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https://www.readbyqxmd.com/read/29357190/candidate-biomarkers-for-the-diagnosis-and-prognosis-of-drug-induced-liver-injury-an-international-collaborative-effort
#1
Rachel J Church, Gerd A Kullak-Ublick, Jiri Aubrecht, Herbert L Bonkovsky, Naga Chalasani, Robert J Fontana, Jens C Goepfert, Frances Hackman, Nicholas M P King, Simon Kirby, Patrick Kirby, John Marcinak, Sif Ormarsdottir, Shelli J Schomaker, Ina Schuppe-Koistinen, Francis Wolenski, Nadir Arber, Michael Merz, John-Michael Sauer, Raul J Andrade, Florian van Bömmel, Thierry Poynard, Paul B Watkins
Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2)...
January 22, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29331349/effect-of-a-lect2-on-the-immune-response-of-peritoneal-lecukocytes-against-vibrio-anguillarum-in-roughskin-sculpin
#2
Yingmei Chai, Bailin Cong, Shanshan Yu, Yingying Liu, Xin Man, Lujie Wang, Qian Zhu
Leukocyte cell-derived chemotaxin 2 (LECT2) is a multi-functional protein that is mainly synthesized by the liver. However, its role in roughskin scalping is less known. Here, we cloned a leukocyte cell-derived chemotaxin 2 (TfLECT2) genes in the liver of roughskin scalping, Trachidermus fasciatus, and studied its possible role involved in the immune response against Vibrio anguillarum (V. anguillarum) of peritoneal lecukocytes under in vivo conditions. The cDNA sequence of TfLECT2 is 566 bp in size. Its deduced amino acid (aa) sequence comprises 151 residues, of which the first 16 residues form a putative signal peptide and 101 residues compose a typical peptidase M23 domain in the C-terminal region...
January 10, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29220580/the-influence-of-adiposity-and-acute-exercise-on-circulating-hepatokines-in-normal-weight-and-overweight-obese-men
#3
Jack A Sargeant, Guruprasad P Aithal, Toshinari Takamura, Hirofumi Misu, Hiroaki Takayama, Jessica A Douglas, Mark C Turner, David J Stensel, Myra A Nimmo, David R Webb, Thomas Yates, James A King
Hepatokines are liver-secreted proteins with potential to influence glucose regulation and other metabolic parameters. This study investigated differences in adiposity status on five novel hepatokines and characterised their response to acute moderate-intensity exercise in groups of normal weight and overweight/obese men. Twenty-two men were recruited into normal weight and overweight/obese groups (BMI: 18.5 to 24.9 and 25.0 to 34.9 kg∙m<sup>-2</sup>). Each completed two experimental trials, exercise and control...
December 8, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29090278/alleviation-of-lipopolysaccharide-d-galactosamine-induced-liver-injury-in-leukocyte-cell-derived-chemotaxin-2-deficient-mice
#4
Akinori Okumura, Takeshi Saito, Minoru Tobiume, Yuki Hashimoto, Yuko Sato, Takashi Umeyama, Minoru Nagi, Koichi Tanabe, Hiroyuki Unoki-Kubota, Yasushi Kaburagi, Hideki Hasegawa, Yoshitsugu Miyazaki, Satoshi Yamagoe
Leukocyte cell-derived chemotaxin 2 (LECT2) is a secreted pleiotropic protein that is mainly produced by the liver. We have previously shown that LECT2 plays an important role in the pathogenesis of inflammatory liver diseases. Lipopolysaccharide/d-galactosamine (LPS/d-GalN)-induced acute liver injury is a known animal model of fulminant hepatic failure. Here we found that this hepatic injury was alleviated in LECT2-deficient mice. The levels of TNF-α and IFN-γ, which mediate this hepatitis, had significantly decreased in these mice, with the decrease in IFN-γ production notably greater than that in TNF-α...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29056545/characterization-of-the-lect2-gene-and-its-protective-effects-against-microbial-infection-via-large-lymphocytes-in-lampetra-japonica
#5
Zhiliang Wang, Jiali Lu, Changzhi Li, Qingwei Li, Yue Pang
Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional protein of the innate immune system that defends against bacterial infections and chemotactic activity. However, its precise function in lamprey remains unclear. In this study, a novel LECT2 gene was first cloned from Lampetra japonica. The full-length cDNA sequence of L-LECT2 consists of a 606-bp ORF encoding a protein of 201 amino acid residues. L-LECT2 has greater than 50% sequence identity with its homologs in jawed vertebrates. FACS and immunohistochemistry assays were used to determine that the L-LECT2 protein was primarily distributed in the intestines and supraneural body tissues of lamprey, also marginally detectable in leukocytes...
