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https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#1
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737156/thyroid-function-of-steatitis-affected-mozambique-tilapia-oreochromis-mossambicus-from-a-sub-tropical-african-reservoir
#2
J Dabrowski, P Oberholster, J Steyl, G Osthoff, A Hugo, D M Power, J H van Wyk
Thyroid function and nutritional indicators were measured in obese, steatitis-affected Mozambique tilapia Oreochromis mossambicus from Loskop Reservoir (LR), South Africa. Plasma thyroid hormones (especially T3) and thyroid follicle histomorphology revealed high levels of activity in every aspect of the thyroid cascade measured in fish from LR compared to a reference population of steatitis-free fish. Concurrent measurements of nutritional state including plasma lipids, liver lipid content and hepatocyte size showed that fish from LR had significant energy stores indicative of abundant nutritional intake...
July 24, 2017: Diseases of Aquatic Organisms
https://www.readbyqxmd.com/read/28736524/immune-and-metabolic-regulation-mechanism-of-dangguiliuhuang-decoction-against-insulin-resistance-and-hepatic-steatosis
#3
Hui Cao, Lingling Tuo, Yali Tuo, Ziyun Xia, Rong Fu, Yang Liu, Yihong Quan, Jue Liu, Zhihong Yu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) is a traditional Chinese medicine (TCM) formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28735525/oxygen-tension-independent-protection-against-hypoxic-cell-killing-in-rat-liver-by-low-sodium
#4
Andrea Ferrigno, Laura G Di Pasqua, Clarissa Berardo, Veronica Siciliano, Plinio Richelmi, Mariapia Vairetti
The role of Na+ in hypoxic injury was evaluated by a time-course analysis of damage in isolated livers perfused with N2-saturated buffer containing standard (143 mM) or low (25 mM) Na+ levels. Trypan blue uptake was used to detect non-viable cells. Under hypoxia with standard-Na+, trypan blue uptake began at the border between pericentral areas and periportal regions and increased in the latter zone; using a low-Na+ buffer, no trypan blue zonation occurred but a homogenous distribution of dye was found associated with sinusoidal endothelial cell (SEC) staining...
May 30, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28735385/preparation-of-decellularized-liver-scaffolds-and-recellularized-liver-grafts
#5
Yibin Chen, Sharon Geerts, Maria Jaramillo, Basak E Uygun
Severe liver disease is the 12th leading cause of death in the USA, with organ transplantation often being the only viable option for treatment. However, due to the shortage of viable donor livers, it is estimated that over 1200 patients died in 2015 while waiting for liver transplantation. This highlights the need for alternative sources of viable organs. In this study, we describe a method that provides the groundwork for the development of functional liver grafts. The approach described here is for removal of cells from intact livers and subsequently repopulating them with functional liver cells...
July 23, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735098/cholangiocytes-cell-transplantation
#6
REVIEW
Lorenzo Ridola, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Due to significant limitations to the access to orthotropic liver transplantation, cell therapies for liver diseases have gained large interest worldwide. SCOPE OF REVIEW: To revise current literature dealing with cell therapy for liver diseases. We discussed the advantages and pitfalls of the different cell sources tested so far in clinical trials and the rationale underlying the potential benefits of transplantation of human biliary tree stem cells (hBTSCs)...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733541/a-validated-transitional-and-translational-porcine-model-of-hepatocellular-carcinoma
#7
Kyle M Schachtschneider, Regina M Schwind, Kwame A Darfour-Oduro, Arun K De, Lauretta A Rund, Kuldeep Singh, Daniel R Principe, Grace Guzman, Charles E Ray, Howard Ozer, Ron C Gaba, Lawrence B Schook
Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733363/lipidomic-profiling-of-patient-specific-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells
#8
Mostafa Kiamehr, Leena E Viiri, Terhi Vihervaara, Kaisa M Koistinen, Mika Hilvo, Kim Ekroos, Reijo Käkelä, Katriina Aalto-Setälä
Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model for primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a 3-step protocol through definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid metabolism-related genes were performed during the entire differentiation process from iPSC to HLCs...
July 21, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28733206/omics-based-identification-of-the-combined-effects-of-idiosyncratic-drugs-and-inflammatory-cytokines-on-the-development-of-drug-induced-liver-injury
#9
J Jiang, K Mathijs, L Timmermans, S M Claessen, A Hecka, J Weusten, R Peters, J H van Delft, J C S Kleinjans, D G J Jennen, T M de Kok
The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis...
July 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28732575/beraprost-sodium-a-prostacyclin-analogue-reduces-fructose-induced-hepatocellular-steatosis-in-mice-and-in-vitro-via-the-microrna-200a-and-sirt1-signaling-pathway
#10
Pengyuan Zhang, Lijuan Xu, Hongyu Guan, Liehua Liu, Juan Liu, Zhimin Huang, Xiaopei Cao, Zhihong Liao, Haipeng Xiao, Yanbing Li
PURPOSE: To determine whether beraprost sodium, a prostacyclin analogue, could reduce hepatic lipid accumulation induced by fructose in mice and cultured human hepatocytes, and to investigate the expression of microRNAs and the sirtuin 1 (SIRT1) pathway. METHODS: Male C57BL/6JNju mice were divided into three groups and fed one of the following diets: a normal diet, a high fructose diet, or a high fructose diet with beraprost sodium treatment. In addition, human-derived HepG2 cells were cultured and treated with fructose (25mmol/L) with or without beraprost sodium (10μmol/L) for 24h, and transfected with small interfering RNA (siRNA) against SIRT1, miR-200a mimic, or miR-200a inhibitor for 48h...
