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https://www.readbyqxmd.com/read/29329095/investigation-of-silver-ag-deposition-in-tissues-from-stranded-cetaceans-by-autometallography-amg
#1
Wen-Ta Li, Hui-Wen Chang, Meng-Hsien Chen, Hue-Ying Chiou, Bang-Yeh Liou, Victor Fei Pang, Wei-Cheng Yang, Chian-Ren Jeng
Silver, such as silver nanoparticles (AgNPs), has been widely used in commercial products and may be released into the environment. The interaction between Ag deposition and biological systems is raising serious concerns because of one health consideration. Cetaceans, as the top predators of the oceans, may be exposed to Ag/Ag compounds and suffer negative health impacts from the deposition of these compounds in their bodies. In the present study, we utilized autometallography (AMG) to localize the Ag in the liver and kidney tissues of cetaceans and developed a model called the cetacean histological Ag assay (CHAA) to estimate the Ag concentrations in the liver and kidney tissues of cetaceans...
January 9, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29325017/cell-type-resolved-alternative-splicing-patterns-in-mouse-liver
#2
Peng Wu, Donghu Zhou, Weiran Lin, Yanyan Li, Handong Wei, Xiaohong Qian, Ying Jiang, Fuchu He
Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcription diversity. However, the functional roles of AS in multiple cell types from one organ have not been reported. Here, we provide the most comprehensive profile for cell-type-resolved AS patterns in mouse liver. A total of 13,637 AS events are detected, representing 81.5% of all known AS events in the database. About 46.2% of multi-exon genes undergo AS from the four cell types of mouse liver: hepatocyte, liver sinusoidal endothelial cell, Kupffer cell and hepatic stellate cell, which regulates cell-specific functions and maintains cell characteristics...
January 8, 2018: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29320626/directing-nanoparticle-biodistribution-through-evasion-and-exploitation-of-stab2-dependent-nanoparticle-uptake
#3
Frederick Campbell, Frank L Bos, Sandro Sieber, Gabriela Arias-Alpizar, Bjørn E Koch, Jörg Huwyler, Alexander Kros, Jeroen Bussmann
Up to 99% of systemically administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells), although significant nanoparticle interactions with other hepatic cells have also been observed. To achieve effective cell-specific targeting of drugs through nanoparticle encapsulation, improved mechanistic understanding of nanoparticle-liver interactions is required. Here, we show the caudal vein of the embryonic zebrafish (Danio rerio) can be used as a model for assessing nanoparticle interactions with mammalian liver sinusoidal (or scavenger) endothelial cells (SECs) and macrophages...
January 10, 2018: ACS Nano
https://www.readbyqxmd.com/read/29318378/mac-2-binding-protein-glycan-isomer-m2bpgi-is-a-new-serum-biomarker-for-assessing-liver-fibrosis-more-than-a-biomarker-of-liver-fibrosis
#4
REVIEW
Ken Shirabe, Yuki Bekki, Dolgormaa Gantumur, Kenichiro Araki, Norihiro Ishii, Atsushi Kuno, Hisashi Narimatsu, Masashi Mizokami
Assessing liver fibrosis is important for predicting the efficacy of antiviral therapy and patient prognosis. Liver biopsy is the gold standard for diagnosing liver fibrosis, despite its invasiveness and problematic diagnostic accuracy. Although noninvasive techniques to assess liver fibrosis are becoming important, reliable serum surrogate markers are not available. A glycoproteomics study aimed at identifying such markers discovered Mac 2-Binding Protein Gylcan Isomer (M2BPGi), which is a reliable marker for assessing liver fibrosis in patients with viral hepatitis and other fibrotic liver diseases such as primary biliary cholangitis, biliary atresia, autoimmune hepatitis, and nonalcoholic fatty liver disease...
