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https://www.readbyqxmd.com/read/29785833/species-differences-in-bile-acids-i-plasma-and-urine-bile-acid-composition
#1
Rhishikesh Thakare, Jawaher Abdullah Alamoudi, Nagsen Gautam, A David Rodrigues, Yazen Alnouti
Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee...
May 21, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29763372/acetyl-coa-from-inflammation-induced-fatty-acids-oxidation-promotes-hepatic-malate-aspartate-shuttle-activity-and-glycolysis
#2
Tongxin Wang, Weilei Yao, Ji Li, Qiongyu He, Yafei Shao, Feiruo Huang
Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29750148/expression-and-regulation-profile-of-mature-microrna-in-the-pig-relevance-to-xenotransplantation
#3
REVIEW
Zongpei Song, David K C Cooper, Zhiming Cai, Lisha Mou
The pig is an important source of meat production and provides a valuable model for certain human diseases. MicroRNA (miRNA), which is noncoding RNA and regulates gene expression at the posttranscriptional level, plays a critical role in various biological processes. Studies on identification and function of mature miRNAs in multiple pig tissues are increasing, yet the literature is limited. Therefore, we reviewed current research to determine the miRNAs expressed in specific pig tissues that are involved in carcass values (including muscle and adipocytes), reproduction (including pituitary, testis, and ovary), and development of some solid organs (e...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29748197/minimally-invasive-delivery-of-hydrogel-encapsulated-amiodarone-to-the-epicardium-reduces-atrial-fibrillation
#4
Jose R Garcia, Peter F Campbell, Gautam Kumar, Jonathan J Langberg, Liliana Cesar, Juline N Deppen, Eric Y Shin, Neal K Bhatia, Lanfang Wang, Kai Xu, Frank Schneider, Brian Robinson, Andrés J García, Rebecca D Levit
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although treatment options for AF exist, many patients cannot be maintained in normal sinus rhythm. Amiodarone is an effective medication for AF but has limited clinical utility because of off-target tissue toxicity. METHODS: Here, we use a pig model of AF to test the efficacy of an amiodarone-containing polyethylene glycol-based hydrogel. The gel is placed directly on the atrial epicardium through the pericardial space in a minimally invasive procedure using a specially designed catheter...
May 2018: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/29741632/effects-of-guanidinoacetic-acid-on-growth-performance-creatine-and-energy-metabolism-and-carcass-characteristics-in-growing-finishing-pigs
#5
D T He, X R Gai, L B Yang, J T Li, W Q Lai, X L Sun, L Y Zhang
The aim of this study was to investigate the effects of dietary supplementation with guanidinoacetic acid (GAA) on the growth performance, creatine and energy metabolism, and carcass characteristics in growing-finishing pigs. In Exp. 1, Duroc × Landrace × Yorkshire pigs (n = 180, 33.61 ± 3.91 kg average BW) were blocked by weight and sex, and allotted to five treatments with six replicates (3 gilts and 3 barrows per replicate pen). Diets were corn-soybean meal basal diets supplemented with 0, 300, 600, 900, and 1,200 mg/kg of GAA and fed to the pigs for 98 d...
May 7, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29736835/value-of-two-dimensional-shear-wave-elastography-for-assessing-acute-liver-congestion-in-a-bama-mini-pig-model
#6
Li-Ting Xie, Dan-Xia Xu, Guo Tian, Li-Yun Zhong, Qi-Yu Zhao, Qing-Hong Ke, Tian-An Jiang
BACKGROUND: To date, liver congestion is one of the most significant clinical diseases. However, few studies have profoundly investigated the development, pathology, and prognosis of the important problems associated with acute hepatic congestion. AIMS: To explore the value of noninvasive two-dimensional shear wave elastography (2D-SWE) for assessing acute liver congestion in an animal model. METHODS: Six healthy Bama mini-pigs were used for this research and randomly divided into the experimental group and control group...
May 8, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29723978/ergot-alkaloids-at-doses-close-to-eu-regulatory-limits-induce-alterations-of-the-liver-and-intestine
#7
Viviane Mayumi Maruo, Ana Paula Bracarense, Jean-Paul Metayer, Maria Vilarino, Isabelle P Oswald, Philippe Pinton
An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the intestine using the pig both as a target species and as a non-rodent model for human. Three groups of 24 weaned piglets were exposed for 28 days to control feed or feed contaminated with 1.2 or 2.5 g of sclerotia/kg, i...