August 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28731143/suppression-of-hepatic-dysfunction-in-tenascin%C3%A2-x%C3%A2-deficient-mice-fed-a-high%C3%A2-fat-diet
#11
Shinsaku Yamaguchi, Kohei Kawakami, Kazumi Satoh, Naoki Fukunaga, Kazuhito Akama, Ken-Ichi Matsumoto
Extracellular matrix glycoprotein tenascin‑X (TNX) is the largest member of the tenascin family. In the present study, the contribution of TNX to liver dysfunction was investigated by administration of high‑fat and high‑cholesterol diet with high levels of phosphorus and calcium (HFCD) to wild‑type (WT) and TNX‑knockout (KO) mice. After 16 weeks of HFCD administration, the ratio of liver weight to body weight was approximately 22% higher in the HFCD‑fed WT mice compared with the HFCD‑fed TNX‑KO mice, indicating hepatomegaly in HFCD‑fed WT mice...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730878/investigational-drugs-in-development-for-hepatitis-d
#12
Mario Rizzetto
Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis ...
July 21, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28730856/in-vitro-drug-drug-interactions-of-budesonide-inhibition-and-induction-of-transporters-and-cytochrome-p450-enzymes
#13
Nancy Chen, Donghui Cui, Qing Wang, Zhiming Wen, Richard D Finkelman, Devin Welty
1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28730823/pathophysiological-analysis-of-the-progression-of-hepatic-lesions-in-stam-mice
#14
T Saito, M Muramatsu, Y Ishii, Y Saigo, T Konuma, Y Toriniwa, K Miyajima, T Ohta
Nonalcoholic steatohepatitis (NASH) is a current health issue since the disease often leads to hepatocellular carcinoma; however, the pathogenesis of the disease has still not been fully elucidated. In this study, we investigated the pathophysiological changes observed in hepatic lesions in STAM mice, a novel NASH model. STAM mice, high fat-diet (HFD) fed mice, and streptozotocin (STZ) treated mice were prepared, and changes over time, such as biological parameters, mRNA expression, and histopathological findings, were evaluated once animal reached 5, 7, and 10 weeks of age...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28729907/current-status-of-pediatric-transplantation-in-japan
#15
REVIEW
Nao Nishimura, Mureo Kasahara, Kenji Ishikura, Satoshi Nakagawa
Brain-dead donor organ transplantation has been available to children in Japan since the 2010 revision of the Organ Transplant Law. Of the 50-60 brain-dead donor organ transplants performed annually in Japan, however, very few (0-4 per year) are performed in children. Again, while those receiving liver, heart, and kidney transplants are reported to fare better than their counterparts in the rest of the world, organ shortage is becoming a matter of great concern. Very few organs become available from brain-dead donors or are transplanted to adults if made available at all, with some children dying while on the brain-dead organ waiting list...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28729838/detection-of-emodin-derived-glutathione-adduct-in-normal-rats-administered-with-large-dosage-of-polygoni-multiflori-radix
#16
Li-Long Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. PMR-associated hepatotoxicity has been drawing increasingly more attention in recent years in parallel with its wide utilization. Anthraquinones (AQs) are recognized as the main hepatotoxic components in PMR. However, the exact underlying mechanism of AQs poisoning is still not fully understood. Herein, we proposed a hypothesis that metabolic activation of AQs such as emodin was involved in PMR-induced liver injury, AQs followed to generate the electrophilic reactive metabolites and subsequently formed covalent adduct with cellular nucleophiles in the liver to exert hepatotoxicity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28729654/cryopreservation-protocol-for-human-biliary-tree-stem-progenitors-hepatic-and-pancreatic-precursors
#17
Lorenzo Nevi, Vincenzo Cardinale, Guido Carpino, Daniele Costantini, Sabina Di Matteo, Alfredo Cantafora, Fabio Melandro, Roberto Brunelli, Carlo Bastianelli, Camilla Aliberti, Marco Monti, Daniela Bosco, Pasquale Bartolomeo Berloco, Pierluigi Benedetti Panici, Lola Reid, Eugenio Gaudio, Domenico Alvaro
Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729463/dietary-pufas-attenuate-nlrp3-inflammasome-activation-via-enhancing-macrophage-autophagy
#18
Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how NLRP3 inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice...
July 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28729435/dysregulation-of-mir-223-constitutes-a-promising-biomarker-that-informs-about-clinical-outcomes-of-acute-liver-failure
#19
Volker M Lauschke
In this issue of Clinical Science, Schueller et al. [Clin. Sci. (2017) 131, 1971-1987] evaluated the role of miR-223 across multiple etiologies of acute and chronic liver insults in murine models and clinical samples. The authors find that while miR-223 is not mechanistically involved in liver injury, its intracellular levels in hepatocytes are increased upon hepatic damage in a broad panel of mechanistically distinct injury models. Furthermore, the authors provide evidence that circulating miR-223 levels provide a promising minimally invasive biomarker for acute liver failure (ALF) that defines a distinct subset of ALF cases and correlates with clinical outcomes...
August 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28728456/quillaja-saponaria-bark-saponin-protects-wistar-rats-against-ferrous-sulphate-induced-oxidative-and-inflammatory-liver-damage
#20
Mustafa Ahmed Abdel-Reheim, Basim Anwar Shehata Messiha, Ali Ahmed Abo-Saif
CONTEXT: Saponins from different sources are historically reported in Chinese medicine to possess many beneficial effects. However, insufficient experimental data are available regarding the hepatoprotective potential of Quillaja bark saponin. OBJECTIVE: The protective effect of Quillaja saponaria Molina (Quillajaceae) bark triterpenoid saponin against iron-induced hepatotoxicity is compared to the standard N-acetylcysteine in adult male Wistar rats. MATERIALS AND METHODS: Animals were divided into (six) groups, namely a normal control, an N-acetylcysteine control (300 mg/kg/day, p...
December 2017: Pharmaceutical Biology
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