January 9, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29317674/spred2-deficiency-exacerbates-d-galactosamine-lipopolysaccharide-induced-acute-liver-injury-in-mice-via-increased-production-of-tnf%C3%AE
#5
Xu Yang, Masayoshi Fujisawa, Teizo Yoshimura, Toshiaki Ohara, Miwa Sato, Megumi Mino, Thar Htet San, Tong Gao, Steven L Kunkel, Akihiro Matsukawa
Acute liver injury (ALI) is characterized by hepatocyte damage and inflammation. In the present study, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences ALI induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). Compared to wild-type mice, Spred2-/- mice developed exacerbated liver injury represented by enhanced hepatocyte damage and inflammation. Enhanced ERK activation was observed in Spred2-/--livers, and the MEK/ERK inhibitor U0126 ameliorated ALI...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316949/ezh2-promotes-hepatocellular-carcinoma-progression-through-modulating-mir-22-galectin-9-axis
#6
Shaofei Chen, Jiarui Pu, Jie Bai, Yuping Yin, Ke Wu, Jiliang Wang, Xiaoming Shuai, Jinbo Gao, Kaixiong Tao, Guobin Wang, Hang Li
BACKGROUND: Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. METHODS: Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ...
January 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29301830/activation-of-4-1bb-on-liver-myeloid-cells-triggers-hepatitis-via-an-interleukin-27-dependent-pathway
#7
Todd Bartkowiak, Ashvin R Jaiswal, Casey R Ager, Renee Chin, Chao-Hsien Chen, Pratha Budhani, Midan Ai, Matthew J Reilley, Manu M Sebastian, David S Hong, Michael A Curran
PURPOSE: Agonist antibodies targeting the T cell co-stimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across pre-clinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist driven tumor immunity from hepatotoxicity. EXPERIMENTAL DESIGN: The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without co-administration of checkpoint blockade, via 1) measurement of serum transaminase levels, 2) imaging of liver immune infiltrates, and 3) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29299986/significance-of-hepatoprotective-liver-specific-targeted-drug-delivery-a-review-on-novel-herbal-and-formulation-approaches-in-management-of-hepatotoxicity
#8
Surbhi Rohilla, D C Bhatt
BACKGROUND: The liver is the largest and vital organ present in all vertebrates. It performs various major functions such as detoxification, metabolism, protein synthesis, excretion and so on. Liver cells are divided into parenchymal cells and non-parenchymal cells. Hepatocytes, Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells, etc are found in liver having different receptors present on their surface which can be used for liver targeting by binding to different ligands...
January 3, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29296203/the-pathogenesis-of-diclofenac-induced-immunoallergic-hepatitis-in-a-canine-model-of-liver-injury
#9
Saravanakumar Selvaraj, Jung-Hwa Oh, Reinhard Spanel, Florian Länger, Hyoung-Yun Han, Eun-Hee Lee, Seokjoo Yoon, Jürgen Borlak
Hypersensitivity to non-steroidal anti-inflammatory drugs is a common adverse drug reaction and may result in serious inflammatory reactions of the liver. To investigate mechanism of immunoallergic hepatitis beagle dogs were given 1 or 3 mg/kg/day (HD) oral diclofenac for 28 days. HD diclofenac treatment caused liver function test abnormalities, reduced haematocrit and haemoglobin but induced reticulocyte, WBC, platelet, neutrophil and eosinophil counts. Histopathology evidenced hepatic steatosis and glycogen depletion, apoptosis, acute lobular hepatitis, granulomas and mastocytosis...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287776/activin-a-causes-hepatic-stellate-cell-activation-via-the-induction-of-tnf%C3%AE-%C3%AE%C2%BA%C3%AE-%C3%AE-tgf%C3%AE-in-kupffer-cells
#10
Foteini Kiagiadaki, Marilena Kampa, Argyro Voumvouraki, Elias Castanas, Elias Kouroumalis, George Notas
Background&Aims. TGFβ superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells., where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased...