May 1, 2018: Toxins
https://www.readbyqxmd.com/read/29698745/evolution-regulation-and-function-of-porcine-selenogenome
#8
REVIEW
Xiao-Dong Chen, Ze-Ping Zhao, Ji-Chang Zhou, Xin Gen Lei
Much less research on regulation and function of selenoproteins has been conducted in domestic pigs than in rodents or humans, although pigs are an excellent model of human nutrition and medicine and pork is a widely consumed meat in the world. Phylogenetically, the 25 identified porcine selenoproteins fell into two primitive groups, and might be further divided into three parallel branches. Despite a high similarity to that of humans and rodents, the porcine selenoproteome exhibited the closest evolutionary relationship with that of sheep and cattle among eight domestic species...
April 23, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29678421/growth-hormone-receptor-deficient-pigs-resemble-the-pathophysiology-of-human-laron-syndrome-and-reveal-altered-activation-of-signaling-cascades-in-the-liver
#9
Arne Hinrichs, Barbara Kessler, Mayuko Kurome, Andreas Blutke, Elisabeth Kemter, Maren Bernau, Armin M Scholz, Birgit Rathkolb, Simone Renner, Sebastian Bultmann, Heinrich Leonhardt, Martin Hrabĕ de Angelis, Hiroshi Nagashima, Andreas Hoeflich, Werner F Blum, Martin Bidlingmaier, Rüdiger Wanke, Maik Dahlhoff, Eckhard Wolf
OBJECTIVE: Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. METHODS: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs...
March 15, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29616108/liver-regeneration-during-the-associating-liver-partition-and-portal-vein-ligation-for-staged-hepatectomy-procedure-in-sus-scrofa-is-positively-modulated-by-stem-cells
#10
Martin Bartas, Jiri Červeň, Jan Oppelt, Matus Peteja, Petr Vávra, Pavel Zonča, Vaclav Procházka, Vaclav Brázda, Petr Pečinka
This present study investigated the impact of the application of stem cells to liver regeneration following the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The experiment was conducted on a pig model (n=6, 3 that did not receive application of stem cells, 3 that received application stem cells). Collected samples of liver (day 0 and 9 following surgery) were subjected to complete transcriptome sequencing. In total, 39 differentially expressed genes were found in the group without the application of the stem cells (genes of unwanted processes such as fibrosis and inflammation)...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29567935/normothermic-machine-perfusion-versus-cold-storage-of-liver-in-pig-model-a-meta-analysis
#11
Shiqi Bian, Zhijun Zhu, Liying Sun, Lin Wei, Wei Qu, Zhigui Zeng, Ying Liu
BACKGROUND Normothermic machine perfusion (NMP) is a novel strategy used for organ preservation. We aimed to determine the overall efficacy of NMP for liver preservation versus traditional static cold storage (CS). MATERIAL AND METHODS We performed a meta-analysis of the literature to evaluate the efficacy of NMP in experimental pig models of liver preservation. We use the standardized mean difference and 95% confidence intervals (CI) to calculate statistics and used the random effects model for the combined analysis of the results...
March 23, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29559706/uptake-and-accumulation-of-microcystin-lr-based-on-exposure-through-drinking-water-an-animal-model-assessing-the-human-health-risk
#12
Brett Greer, Julie P Meneely, Christopher T Elliott
Harmful Algal Blooms (HABs) in freshwater systems and intensified aquaculture have increased the risk to human health through exposure to cyanotoxins such as microcystin-LR (MC-LR). To understand the uptake and processing of MC-LR in humans, the pig was chosen as an animal model. This was assessed by repeated exposure for 13 weeks of eight animals dosed daily with MC-LR at 0.04 µg/kg bw, repeated with six animals over five weeks at a dose 50 times higher at 2 µg/kg bw. An analytical method was developed for MC-LR in porcine serum and also to analyse levels of free MC-LR in harvested porcine tissues, with Lemieux Oxidation employed to determine bound MC-LR in these tissues...