October 19, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28828707/pathology-and-diagnosis-of-renal-non-al-amyloidosis
#6
REVIEW
Sanjeev Sethi, Jason D Theis
Renal amyloidosis is characterized by acellular Congo red positive deposits in the glomeruli, interstitium and/or arteries. Light chain restriction on immunofluorescence studies is present in AL-amyloidosis, the most common type of amyloidosis involving the kidney. The detection of Congo red positive deposits coupled with negative immunofluorescence studies is highly suggestive of non-AL amyloidosis. Some of the non-AL amyloidosis are common while others are relatively rare. The clinical features, laboratory and renal pathology findings are helpful in the diagnosis and typing of non-AL amyloidosis...
August 21, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28623956/differential-protein-expression-in-chicken-macrophages-and-heterophils-in-vivo-following-infection-with-salmonella-enteritidis
#7
Zuzana Sekelova, Hana Stepanova, Ondrej Polansky, Karolina Varmuzova, Marcela Faldynova, Radek Fedr, Ivan Rychlik, Lenka Vlasatikova
In this study we compared the proteomes of macrophages and heterophils isolated from the spleen 4 days after intravenous infection of chickens with Salmonella Enteritidis. Heterophils were characterized by expression of MMP9, MRP126, LECT2, CATHL1, CATHL2, CATHL3, LYG2, LYZ and RSFR. Macrophages specifically expressed receptor proteins, e.g. MRC1L, LRP1, LGALS1, LRPAP1 and a DMBT1L. Following infection, heterophils decreased ALB and FN1, and released MMP9 to enable their translocation to the site of infection...
June 17, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28584627/mixed-leukocyte-cell-derived-chemotaxin-2-and-amyloid-a-renal-amyloidosis-in-a-kazakh-german-patient
#8
Vega A Gödecke, Christoph Röcken, Lars Steinmüller-Magin, Felix Nadrowitz, Susanne V Fleig, Hermann Haller, Annette D Wagner
Leukocyte cell-derived chemotaxin 2 (LECT2)-related amyloidosis (ALECT2) constitutes a subtype of systemic amyloidosis affecting the kidney. This is the first case describing mixed ALECT2 and Amyloid A renal amyloidosis in a Kazakh-German patient. Genetic analysis shows a polymorphism in the LECT2 gene and a homozygous mutation in the SAA1 gene. Notably, our patient has a body mass index of 61 kg/m(2) and a pathological glucose tolerance test. ALECT2 was found in certain ethnic groups with a high incidence of diabetes...
April 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28476670/functional-diets-modulate-the-acute-phase-protein-response-in-oncorhynchus-mykiss-subjected-to-chronic-stress-and-challenged-with-vibrio-anguillarum
#9
Darlyng Castro-Osses, Crisleri Carrera-Naipil, Cristian Gallardo-Escárate, Ana Teresa Gonçalves
The acute phase response to pathogens alters the production of proinflammatory cytokines that, in turn, activate the synthesis of acute phase proteins. These proteins neutralize, prevent, and indicate tissue damage, thereby influencing the specific immune response and allowing the organism to regain homeostasis. Functional diets based in pre- and probiotics are used in aquaculture to improve fish health and resistance to diseases, but there is an information gap on the mechanisms involved in these effects and if these diets are efficient when fish are raised under high stocking densities...
May 2, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28376109/association-of-leukocyte-cell-derived-chemotaxin-2-lect2-with-nafld-metabolic-syndrome-and-atherosclerosis
#10
Hye Jin Yoo, Soon Young Hwang, Ju-Hee Choi, Hyun Jung Lee, Hye Soo Chung, Ji-A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi, Kyung Mook Choi
OBJECTIVE: Previous studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a recently discovered hepatokine, is associated with the inflammatory response and insulin resistance. We examined circulating plasma LECT2 levels in the subjects with non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome. METHODS: We analyzed plasma LECT2 levels from the subjects of age- and sex-matched 320 adults with or without NAFLD who completed a health check-up at the Health Promotion Center of Korea University Guro Hospital...
2017: PloS One
https://www.readbyqxmd.com/read/28278265/visceral-fat-area-is-a-strong-predictor-of-leukocyte-cell-derived-chemotaxin-2-a-potential-biomarker-of-dyslipidemia
#11
Kumpei Tanisawa, Hirokazu Taniguchi, Xiaomin Sun, Tomoko Ito, Ryoko Kawakami, Shizuo Sakamoto, Mitsuru Higuchi
BACKGROUND: Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human...