December 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29276215/deletion-of-both-p62-and-nrf2-spontaneously-results-in-the-development-of-nonalcoholic-steatohepatitis
#11
Kentaro Akiyama, Eiji Warabi, Kosuke Okada, Toru Yanagawa, Tetsuro Ishii, Katsumi Kose, Katsutoshi Tokushige, Kazunori Ishige, Yuji Mizokami, Kenji Yamagata, Kojiro Onizawa, Shun-Ichi Ariizumi, Masakazu Yamamoto, Junichi Shoda
Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism(s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance...
December 25, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29274730/type-i-interferon-receptor-signaling-delays-kupffer-cell-replenishment-during-acute-fulminant-viral-hepatitis
#12
Katharina Borst, Theresa Frenz, Julia Spanier, Pia-Katharina Tegtmeyer, Chintan Chhatbar, Jennifer Skerra, Luca Ghita, Sukumar Namineni, Stefan Lienenklaus, Mario Köster, Mathias Heikenwaelder, Gerd Sutter, Ulrich Kalinke
BACKGROUND AND AIM: Virus-induced fulminant hepatitis is a major cause of acute liver failure. During acute viral hepatitis the impact of type I interferon (IFN-I) on myeloid cells, including liver-resident Kupffer cells (KC), is only partially understood. Here we dissected the impact of locally induced IFN-I responses on myeloid cell function and hepatocytes during acute liver inflammation. METHODS: Two different DNA-encoded viruses, vaccinia virus (VACV) and murine cytomegalovirus (MCMV), were studied...
December 2, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29251792/extracellular-vesicles-from-mice-with-alcoholic-liver-disease-carry-a-distinct-protein-cargo-and-induce-macrophage-activation-via-hsp90
#13
Banishree Saha, Fatemeh Momen-Heravi, Istvan Furi, Karen Kodys, Donna Catalano, Anwesha Gangopadhyay, Reka Haraszti, Abhishek Satishchandran, Arvin Iracheta-Vellve, Adeyinka Adejumo, Scott A Shaffer, Gyongyi Szabo
A salient feature of alcoholic liver disease (ALD) is Kupffer cell (KC) activation and recruitment of inflammatory monocytes/macrophages (Mo/MØ). These key cellular events of ALD pathogenesis may be mediated by extracellular vesicles (EVs). EVs transfer biomaterials, including proteins and miRNAs, and have recently emerged as important effectors of intercellular communication. We hypothesized that circulating EVs from mice with ALD have a protein cargo characteristic of the disease and mediate biological effects by activating immune cells...
December 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29248968/contradictory-intrahepatic-immune-responses-activated-in-high-load-hepatitis-c-virus-livers-compared-with-low-load-livers
#14
Mariko Ishibashi, Hiromi Yamaguchi, Yukari Hirotani, Akihisa Sakurada, Toshihide Endo, Masahiko Sugitani, Tadatoshi Takayama, Makoto Makishima, Mariko Esumi
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area...
December 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29247122/prostaglandin-i2-suppresses-the-development-of-diet-induced-nonalcoholic-steatohepatitis-in-mice
#15
Shima Kumei, Koh-Ichi Yuhki, Fumiaki Kojima, Hitoshi Kashiwagi, Yoshitaka Imamichi, Toshikatsu Okumura, Shuh Narumiya, Fumitaka Ushikubi
Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. Although the prostaglandin (PG)I2 receptor IP is expressed broadly in the liver, the role of PGI2-IP signaling in the development of NASH remains to be determined. Here, we investigated the role of the PGI2-IP system in the development of steatohepatitis using mice lacking the PGI2 receptor IP [IP-knockout (IP-KO) mice] and beraprost (BPS), a specific IP agonist. IP-KO and wild-type (WT) mice were fed a methionine- and choline-deficient diet (MCDD) for 2, 5, or 10 wk...
