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https://www.readbyqxmd.com/read/28438835/il-1%C3%AE-transcriptionally-activates-hepcidin-by-inducing-c-ebp%C3%AE-expression-in-hepatocytes
#1
Yohei Kanamori, Masaru Murakami, Makoto Sugiyama, Osamu Hashimoto, Tohru Matsui, Masayuki Funaba
Hepcidin is a liver-derived hormone that negatively regulates serum iron levels and is mainly regulated at the transcriptional level. Previous studies have clarified that in addition to hepatic iron levels, inflammation also efficiently increases hepatic hepcidin expression. The principle regions responsible for efficient hepcidin transcription are bone morphogenetic protein-responsive elements (BMP-REs) 1 and 2 as well as the signal transducer and activator of transcription 3-binding site (STAT-BS). Here, we show that the proinflammatory cytokine interleukin-1β (IL-1β) efficiently increases hepcidin expression in human HepG2 liver-derived cells and primary mouse hepatocytes...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28437886/activation-of-imidazoline-i1-receptor-by-moxonidine-regulates-the-progression-of-liver-fibrosis-in-the-nrf2-dependent-pathway
#2
Wenfeng Zhang, Xuanfei Li, Yanmin Liu, Hao Chen, Jianping Gong
Imidazoline I1 receptor (I1R) has been recognized as a promising target in the treatment of many diseases, but little is known about its function in liver fibrogenesis. This study aimed to investigate the effect of I1R activation on the development and progression of liver fibrosis. The results showed that I1R expression was decreased in the livers of both patients and mice with liver fibrosis, and in TGF-β-treated hepatic stellate cells (HSCs). Activation of I1R by moxonidine (MOX) significantly inhibited the progression of liver fibrosis in carbon tetrachloride-induced mice and attenuated the activation of HSCs and kupffer cells...
April 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28427446/respiratory-chain-complex-iii-deficiency-due-to-mutated-bcs1l-a-novel-phenotype-with-encephalomyopathy-partially-phenocopied-in-a-bcs1l-mutant-mouse-model
#3
Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A Eklund, Vineta Fellman
BACKGROUND: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. RESULTS: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology...
April 20, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28427239/foxo3a-dependent-bim-transcription-protects-mice-from-a-high-fat-diet-via-inhibition-of-activation-of-the-nlrp3-inflammasome-by-facilitating-autophagy-flux-in-kupffer-cells
#4
Liu Yan, Zhang Wenfeng, Wu Xiaoling, Gong Jianping
BACKGROUND: The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. RESULTS: Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were significantly changed with the alteration of Foxo3a in KCs under PA and LPS stimulation among foxo3a targeted genes...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423012/15-hydroxyprostaglandin-dehydrogenase-15-pgdh-prevents-lipopolysaccharide-lps-induced-acute-liver-injury
#5
Lu Yao, Weina Chen, Kyoungsub Song, Chang Han, Chandrashekhar R Gandhi, Kyu Lim, Tong Wu
The NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of prostaglandin E2 (PGE2), converting the pro-inflammatory PGE2 to the anti-inflammatory 15-keto-PGE2 (an endogenous ligand for peroxisome proliferator-activated receptor-gamma [PPAR-γ]). To evaluate the significance of 15-PGDH/15-keto-PGE2 cascade in liver inflammation and tissue injury, we generated transgenic mice with targeted expression of 15-PGDH in the liver (15-PGDH Tg) and the animals were subjected to lipopolysaccharide (LPS)/Galactosamine (GalN)-induced acute liver inflammation and injury...
