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Liver regeneration

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https://www.readbyqxmd.com/read/28637104/-treatment-options-in-non-alcoholic-fatty-liver-disease
#1
REVIEW
Won Kim
The prevalence of non-alcoholic fatty liver disease (NAFLD) has sharply increased over the past several decades in Korea. In most cases of NAFLD, metabolic stress and cellular apoptosis are often driven by metabolic abnormality, eventually leading to inflammation and fibrosis . Along with a dramatic surge in the obesity epidemic, 10-20% of NAFLD patients ultimately progress to non-alcoholic steatohepatitis (NASH), a precursor to cirrhosis and hepatocellular carcinoma, as well as multi-organ systemic diseases...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28636371/iron-oxidation-and-core-formation-in-recombinant-heteropolymeric-human-ferritins
#2
Matthew R Mehlenbacher, Maura Poli, Paolo Arosio, Paolo Santambrogio, Sonia Levi, N Dennis Chasteen, Fadi Bou-Abdallah
In animals, the iron storage and detoxification protein, ferritin, is composed of two functionally and genetically distinct subunit types, H (Heavy) and L (Light), which co-assemble in various ratios with tissue specific distributions to form shell-like protein structures of 24 subunits within which a mineralized iron core is stored. The H-subunit possesses a ferroxidase center (FC) which catalyzes Fe(II) oxidation whereas the L-subunit does not. To assess the role of the L-subunit in iron oxidation and core formation, two human recombinant heteropolymeric ferritins, designated H-rich and L-rich with ratios of ~ 20H:4L and ~ 22L:2H, respectively, were employed and compared to the human homopolymeric H-subunit ferritin (HuHF)...
June 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28635176/genetic-loss-of-the-muscarinic-m3-receptor-m3-r-markedly-alters-bile-formation-and-cholestatic-liver-injury-in-mice
#3
Franziska Durchschein, Elisabeth Krones, Marion J Pollheimer, Gernot Zollner, Martin Wagner, Jean-Pierre Raufman, Peter Fickert
Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. We compared bile flow and composition in M3 -R knock-out mice (M3 -R(-/-) ) and wild type littermates (WT). M3 -R(-/-) mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3(-) secretion...
June 21, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28631253/portal-branch-ligation-does-not-counteract-the-inhibiting-effect-of-temsirolimus-on-extrahepatic-colorectal-metastatic-growth
#4
Sebastian Senger, Jens Sperling, Barbara Oberkircher, Martin K Schilling, Otto Kollmar, Michael D Menger, Christian Ziemann
The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice...
June 19, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28629077/effects-of-the-surface-modification-of-polyurethane-substrates-on-genotoxicity-and-blood-activation-processes
#5
Roman Major, Hanna Plutecka, Anna Gruszczynska, Juergen M Lackner, Boguslaw Major
The aim of this study was to determine the mutagenic and thrombogenic potential of a material composed of a thin coating deposited on a polymeric substrate. In this work, a surface was modified in a manner that would mimic the function of cellular niches. Finally, the surfaces should actively capture and differentiate progenitor cells from the blood stream. Thin films with 10 to 500nm thicknesses were deposited by unbalanced, pulsed DC magnetron sputtering on smooth polyurethane. Such high energy conditions led to a stiffening of the polymer surface layers by pseudodiffusion during the initial stages of film growth...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28625139/targeting-cholinergic-system-to-modulate-liver-injury
#6
Ravirajsinh N Jadeja, Vikrant P Rachakonda, Sandeep Khurana
Over the past few decades, evidence accumulated to indicate that parasympathetic innervation regulates liver injury and regeneration. Liver derives its parasympathetic input via vagus nerve. In animal models, vagus nerve stimulation and transection are frequently used to determine the impact of parasympathetic input on liver injury responses. Such strategies provide limited understanding of post-neuronal mechanisms involved in regulation of liver injury. The hepatic branch of vagus nerve releases acetylcholine (ACh), which activates muscarinic and nicotinic receptors in hepatocytes as well as non-parenchymal cells to modulate cellular functions...
