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https://www.readbyqxmd.com/read/29475064/ursodeoxycholyl-lysophosphatidylethanolamide-negatively-regulates-tlr-mediated-lipopolysaccharide-response-in-human-thp-1-derived-macrophages
#1
Alzbeta Horvatova, Tanyarath Utaipan, Ann-Christin Otto, Yuling Zhang, Hongying Gan-Schreier, Petr Pavek, Anita Pathil, Wolfgang Stremmel, Walee Chamulitrat
The bile acid-phospholipid conjugate ursodeoxycholyl oleoyl-lysophophatidylethanolamide (UDCA-18:1LPE) is an anti-inflammatory and anti-fibrotic agent as previously shown in cultured hepatocytes and hepatic stellate cells as well as in in vivo models of liver injury. We hypothesize that UDCA-18:1LPE may directly inhibit the activation of immune cells. We found that UDCA-18:1LPE was capable of inhibiting the migration of phorbol ester-differentiated human THP-1 cells. We examined anti-inflammatory activity of UDCA-18:1LPE during activation of THP1-derived macrophages...
February 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29474930/prep1-deficiency-improves-metabolic-response-in-white-adipose-tissue
#2
Antonietta Liotti, Serena Cabaro, Ilaria Cimmino, Serena Ricci, Claudio Procaccini, Orlando Paciello, Gregory A Raciti, Rosa Spinelli, Susanna Iossa, Giuseppe Matarese, Claudia Miele, Pietro Formisano, Francesco Beguinot, Francesco Oriente
Prep1 is a gene encoding for a homeodomain transcription factor which induces hepatic and muscular insulin resistance. In this study, we show that Prep1 hypomorphic heterozygous (Prep1i/+ ) mice, expressing low levels of protein, featured a 23% and a 25% reduction of total body lipid content and epididymal fat, respectively. The percentage of the small adipocytes (25-75 μm) was 30% higher in Prep1i/+ animals than in the WT, with a reciprocal difference in the large adipose cells (100-150 and >150 μm)...
February 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29474740/differences-in-nonclinical-pharmacokinetics-between-species-and-prediction-of-human-pharmacokinetics-of-tak-272-sco-272-a-novel-orally-active-renin-inhibitor
#3
Takuya Ebihara, Mitsuhiro Nishihara, Junzo Takahashi, Fumihiro Jinno, Yoshihiko Tagawa
In the search for orally available drugs, the prediction of human pharmacokinetics (PK) is essential to successfully select compounds that will be clinically useful. This report describes the selection of TAK-272 (SCO-272), a novel orally active renin inhibitor, as a clinical candidate via the detailed investigation of nonclinical PK data and human PK prediction. The bioavailability (BA) of TAK-272 after oral administration to rats and monkeys was low, especially in fasted monkeys, and the systemic exposure of TAK-272 was highly variable in monkeys...
February 23, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29474705/pcb126-inhibits-the-activation-of-ampk-creb-signal-transduction-required-for-energy-sensing-in-liver
#4
Gopi S Gadupudi, Benjamin A Elser, Fabian A Sandgruber, Xueshu Li, Katherine N Gibson-Corley, Larry W Robertson
3,3',4,4',5-pentachlorobiphenyl (PCB126), a dioxin-like PCB, elicits toxicity through a wide array of non-carcinogenic effects, including metabolic syndrome, wasting, and non-alcoholic fatty-liver disease (NAFLD). Previously, we reported decreases in the transcription of several enzymes involved in gluconeogenesis, before the early onset of lipid accumulation. Hence, this study was aimed at understanding the impact of resultant decreases gluconeogenic enzymes on growth, weight and metabolism in the liver, upon extended exposure...
February 20, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29474345/opioid-related-genetic-polymorphisms-do-not-influence-postoperative-opioid-requirement-a-prospective-observational-study
#5
Frédéric Aubrun, Noël Zahr, Olivier Langeron, Nicolas Boccheciampe, Nathalie Cozic, Lisa Belin, Jean-Sebastien Hulot, Frederic Khiami, Bruno Riou
BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics...
February 22, 2018: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/29473340/a-nomogram-incorporating-six-easily-obtained-parameters-to-discriminate-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma
#6
Mengmeng Wang, Yuzhen Gao, Huijuan Feng, Elisa Warner, Mingrui An, Jian'an Jia, Shipeng Chen, Meng Fang, Jun Ji, Xing Gu, Chunfang Gao
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need...