2017: PloS One
https://www.readbyqxmd.com/read/28422200/enhancing-mri-of-liver-metastases-with-a-zwitterionized-biodegradable-dendritic-contrast-agent
#6
Xiaoxuan Zhou, Mingzhou Ye, Yuxin Han, Jianbin Tang, Yue Qian, Hongjie Hu, Youqing Shen
Metastasis is the main reason for cancer-associated mortality, and accurate diagnostic imaging of metastases is critical for the clinical administration and tailoring personalized treatments for metastatic tumors. However, magnetic resonance imaging of metastases in the liver is impeded by its low sensitivity because the currently used contrast agents accumulate in hepatocytes and Kupffer cells instead of cancer cells. Herein, a 4(th) generation zwitterionized biodegradable dendritic contrast agent (DCA) with a size of ca...
April 19, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28420329/contrast-enhanced-us-with-perfluorobutane-sonazoid-used-as-a-surveillance-test-for-hepatocellular-carcinoma-hcc-in-cirrhosis-scan-an-exploratory-cross-sectional-study-for-a-diagnostic-trial
#7
MULTICENTER STUDY
Ji Hoon Park, Mi-Suk Park, So Jung Lee, Woo Kyoung Jeong, Jae Young Lee, Min Jung Park, Kyunghwa Han, Chung Mo Nam, Seong Ho Park, Kyoung Ho Lee
BACKGROUND: Ultrasonography (US) is widely used as a standard surveillance tool for patients who are at a high risk of having hepatocellular carcinoma (HCC); however, conventional B-mode US appears to be insufficient in order to ensure the early detection of HCC. Perfluorobutane allows very stable Kupffer phase imaging for at least 60 min, which is tolerable for examinations of the entire liver. The purpose of our study is to evaluate the added value of contrast-enhanced US using perfluorobutane to that of conventional B-mode US as an HCC surveillance tool for patients with liver cirrhosis...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#8
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28405397/dynamics-of-cilia-length-in-left-right-development
#9
P Pintado, P Sampaio, B Tavares, T D Montenegro-Johnson, D J Smith, S S Lopes
Reduction in the length of motile cilia in the zebrafish left-right organizer (LRO), also known as Kupffer's vesicle, has a large impact on left-right development. Here we demonstrate through genetic overexpression in zebrafish embryos and mathematical modelling that the impact of increased motile cilia length in embryonic LRO fluid flow is milder than that of short cilia. Through Arl13b overexpression, which increases cilia length without impacting cilia beat frequency, we show that the increase in cilium length is associated with a decrease in beat amplitude, resulting in similar flow strengths for Arl13b overexpression and wild-type (WT) embryos, which were not predicted by current theory...
March 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28404639/cholesterol-crystallization-within-hepatocyte-lipid-droplets-and-its-role-in-murine-nash
#10
George N Ioannou, Savitha Subramanian, Alan Chait, W Geoffrey Haigh, Matthew M Yeh, Geoffrey C Farrell, Sum P Lee, Christopher Savard
We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental NASH. Herein, we assigned wild-type C57BL/6J mice to a high-fat (15%) diet for 6 months supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration ≥0.5%, whereas mice on lower cholesterol diets developed only simple steatosis...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28402755/distribution-of-fcrn-across-species-and-tissues
#11
Sari Latvala, Bjoern Jacobsen, Michael B Otteneder, Annika Herrmann, Sven Kronenberg
The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and albumin, thereby protecting them from lysosomal degradation. Therefore, besides the knowledge of FcRn affinity, FcRn protein expression is critical in understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such as monoclonal antibodies. The goal of this investigation was to achieve for the first time a comparative assessment of FcRn distribution across a variety of tissues and species...
April 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28393189/upregulation-of-heme-oxygenase-1-in-kupffer-cells-blocks-mast-cell-degranulation-and-inhibits-dendritic-cell-migration-in%C3%A2-vitro
#12
Yuan-Yuan Ma, Mu-Qing Yang, Zhi-Gang He, Mao-Hong Fan, Man Huang, Fei Teng, Qing Wei, Ji-Yu Li
Kupffer cells (KCs) influence liver allografts by interacting with other non‑parenchymal cells. However, the exact mechanism remains unclear. Upregulation of heme oxygenase-1 (HO-1) in KCs upon interaction with mast cells (MCs), and the effects on dendritic cell (DC) function, were investigated in the present study. KCs, MCs and DCs were prepared from 8‑10‑week‑old C57BL/6 mice. KCs were pretreated with PBS, dimethyl sulfoxide, hemin (50 µM; HO‑1 inducer), and zinc protoporphyrin (50 µM; HO‑1 inhibitor) for 8 h...