June 18, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28624210/low-dose-gene-therapy-for-murine-pku-using-episomal-naked-dna-vectors-expressing-pah-from-its-endogenous-liver-promoter
#7
Hiu Man Grisch-Chan, Andrea Schlegel, Tanja Scherer, Gabriella Allegri, Raphael Heidelberger, Panagiota Tsikrika, Marco Schmeer, Martin Schleef, Cary O Harding, Johannes Häberle, Beat Thöny
Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620747/amniotic-fluid-cells-current-progress-and-emerging-challenges-in-renal-regeneration
#8
REVIEW
Stefano Da Sacco, Laura Perin, Sargis Sedrakyan
Amniotic fluid (AF) contains a heterogeneous population of cells that have been identified to possess pluripotent and progenitor-like characteristics. These cells have been applied in various regenerative medicine applications ranging from in vitro cell differentiation to tissue engineering to cellular therapies for different organs including the heart, the liver, the lung, and the kidneys. In this review, we examine the different methodologies used for the derivation of amniotic fluid stem cells and renal progenitors, and their application in renal repair and regeneration...
June 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28620644/topical-application-of-mesenchymal-stromal-cells-ameliorated-liver-parenchyma-damage-after-ischemia-reperfusion-injury-in-an-animal-model
#9
Ping Kuen Lam, Charing Ching Ning Chong, Anthony Wing Ip Lo, Anthony Wing Hung Chan, Cindy See Wai Tong, Don Wai Ching Chin, Kenneth Hoi Kin Wong, Richard Kwong Wai Choy, Andrew Kai-Yip Fung, Yi Xiang Wang, Ka Fai To, Paul Bo San Lai
BACKGROUND: Ischemia-reperfusion injury (IRI) is commonly encountered after liver surgery. This study evaluated the hepatoprotective effects of topically applied adipose-derived mesenchymal stromal cells (ADMSCs) on hepatic IRI in a rat model. METHODS: ADMSCs from transgenic green fluorescent protein Sprague-Dawley rats were topically applied to the liver surface of Sprague-Dawley rats after hepatic IRI and fixed in position by fibrin glue (group A, n = 24). An equivalent amount of ADMSCs were administered through the portal (group B, n = 24) or tail vein (group C, n = 24)...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620383/ly6c-hi-monocytes-and-their-macrophage-descendants-regulate-neutrophil-function-and-clearance-in-acetaminophen-induced-liver-injury
#10
Nadine Graubardt, Milena Vugman, Odelia Mouhadeb, Gabriele Caliari, Metsada Pasmanik-Chor, Debby Reuveni, Ehud Zigmond, Eli Brazowski, Eyal David, Lousie Chappell-Maor, Steffen Jung, Chen Varol
Monocyte-derived macrophages (MoMF) play a pivotal role in the resolution of acetaminophen-induced liver injury (AILI). Timely termination of neutrophil activity and their clearance are essential for liver regeneration following injury. Here, we show that infiltrating Ly6C(hi) monocytes, their macrophage descendants, and neutrophils spatially and temporally overlap in the centrilobular necrotic areas during the necroinflammatory and resolution phases of AILI. At the necroinflammatory phase, inducible ablation of circulating Ly6C(hi) monocytes resulted in reduced numbers and fractions of reactive oxygen species (ROS)-producing neutrophils...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620221/mesenchymal-stem-cell-derived-exosomes-as-a-new-therapeutic-strategy-for-liver-diseases
#11
REVIEW
Guohua Lou, Zhi Chen, Min Zheng, Yanning Liu
The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs...
June 16, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28616151/therapeutic-potential-of-dental-stem-cells
#12
REVIEW
Elna Paul Chalisserry, Seung Yun Nam, Sang Hyug Park, Sukumaran Anil
Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#13
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28612126/immaturity-of-bile-canalicular-ductule-networks-in-the-future-liver-remnant-while-associating-liver-partition-and-portal-vein-occlusion-for-staged-hepatectomy-alpps
#14
Kenichi Matsuo, Yukihiko Hiroshima, Kazuto Yamazaki, Kohei Kasahara, Yutaro Kikuchi, Daisuke Kawaguchi, Takashi Murakami, Yasuo Ishida, Kuniya Tanaka
BACKGROUND: We studied histologic changes of bile canalicular-ductule networks in the future liver remnant (FLR) while associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS), since little is known about regeneration of these networks during the relatively short interval between procedures in ALPPS. METHODS: Bile canalicular-ductule networks were examined in specimens from eight patients treated with ALPPS and six patients undergoing hepatectomy following portal vein embolization (PVE)...