December 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29236785/the-soluble-mannose-receptor-smr-is-elevated-in-alcoholic-liver-disease-and-associated-with-disease-severity-portal-hypertension-and-mortality-in-cirrhosis-patients
#16
Thomas Damgaard Sandahl, Sidsel Hyldgaard Støy, Tea Lund Laursen, Sidsel Rødgaard-Hansen, Holger Jon Møller, Søren Møller, Hendrik Vilstrup, Henning Grønbæk
BACKGROUND AND AIMS: Hepatic macrophages (Kupffer cells) are involved in the immunopathology of alcoholic liver disease (ALD). The mannose receptor (MR, CD206), expressed primarily by macrophages, mediates endocytosis, antigen presentation and T-cell activation. A soluble form, sMR, has recently been identified in humans. We aimed to study plasma sMR levels and its correlation with disease severity and survival in ALD patients. METHODS: We included 50 patients with alcoholic hepatitis (AH), 68 alcoholic cirrhosis (AC) patients (Child-Pugh A (23), B (24), C (21)), and 21 healthy controls (HC)...
2017: PloS One
https://www.readbyqxmd.com/read/29235119/v-set-and-ig-domain-containing-4-vsig4-expressing-hepatic-f4-80-cells-regulate-oral-antigen-specific-responses-in-mouse
#17
Wonhwa Shin, Youkyoung Jeon, Inhak Choi, Yeon-Jeong Kim
Oral tolerance can prevent unnecessary immune responses against dietary antigens. Members of the B7 protein family play critical roles in the positive and/or negative regulation of T cell responses to interactions between APCs and T cells. V-set and Ig domain-containing 4 (VSIG4), a B7-related co-signaling molecule, has been known to act as a co-inhibitory ligand and may be critical in establishing immune tolerance. Therefore, we investigated the regulation of VSIG4 signaling in a food allergy and experimental oral tolerance murine models...
December 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29234937/-lysosomal-acid-lipase-deficiency-lal-d-diagnostic-and-therapeutic-options-in-an-underdiagnosed-disease
#18
REVIEW
S Synoracki, S Kathemann, K W Schmid, H Jastrow, H A Baba
BACKGROUND AND CLINICAL SETTING: Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells...
December 12, 2017: Der Pathologe
https://www.readbyqxmd.com/read/29228333/dnaaf1-links-heart-laterality-with-the-aaa-atpase-ruvbl1-and-ciliary-intraflagellar-transport
#19
Verity L Hartill, Glenn van de Hoek, Mitali P Patel, Rosie Little, Christopher M Watson, Ian R Berry, Amelia Shoemark, Dina Abdelmottaleb, Emma Parkes, Chiara Bacchelli, Katarzyna Szymanska, Nine V Knoers, Peter J Scambler, Marius Ueffing, Karsten Boldt, Robert Yates, Paul J Winyard, Beryl Adler, Eduardo Moya, Louise Hattingh, Anil Shenoy, Claire Hogg, Eamonn Sheridan, Ronald Roepman, Dominic Norris, Hannah M Mitchison, Rachel H Giles, Colin A Johnson
DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p...
December 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29227538/abberent-expression-of-nor1-protein-in-tumor-associated-macrophages-contributes-to-the-development-of-den-induced-hepatocellular-carcinoma
#20
Shengnan Chen, Pan Zheng, Wei Wang, Mei Yi, Pan Chen, Jing Cai, Junjun Li, Qian Peng, Yuanyuan Ban, Ying Zhou, Zhaoyang Zeng, Xiaoling Li, Wei Xiong, Guiyuan Li, Bo Xiang
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the sixth most common lethal cancer worldwide. Recent evidences demonstrated that oxidored nitro domain containing protein 1(NOR1), a putative tumor suppressor gene, is overexpressed in human HCC tissues. However, the role of NOR1 in HCC development remains unclear. Here, we described that NOR1 protein level is elevated in HCC and is associated with poorer clinical outcome. However, ecotopic overexpression of NOR1 protein in human HCC cell line HepG2 cells had no effect on cells proliferation, migration and clonality...
December 11, 2017: Journal of Cellular Physiology
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