April 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28390947/expression-patterns-of-nuclear-receptors-in-parenchymal-and-non-parenchymal-mouse-liver-cells-and-their-modulation-in-cholestasis
#13
Ester Gonzalez-Sanchez, Delphine Firrincieli, Chantal Housset, Nicolas Chignard
Nuclear receptors (NR), the largest family of transcription factors, control many physiological and pathological processes. To gain insight into hepatic NR and their potential as therapeutic targets in cholestatis, we determined their expression in individual cell types of the mouse liver in normal and cholestatic conditions. Hepatocytes, cholangiocytes, hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were isolated from the liver of mice with acute or chronic cholestasis (i...
April 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28390933/effects-of-dietary-resveratrol-supplementation-on-hepatic-and-serum-pro-anti-inflammatory-activity-in-juvenile-gift-tilapia-oreochromis-niloticus
#14
Yao Zheng, Zhixiang Zhao, Wei Wu, Chao Song, Shunlong Meng, Limin Fan, Xuwen Bing, Jiazhang Chen
Dietary resveratrol (RES) supplementation may have some pharmacological effects including anti-inflammation. Previous studies have shown that Kupffer cell activation and apoptosis induction increases the transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities of 0.1 or 0.3 g/kg RES as a dietary supplement in juvenile freshwater tilapia (Oreochromis niloticus). The results showed that hepatic and serum immunoglobulin M (IgM) significantly decreased and increased while anti- and pro-inflammatory cytokines significantly increased and decreased, respectively, in the RES-treated groups...
April 5, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28386259/elevated-expression-of-chemokine-cxcl13-in-chronic-hepatitis-b-patients-links-to-immune-control-during-antiviral-therapy
#15
Chao Liu, Xuan Huang, Melanie Werner, Ruth Broering, Jun Ge, Yongyin Li, Baolin Liao, Jian Sun, Jie Peng, Mengji Lu, Jinlin Hou, Xiaoyong Zhang
C-X-C-chemokine ligand 13 (CXCL13), the ligand for C-X-C chemokine receptor type 5 (CXCR5), is a major regulator of B-cell trafficking and plays an integral role in age-dependent clearance of hepatitis B virus (HBV) in the mouse model. However, the expression and function of CXCL13 in patients with chronic hepatitis B (CHB) remain unknown. By use of liver cell subpopulations isolated from CHB patients, we found that CXCL13 mRNA was abundantly expressed in Kupffer cells (KCs), but not in primary hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28382855/natural-infections-with-pigeon-paramyxovirus-serotype-1-pathologic-changes-in-eurasian-collared-doves-streptopelia-decaocto-and-rock-pigeons-columba-livia-in-the-united-states
#16
M Isidoro-Ayza, C L Afonso, J B Stanton, S Knowles, H S Ip, C L White, H Fenton, M G Ruder, A C Dolinski, J Lankton
Pigeon paramyxovirus serotype 1 (PPMV-1) is a globally distributed, virulent member of the avian paramyxovirus serotype 1 serogroup that causes mortality in columbiformes and poultry. Following introduction into the United States in the mid-1980s, PPMV-1 rapidly spread causing numerous mortality events in Eurasian collared-doves ( Streptopelia decaocto) (ECDOs) and rock pigeons ( Columba livia) (ROPIs). The investigators reviewed pathological findings of 70 naturally infected, free-ranging columbiforms from 25 different mortality events in the United States...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28382699/washout-ratio-in-the-hepatic-vein-measured-by-contrast-enhanced-ultrasonography-to-distinguish-between-inflammatory-and-noninflammatory-hepatic-disorders-in-dogs
#17
K Morishita, A Hiramoto, A Michishita, S Takagi, T Osuga, S Y Lim, K Nakamura, N Sasaki, H Ohta, M Takiguchi
BACKGROUND: Perflubutane microbubbles, a second-generation ultrasound contrast agent, are phagocytized by Kupffer cells. This characteristic may be useful to differentiate diffuse hepatic diseases in dogs. HYPOTHESIS/OBJECTIVES: To determine whether the washout ratio in the hepatic vein (HV) measured by contrast-enhanced ultrasonography (CEUS) can distinguish between inflammatory and noninflammatory hepatic disorders in dogs. ANIMALS: Forty-one client-owned dogs with hepatic disorders including 14 with hepatitis, 7 with primary hypoplasia of the portal vein (PHPV), 9 with congenital portosystemic shunt (cPSS), and 11 with other hepatopathy were enrolled...
