysaccharide-induced hepatic injury in mice. Male BALB/c mice were pretreated with shikonin 1 h before LPS/D-GalN treatment. The pathological changes of hepatic injury were detected by H&E staining...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203538/high-mobility-group-box-1-orchestrates-tissue-regeneration-via-cxcr4
#8
Mario Tirone, Ngoc Lan Tran, Chiara Ceriotti, Andrea Gorzanelli, Monica Canepari, Roberto Bottinelli, Angela Raucci, Stefania Di Maggio, César Santiago, Mario Mellado, Marielle Saclier, Stéphanie François, Giorgia Careccia, Mingzhu He, Francesco De Marchis, Valentina Conti, Sabrina Ben Larbi, Sylvain Cuvellier, Maura Casalgrandi, Alessandro Preti, Bénédicte Chazaud, Yousef Al-Abed, Graziella Messina, Giovanni Sitia, Silvia Brunelli, Marco Emilio Bianchi, Emilie Vénéreau
Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine. Here we report that fully reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced glycation end products) are not involved...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29199028/sex-dependent-influences-of-morphine-and-its-metabolites-on-pain-sensitivity-in-the-rat
#9
H H Doyle, A Z Murphy
Preclinical studies report that the effective dose for morphine is approximately 2-fold higher in females than males. Following systemic administration, morphine is metabolized via Phase II glucuronidation in the liver and brain into two active metabolites: morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), each possessing distinct pharmacological profiles. M6G binds to μ opioid receptors and acts as a potent analgesic. In contrast, M3G binds to toll-like receptor 4 (TLR4), initiating a neuroinflammatory response that directly opposes the analgesic effects of morphine and M6G...
November 30, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29196051/lycium-barbarum-polysaccharides-improve-ccl4-induced-liver-fibrosis-inflammatory-response-and-tlrs-nf-kb-signaling-pathway-expression-in-wistar-rats
#10
Fang Gan, Qing Liu, Yunhuan Liu, Da Huang, Cuiling Pan, Suquan Song, Kehe Huang
Lycium barbarum polysaccharides (LBPs) have multiple biological and pharmacological functions, including antioxidant, anti-inflammatory and anticancer activities. This research was conducted to evaluate whether LBPs could alleviate carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying signaling pathway mechanism. Fifty male wistar rats were randomly allocated to five groups (n=10): control, CCl4 and CCl4 with 400, 800 or 1600mg/kg LBPs, respectively. Each wistar rat from each group was used for blood and tissue collections at the end of experiment...
November 28, 2017: Life Sciences
https://www.readbyqxmd.com/read/29190550/green-tea-extract-protects-against-hepatic-nf%C3%AE%C2%BAb-activation-along-the-gut-liver-axis-in-diet-induced-obese-mice-with-nonalcoholic-steatohepatitis-by-reducing-endotoxin-and-tlr4-myd88-signaling
#11
Jinhui Li, Geoffrey Y Sasaki, Priyankar Dey, Chureeporn Chitchumroonchokchai, Allison N Labyk, Joshua D McDonald, Joshua B Kim, Richard S Bruno
Green tea extract (GTE) reduces NFκB-mediated inflammation during nonalcoholic steatohepatitis (NASH). We hypothesized that its anti-inflammatory activities would be mediated in a Toll-like receptor 4 (TLR4)-dependent manner. Wild-type (WT) and loss-of-function TLR4-mutant (TLR4m) mice were fed a high-fat diet containing GTE at 0 or 2% for 8 weeks before assessing NASH, NFκB-mediated inflammation, TLR4 and its adaptor proteins MyD88 and TRIF, circulating endotoxin, and intestinal tight junction protein mRNA expression...
November 3, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29186870/dietary-supplementation-with-lactobacillus-casei-alleviates-lipopolysaccharide-induced-liver-injury-in-a-porcine-model
#12
Di Zhao, Tao Wu, Dan Yi, Lei Wang, Peng Li, Junmei Zhang, Yongqing Hou, Guoyao Wu
This study aims to determine whether Lactobacillus casei (L. casei) could relieve liver injury in piglets challenged with lipopolysaccharide (LPS). Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 10⁶ cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight), while the control group received the same volume of saline...