February 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29473269/maternal-viral-load-and-hepatitis-b-virus-mother-to-child-transmission-risk-a-systematic-review-and-meta-analysis
#7
Hong-Lin Chen, Man-Li Zha, Ji-Yu Cai, Gang Qin
OBJECTIVES: The aim of this study was to assess the relationship between maternal viral load and mother-to-child transmission (MTCT) risk in HBeAg-positive mothers. METHODS: PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV) DNA positive and negative group. We also examined the dose-response effect of this relationship. RESULTS: 21 studies with 10,142 mother-child pairs included in the studies...
February 23, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29472923/a-prominent-role-of-interleukin-18-in-acetaminophen-induced-liver-injury-advocates-its-blockage-for-therapy-of-hepatic-necroinflammation
#8
Malte Bachmann, Josef Pfeilschifter, Heiko Mühl
Acetaminophen [paracetamol, N -acetyl- p -aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472690/cisplatin-enhances-hepatitis-b-virus-replication-and-pgc-1%C3%AE-expression-through-endoplasmic-reticulum-stress
#9
Xiaosong Li, E Pan, Junke Zhu, Lei Xu, Xuemei Chen, Jingjing Li, Li Liang, Yuan Hu, Jie Xia, Juan Chen, Wannan Chen, Jieli Hu, Kai Wang, Ni Tang, Ailong Huang
Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29472517/nordihydroguaiaretic-acid-a-lignan-from-larrea-tridentata-creosote-bush-protects-against-alios-diet-induced-metabolic-dysfunction-in-mice
#10
Jackie K W Chan, Stefanie Bittner, Alex Bittner, Suman Atwal, Wen-Jun Shen, Mohammed Inayathullah, Jayakumar Rajada, Mark R R Nicolls, Fredric B Kraemer, Salman Azhar
To determine the effects of NDGA on metabolic and molecular changes in response to feeding mice typical American fast food or Western diet, mice were fed with ALIOS diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to: ALIOS, ALIOS + NDGA, or control diet and maintained on the specific diet for 8 weeks. Mice fed ALIOS diet, showed increased body, liver and epididymal fat pad weight, plasma ALT and AST levels (a measure of liver injury), and liver triglyceride (TG) content. Co-administration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver TG...
February 22, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29471811/ethnic-differences-in-infectious-burden-and-the-association-with-metabolic-risk-factors-for-cardiovascular-disease-a-cross-sectional-analysis
#11
Lara Hartog, Martijn S van Rooijen, Joanne Ujčič-Voortman, Maria Prins, Irene G M van Valkengoed
BACKGROUND: The burden of metabolic risk factors for cardiovascular disease (CVD), such as type 2 diabetes, elevated cholesterol and hypertension, is unequally distributed across ethnic groups. Recent findings suggest an association of infectious burden (IB) and metabolic risk factors, but data from ethnic groups are scarce. Therefore, we investigated ethnic differences in IB and its association with metabolic risk factors. METHODS: We included 440 Dutch, 320 Turkish and 272 Moroccan participants, 18-70 years, of the 2004 general health survey in Amsterdam, the Netherlands...
February 22, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29471671/cholesterol-enriched-membrane-microdomains-are-needed-for-insulin-signaling-and-proliferation-in-hepatic-cells
#12
Matheus de Castro Fonseca, Andressa França, Rodrigo Machado Florentino, Roberta Cristelli Fonseca, Antônio Carlos Melo, Paula Teixeira Vieira Vidigal, André G Oliveira, Laurent Dubuquoy, Michael H Nathanson, M Fátima Leite
Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29471569/does-transjugular-intrahepatic-portosystemic-shunt-stent-differentially-improve-survival-in-a-subset-of-cirrhotic-patients
#13
Jonel Trebicka
Does transjugular intrahepatic portosystemic shunt stent (TIPS) improve survival in a subgroup of patients? Yes. TIPS nearly halves portal pressure and increases the effective blood volume. In cases of acute variceal hemorrhage and with a high risk of treatment failure, defined as either hepatic venous pressure gradient higher than 20 mm Hg, Child B with active bleeding at the endoscopy, or Child C with less than 14 points, early or preemptive placement of TIPS (within 72 hours) improves survival. Also, in suitable patients with intractable or refractory ascites, TIPS improves survival if placed early in the course of treatment...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29471563/hepatic-damage-by-natural-remedies
#14
Raul J Andrade, Inmaculada Medina-Caliz, Andres Gonzalez-Jimenez, Miren Garcia-Cortes, M Isabel Lucena
The rising burden of herbal and dietary supplement hepatotoxicity (HILI) is a growing concern in Western countries. The estimated incidence of HILI in well-designed prospective studies ranges from less than 1 to 3 individuals per 100,000 inhabitants/year. Herbal hepatotoxicity has a particular signature encompassing female predominance, hepatocellular type of damage with markedly elevated transaminases on presentation, more common unintentional rechallenge, and a greater risk of death/liver transplantation...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29471561/nonalcoholic-fatty-liver-disease-in-children
#15
Jake P Mann, Luca Valenti, Eleonora Scorletti, Christopher D Byrne, Valerio Nobili
Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown...