April 5, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28373104/nanocrystal-formulations-of-a-poorly-soluble-drug-2-evaluation-of-nanocrystal-liver-uptake-and-distribution-after-intravenous-administration-to-mice
#18
Kalle Sigfridsson, Pia Skantze, Urban Skantze, Lena Svensson, Lars Löfgren, Pär Nordell, Erik Michaëlsson, Bård Smedsrød, Britt Fuglesteg, Kjetil Elvevold, Lennart Lindfors
A stabilized high drug load intravenous formulation could allow compounds with less optimal pharmacokinetic profiles to be developed. Polyethylene glycol (PEG)-ylation is a frequently used strategy for particle delivery systems to avoid the liver, thereby extending blood circulation time. The present work reports the mouse in vivo distribution after i.v. administration of a series of nanocrystals prepared with the bead milling technique and PEG-ylated with DSPE-PEG2000 and Pluronic F127, with and without polyvinylpyrrolidone K30 (PVP)/Aerosol OT (AOT) as primary stabilizers...
March 31, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28365916/pigment-epithelium-derived-factor-pedf-prevents-hepatic-fat-storage-inflammation-and-fibrosis-in-dietary-steatohepatitis-of-mice
#19
Takafumi Yoshida, Jun Akiba, Takanori Matsui, Kazuo Nakamura, Takao Hisamoto, Mitsuhiko Abe, Yu Ikezono, Fumitaka Wada, Hideki Iwamoto, Toru Nakamura, Hironori Koga, Sho-Ichi Yamagishi, Takuji Torimura
BACKGROUND AND AIMS: Pigment epithelium-derived factor (PEDF) has been shown to be a potent inhibitor of inflammation through its anti-oxidative property. Since oxidative response is considered to play the pivotal role of the development and progression of nonalcoholic steatohepatitis (NASH), it is conceivable that PEDF may play a protective role against NASH. In this study, we examined whether administration of PEDF slowed the progression of NASH in mice models. METHODS: Mice were fed methionine- and choline-deficient (MCD) diet with or without intramuscular administration of adenovirus-expressing PEDF (Ad-PEDF)...
April 1, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28349484/in-vitro-and-ex-vivo-models-to-study-t-cell-migration-through-the-human-liver-parenchyma
#20
Benjamin G Wiggins, Konstantinos Aliazis, Scott P Davies, Gideon Hirschfield, Patricia F Lalor, Gary Reynolds, Zania Stamataki
The liver is the largest internal organ and filters around 3 pints of blood per minute. This continuous flux of blood should not be confused with rapid egress of lymphocytes through the liver; this organ has intricate corridors of specialized sinusoidal spaces, ensuring that immune cells decelerate to shear flow rates, and providing ample opportunities to interact with parenchymal cells. Migration has been intricately linked to T cell function; it is therefore important to study liver T cell biology into context within the liver microenvironment...
2017: Methods in Molecular Biology
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