June 13, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28606603/identification-of-enzymes-responsible-for-nitrazepam-metabolism-and-toxicity-in-human
#15
Keigo Konishi, Tatsuki Fukami, Saki Gotoh, Miki Nakajima
Nitrazepam (NZP) is a hypnotic agent that rarely causes liver injuries in humans and teratogenicity in rodents. In humans, NZP is primarily metabolized to 7-aminonitrazepam (ANZP) by reduction and subsequently to 7-acetylamino nitrazepam (AANZP) by acetylation. ANZP can be regenerated from AANZP by hydrolysis in rodents, but it is still unclear whether this reaction occurs in humans. In rodents, AANZP may be associated with teratogenicity, while in humans, it is known that drug-induced liver injuries may be caused by NZP reactive metabolite(s)...
June 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28602644/increased-kinetic-growth-rate-during-late-phase-liver-regeneration-impacts-the-risk-of-tumor-recurrence-after-colorectal-liver-metastases-resection
#16
Georgios A Margonis, Kazunari Sasaki, Nikolaos Andreatos, Manijeh Zargham Pour, Nannan Shao, Mounes Aliyari Ghasebeh, Stefan Buettner, Efstathios Antoniou, Christopher L Wolfgang, Matthew Weiss, Ihab R Kamel, Timothy M Pawlik
BACKGROUND: Although experimental data strongly support the pro-tumorigenic role of postoperative liver regeneration, this hypothesis has not been clinically investigated. We aimed to examine the impact of liver regeneration determined by volumetric imaging on recurrence following resection of colorectal liver metastasis (CRLM). METHODS: Resected liver volume was subtracted from total liver volume (TLV) to define postoperative remnant liver volume (RLVp). Early and late kinetic growth rates (KGR) were defined as the postoperative increases in liver volume within 2-3 and 8-10 months from surgery, respectively, divided by the corresponding time interval...
June 8, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28599872/hepatotoxicity-following-systemic-therapy-for-colorectal-liver-metastases-and-the-impact-of-chemotherapy-associated-liver-injury-on-outcomes-after-curative-liver-resection
#17
REVIEW
G Duwe, S Knitter, S Pesthy, A S Beierle, M Bahra, M Schmelzle, R B Schmuck, P Lohneis, N Raschzok, R Öllinger, M Sinn, B Struecker, I M Sauer, J Pratschke, A Andreou
Patients with colorectal liver metastases (CLM) have remarkably benefited from the advances in medical multimodal treatment and surgical techniques over the last two decades leading to significant improvements in long-term survival. More patients are currently undergoing liver resection following neoadjuvant chemotherapy, which has been increasingly established within the framework of curative-indented treatment strategies. However, the use of several cytotoxic agents has been linked to specific liver injuries that not only impair the ability of liver tissue to regenerate but also decrease long-term survival...
May 18, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28599486/knockout-of-kr%C3%A3-ppel-like-factor-10-suppresses-hepatic-cell-proliferation-in-a-partially-hepatectomized-mouse-model
#18
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599080/bmp-signaling-governs-biliary-driven-liver-regeneration-in-zebrafish-via-tbx2b-and-id2a
#19
Tae-Young Choi, Mehwish Khaliq, Shinya Tsurusaki, Nikolay Ninov, Didier Y R Stainier, Minoru Tanaka, Donghun Shin
Upon mild liver injury, new hepatocytes originate from pre-existing hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast-like cells (HB-LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration...
June 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28597071/the-novel-tool-of-cell-reprogramming-for-applications-in-molecular-medicine
#20
REVIEW
Moritz Mall, Marius Wernig
Recent discoveries in the field of stem cell biology have enabled scientists to "reprogram" cells from one type to another. For example, it is now possible to place adult skin or blood cells in a dish and convert them into neurons, liver, or heart cells. It is also possible to literally "rejuvenate" adult cells by reprogramming them into embryonic-like stem cells, which in turn can be differentiated into every tissue and cell type of the human body. Our ability to reprogram cell types has four main implications for medicine: (1) scientists can now take skin or blood cells from patients and convert them to other cells to study disease processes...
June 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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