2017: PloS One
https://www.readbyqxmd.com/read/27983994/reduced-serum-level-of-leukocyte-cell-derived-chemotaxin-2-is-associated-with-the-presence-of-diabetic-retinopathy
#12
Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR...
October 28, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-coexpression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#13
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently, we have shown that coexpression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to hepatocellular carcinoma (HCC) in mice that corresponds to around 10% of human HCC. In the current study, we investigate whether Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in an HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
May 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27816666/reduced-serum-level-of-leukocyte-cell-derived-chemotaxin-2-is-associated-with-the-presence-of-diabetic-retinopathy
#14
Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR...
December 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27813598/lect2-association-with-macrophage-mediated-killing-of-helicobacter-pylori-by-activating-nf-%C3%AE%C2%BAb-and-nitric-oxide-production
#15
H X Shen, L Li, Q Chen, Y Q He, C H Yu, C Q Chu, X J Lu, J Chen
Helicobacter pylori employs unique methods to colonize the stomach, which induces chronic inflammation. It is also able to avoid eradication by macrophages and other immune cells. Leukocyte cell-derived chemotaxin 2 (LECT2), a multi-functional cytokine involved in many pathological conditions, has recently been shown to activate macrophages via the CD209a receptor. Therefore, we aimed to investigate the effects of LECT2 on H. pylori-infected macrophages. Macrophages were treated with recombinant LECT2, and both their ability to kill H...
October 24, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27705746/a-multi-protein-receptor-ligand-complex-underlies-combinatorial-dendrite-guidance-choices-in-c-elegans
#16
Wei Zou, Ao Shen, Xintong Dong, Madina Tugizova, Yang K Xiang, Kang Shen
Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells...
October 5, 2016: ELife
https://www.readbyqxmd.com/read/27596364/lect2-drives-haematopoietic-stem-cell-expansion-and-mobilization-via-regulating-the-macrophages-and-osteolineage-cells
#17
Xin-Jiang Lu, Qiang Chen, Ye-Jing Rong, Guan-Jun Yang, Chang-Hong Li, Ning-Yi Xu, Chao-Hui Yu, Hui-Ying Wang, Shun Zhang, Yu-Hong Shi, Jiong Chen
Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells...
2016: Nature Communications
https://www.readbyqxmd.com/read/27562717/rapid-response-of-the-steatosis-sensing-hepatokine-lect2-during-diet-induced-weight-cycling-in-mice
#18
Keita Chikamoto, Hirofumi Misu, Hiroaki Takayama, Akihiro Kikuchi, Kiyo-Aki Ishii, Fei Lan, Noboru Takata, Natsumi Tajima-Shirasaki, Yumie Takeshita, Hirohiko Tsugane, Shuichi Kaneko, Seiichi Matsugo, Toshinari Takamura
Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days...
September 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27507763/inhibition-of-vegf165-vegfr2-dependent-signaling-by-lect2-suppresses-hepatocellular-carcinoma-angiogenesis
#19
Chi-Kuan Chen, Wen-Hsuan Yu, Tsu-Yao Cheng, Min-Wei Chen, Chia-Yi Su, Yi-Chieh Yang, Tsang-Chih Kuo, Ming-Tsan Lin, Ya-Chi Huang, Michael Hsiao, Kuo-Tai Hua, Mien-Chie Hung, Min-Liang Kuo
Hepatocellular carcinoma (HCC) relies on angiogenesis for growth and metastasis. Leukocyte cell-derived chemotaxin 2 (LECT2) is a cytokine and preferentially expressed in the liver. Previous studies have found that LECT2 targets to both immune and tumor cells to suppress HCC development and vascular invasion. Although LECT2 did not affect HCC cells growth in vitro, it still suppressed HCC xenografts growth in immune-deficient mice, suggesting other cells such as stroma cells may also be targeted by LECT2. Here, we sought to determine the role of LECT2 in tumor angiogenesis in HCC patients...
August 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27451901/muscle-and-skin-derived-cues-jointly-orchestrate-patterning-of-somatosensory-dendrites
#20
Carlos A Díaz-Balzac, Maisha Rahman, María I Lázaro-Peña, Lourdes A Martin Hernandez, Yehuda Salzberg, Cristina Aguirre-Chen, Zaven Kaprielian, Hannes E Bülow
Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1-3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin-SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the leucine-rich transmembrane receptor DMA-1/LRR-TM expressed on PVD neurons [8, 9]...
September 12, 2016: Current Biology: CB
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