November 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29181417/toll-like-receptor-ligand-induced-liver-injury-in-d-galactosamine-sensitized-mice-differences-between-tlr7-8-and-tlr9-ligands-cytokine-patterns-and-cross-tolerance-induction-by-tlr2-ligand-pretreatment
#13
Reiko Seki
Administration of Toll-like receptor ligands (TLRLs) is known to cause liver injury in D-galN-sensitized mice. In the present study, we aimed to complement preceding reports on the TLRL/D-galN system by analyzing comparisons among TLRLs, mouse strain dependence, effects on serum levels of cytokines, and effects of sequential administrations of different TLRLs. In a preliminary set of analyses, we first confirmed that liver failure can be induced by diverse TLRLs, including LTA and R848 in combination with D-galN...
2017: Journal of Immunology Research
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
#14
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
#15
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/29149705/toll-like-receptor-4-deficiency-increases-resistance-in-sepsis-induced-immune-dysfunction
#16
Chao Cao, Yanfen Chai, Songtao Shou, Jun Wang, Ying Huang, Tao Ma
Sepsis constitutes a serious life-threatening syndrome associated with complications of deregulated inflammatory response against endotoxin/lipopolysaccharide (LPS)-mediated severe infection. Toll-like receptor 4 (TLR4) plays a critical role in the activation of innate immunity through recognition of LPS. However, the impact of TLR4 signaling on the development of sepsis-induced immune dysfunction remains unclear. The aim of this study was to investigate the effect of TLR4 on regulatory T cells (Tregs) and its potential mechanism...
November 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#17
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29138821/protective-effects-of-oxymatrine-against-lipopolysaccharide-d%C3%A2-galactosamine%C3%A2-induced-acute-liver-failure-through-oxidative-damage-via-activation-of-nrf2-ho%C3%A2-1-and-modulation-of-inflammatory-tlr4%C3%A2-signaling-pathways
#18
Jian Xu, Chengmin Li, Ziwei Li, Chan Yang, Lan Lei, Wei Ren, Yan Su, Chunping Chen
Oxymatrine has a variety of pharmacological functions, including anti-viral, anti-liver fibrotic, anti-cancer, anti‑bacterial, anti‑epidemic, analgesic, anti‑allergy and anti‑inflammatory properties. The present study aimed to investigate the protective effects of oxymatrine against lipopolysaccharide (LPS)/D‑galactosamine (D‑GalN)‑induced acute liver failure and the associated underlying mechanisms. Mice were administrated 4 mg/kg LPS and 600 mg/kg D‑GalN. Then, mice in the Oxymatrine group were treated with 120 mg/kg of oxymatrine for 4 weeks...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29127992/leishmania-infantum-exerts-immunomodulation-in-canine-kupffer-cells-reverted-by-meglumine-antimoniate
#19
A Rodrigues, D Santos-Mateus, G Alexandre-Pires, A Valério-Bolas, M Rafael-Fernandes, M A Pereira, D Ligeiro, J de Jesus, R Alves-Azevedo, S Lopes-Ventura, M Santos, A M Tomás, I Pereira da Fonseca, G Santos-Gomes
Kupffer cells (KC) are the liver macrophage population that resides in the hepatic sinusoids and efficiently phagocyte pathogens by establishing an intimate contact with circulating blood. KC constitute the liver host cells in Leishmania infection, nevertheless little is described about their role, apart from their notable contribution in granulomatous inflammation. The present study aims to investigate how canine KC sense and react to the presence of Leishmania infantum promastigotes and amastigotes by evaluating the gene expression of specific innate immune cell receptors and cytokines, as well as the induction of nitric oxide and urea production...
December 2017: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/29115619/administration-of-chlorogenic-acid-alleviates-spinal-cord-injury-via-tlr4-nf%C3%A2-%C3%AE%C2%BAb-and-p38-signaling-pathway-anti%C3%A2-inflammatory-activity
#20
Dayong Chen, Dan Pan, Shaolong Tang, Zhihong Tan, Yanan Zhang, Yunfeng Fu, Guohua Lü, Qinghua Huang
Chlorogenic acid, as a secondary metabolite of plants, exhibits a variety of effects including free radical scavenging, antiseptic, anti‑inflammatory and anti‑viral, in addition to its ability to reduce blood glucose, protect the liver and act as an anti‑hyperlipidemic agent and cholagogue. The present study demonstrated that administration of chlorogenic acid alleviated spinal cord injury (SCI) via anti‑inflammatory activity mediated by nuclear factor (NF)‑κB and p38 signaling pathways. Wistar rats were used to structure a SCI model rat to explore the effects of administration of chlorogenic acid on SCI...
November 6, 2017: Molecular Medicine Reports
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