March 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29538262/overcoming-coagulation-dysregulation-in-pig-solid-organ-transplantation-in-nonhuman-primates-recent-progress
#13
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29519738/alleviating-cyp-and-herg-liabilities-by-structure-optimization-of-dihydrofuran-fused-tricyclic-benzo-d-imidazole-series-potent-selective-and-orally-efficacious-microsomal-prostaglandin-e-synthase-1-mpges-1-inhibitors-part-2
#14
Nagarajan Muthukaman, Sanjay Deshmukh, Macchindra Tambe, Dnyandeo Pisal, Shital Tondlekar, Mahamadhanif Shaikh, Neelam Sarode, Vidya G Kattige, Pooja Sawant, Monali Pisat, Vikas Karande, Srinivasa Honnegowda, Abhay Kulkarni, Dayanidhi Behera, Satyawan B Jadhav, Ramchandra R Sangana, Girish S Gudi, Neelima Khairatkar-Joshi, Laxmikant A Gharat
In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases...
April 15, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29516261/therapeutic-potential-of-bama-miniature-pig-adipose-stem-cells-induced-hepatocytes-in-a-mouse-model-with-acute-liver-failure
#15
Shuang Zhang, Zhiqiang Zhu, Yufeng Wang, Shi Liu, Chenqiong Zhao, Weijun Guan, Yuhua Zhao
The role of mesenchymal stem cells (MSCs) in cellular therapy is well recognized in this work. MSCs have advantages of high proliferation, clone formation, multi-lineage differentiation and immunosuppression. Furthermore, adipose-resident MSCs (ADSCs) are extensively employed due to its advantages of abundant source, low cost and simple operation. Many researchers have emphasized the role of adipose-resident MSCs in the development of therapies for liver injury, but few attentions were paid on the use of induced functional hepatocytes...
March 7, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29511143/development-and-characterization-of-a-guinea-pig-model-for-marburg-virus
#16
Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu
The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model...
January 18, 2018: Zoological Research
https://www.readbyqxmd.com/read/29487593/transglycosylated-starch-modulates-the-gut-microbiome-and-expression-of-genes-related-to-lipid-synthesis-in-liver-and-adipose-tissue-of-pigs
#17
Monica A Newman, Renée M Petri, Dietmar Grüll, Qendrim Zebeli, Barbara U Metzler-Zebeli
Dietary inclusion of resistant starches can promote host health through modulation of the gastrointestinal microbiota, short-chain fatty acid (SCFA) profiles, and lipid metabolism. This study investigated the impact of a transglycosylated cornstarch (TGS) on gastric, ileal, cecal, proximal-colonic, and mid-colonic bacterial community profiles and fermentation metabolites using a growing pig model. It additionally evaluated the effect of TGS on the expression of host genes related to glucose and SCFA absorption, incretins, and satiety in the gut as well as host genes related to lipid metabolism in hepatic and adipose tissue...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29471696/the-recombinant-fusion-protein-cfp10-esat6-difn-has-protective-effect-against-tuberculosis-in-guinea-pigs
#18
Natalya V Permyakova, Pavel A Belavin, Dariya S Pirozhkova, Elena G Ufimtseva, Sergey M Rozov, Sergey R Mursalimov, Yuriy V Sidorchuk, Elena A Uvarova, Alla A Zagorskaya, Tatiana V Marenkova, Svetlana V Bannikova, Evgeniy A Demidov, Konstantin V Starostin, Marionella A Kravchenko, Diana V Vakhrusheva, Roman B Berdnikov, Natalya I Eremeeva, Sergey N Skornyakov, Sergey E Peltek, Elena V Deineko
Development of effective vaccine candidates against tuberculosis is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein ESAT6-CFP10-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute tuberculosis. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response...
February 23, 2018: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29457524/safety-and-effect-on-ablation-size-of-hydrochloric-acid-perfused-radiofrequency-ablation-in-animal-livers
#19
Tian-Qi Zhang, Sen-Miao Huang, Yang-Kui Gu, Fei Gao, Zhi-Mei Huang, Xiong-Ying Jiang, Ding-Xin Liu, Jin-Hua Huang
PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created...
February 26, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29449335/bempedoic-acid-lowers-low-density-lipoprotein-cholesterol-and-attenuates-atherosclerosis-in-low-density-lipoprotein-receptor-deficient-ldlr-and-ldlr-yucatan-miniature-pigs
#20
Amy C Burke, Dawn E Telford, Brian G Sutherland, Jane Y Edwards, Cynthia G Sawyez, P Hugh R Barrett, Roger S Newton, J Geoffrey Pickering, Murray W Huff
OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene targeting has been used to generate Yucatan miniature pigs heterozygous ( LDLR +/- ) or homozygous ( LDLR -/- ) for LDL receptor deficiency (ExeGen)...
May 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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