February 2018: Seminars in Liver Disease
https://www.readbyqxmd.com/read/29471013/hepatic-arterial-infusion-of-oxaliplatin-plus-fluorouracil-leucovorin-versus-sorafenib-for-advanced-hepatocellular-carcinoma
#16
Ning Lyu, Yanan Kong, Luwen Mu, Youen Lin, Jibin Li, Yaru Liu, Zhenfeng Zhang, Lie Zheng, Haijing Deng, Shaolong Li, Qiankun Xie, Rongping Guo, Ming Shi, Li Xu, Xiuyu Cai, Peihong Wu, Ming Zhao
BACKGROUND & AIMS: To compare the overall survival (OS) and disease progression free survival (PFS) in patients with advanced hepatocellular carcinoma (Ad-HCC) who are undergoing hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment versus sorafenib. METHODS: This retrospective study was approved by the ethical review committee, and informed consent was obtained from all patients before treatment. HAI of FOLFOX (HAIF) was recommended as an alternative treatment option for patient who refused sorafenib...
February 19, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29470841/disease-duration-and-stage-influence-bone-microstructure-in-patients-with-primary-biliary-cholangitis
#17
Tobias Schmidt, Constantin Schmidt, Felix N Schmidt, Sebastian Butscheidt, Haider Mussawy, Jan Hubert, Thelonius Hawellek, Nicola Oehler, Florian Barvencik, Ansgar W Lohse, Thorsten Schinke, Christoph Schramm, Michael Amling, Tim Rolvien
Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro- and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex and body mass index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the lumbar spine and hip, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess the geometric, volumetric and microstructural changes of bone at the distal radius and tibia...
February 22, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29470354/poor-survival-after-retransplantation-in-nash-cirrhosis
#18
Avesh J Thuluvath, Po-Hung Chen, Paul J Thuluvath, Sergey Kantsevoy, Yulia Savva
BACKGROUND: Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication for liver transplantation (LT) in the U.S. There is a paucity of data on retransplantation (re-LT) in those who were initially transplanted for NASH. METHODS: We queried the UNOS data sets from 2002-2016 to analyze the outcomes of adults with NASH (n=128) and compared them to groups that received re-LT for cryptogenic cirrhosis (CC, n=189), alcoholic cirrhosis (AC, n=300) or autoimmune hepatitis cirrhosis (AIH-C, n=118) after excluding multiple-organ re-LT and individuals with HCC...
February 20, 2018: Transplantation
https://www.readbyqxmd.com/read/29470284/evolving-practice-and-changing-phenotype-in-pediatric-autoimmune-liver-disease-outcomes-from-an-australian-center
#19
Harveen Singh, Fariha Balouch, Charlton Noble, Peter Lewindon
OBJECTIVES: Autoimmune liver disease (AILD) incorporates primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and autoimmune sclerosing cholangitis (ASC). ASC is a condition that includes overlap of AIH and PSC. We investigate changes in practice in relation to diagnosis and phenotype over 2 time periods. METHODS: Retrospective chart review was conducted from January 2000 to 2016. Data were divided into two 8-year cohorts, CI and C2. RESULTS: Data were collected in 75 children, 29 in 2000-2007 (C1) and 46 in 2008-2016 (C2)...
February 21, 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29469770/interstitial-granulomatous-dermatitis-in-a-patient-with-chronic-hepatitis-c-and-mixed-cryoglobulinemia
#20
M Rato, F Gil, A F Monteiro, J Aranha, E Tavares
A 55-year-old man presented with a history of asymptomatic, bilateral, figurate dermatosis consisting of erythematous, annular, linear, andarciform, indurated nodules and plaques on the lateral walls of thorax, flanks, and hypogastrium. His medical history was positive for chronic hepatitis C. Skin biopsy was compatible with the diagnosisof interstitial granulomatous dermatitis. Additionalinvestigation revealed positive rheumatoid factor, antinuclear antibodies, and cryoglobulins. Thepatient started treatment with high-potency topical corticosteroid...
January 15, 2018: Dermatology Online Journal
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