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'Liver' (1034172)


Feb
2018

Human liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism, is a valid pharmaceutical target for the development of new anti-hyperglycaemic agents for type 2 diabetes. Inhibitor discovery studies have focused on the active site and in particular on glucopyranose based compounds with a β-1 substituent long enough to exploit interactions with a cavity adjacent to the active site, termed the β-pocket. Recently, C-β-d-glucopyranosyl imidazoles and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of hlGP.

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Feb
2018

The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants.

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Feb
2018

Chub (Squalius cephalus) specimens were collected in Korenita River seven months after spillover from the waste water of antimony mine tailing pond and compared with chub living in Kruščica reservoir (intended for water supply) and Međuvršje reservoir (influenced by intense emission of industrial, urban and rural wastewater). Concentrations of 15 elements (Al, As, B, Ba, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Si, Sr, Zn) were determined in muscle, liver and gills of chub by inductively coupled plasma optical spectrometry (ICP-OES) and histopathological alterations in liver and gills were assessed. Chub specimens from Korenita River had higher concentrations of As, Ba and Pb in all three investigated tissues as well as higher total histopathological index values than chub from reservoirs.

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Feb
2018

A major challenge of maintaining primary hepatocytes in vitro is progressive loss of hepatocyte-specific functions, such as protein synthesis and cytochrome P450 (CYP450) catalytic activity. We developed a three-dimensional (3D) nanofibrous scaffold made from poly(L-lactide-co-glycolide) (PLGA) polymer using a newlyoptimizedwet electrospinning techniquethat resulted in a highly porous structure that accommodated inclusion of primary human hepatocytes. Extracellular matrix (ECM) proteins (type I collagen or fibronectin) at varying concentrations were chemically linked to electrospun PLGA using amine coupling to develop an in vitro culture system containing the minimal essential ECM components of the liver micro-environment that preserve hepatocyte function in vitro.

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Feb
2018

The effect of hibernation on oxidative stress and antioxidant defenses was assessed in the frog Nanorana parkeri which inhabits the southern Tibetan Plateau. We compared the indices of oxidative stress (GSSG/GSH), the degree of oxidative damage (content of carbonyl proteins and lipid peroxide products) and the activities of antioxidant enzymes (SOD, CAT, GPx, GST and GR) in liver, brain, heart and muscle of N. parkeri sampled during summer and winter.

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Feb
2018

We compared frequency of the members of B. fragilis group in 100 and 20 colon biopsy specimens of inflammatory bowel disease (IBD) and non-IBD patients. Agar dilution and PCR were orderly used to detect minimal inhibitory concentration of ampicillin, imipenem, and metronidazole, and carriage of related resistance genes cepA, cfi, and nim.

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Feb
2018

Both two-stage hepatectomy (TSH) and one-stage hepatectomy (OSH) represent feasible strategies for resection of advanced bilobar colorectal liver metastases (CLM). However, the influence of the surgical approach on postoperative outcomes and overall survival (OS) is unknown. To define the optimal surgical approach for advanced bilobar CLM requiring right hemihepatectomy, we compared short-term and long-term outcomes following TSH and OSH with contralateral resection or radiofrequency ablation (RFA).

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Feb
2018

Post-hepatectomy liver insufficiency (PHLI) is a significant cause of morbidity and mortality after liver resection. Quantitative imaging analysis using CT scans measures variations in pixel intensity related to perfusion. A preliminary study demonstrated a correlation between quantitative imaging features of the future liver remnant (FLR) parenchyma from preoperative CT scans and PHLI.

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Feb
2018

Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States.
We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5.

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Feb
2018

Lipid peroxidation, glutathione content, glutathione peroxidase activity and gene expression of transcription factors, glutathione peroxidase, glutathione synthetase and glutathione reductase was investigated in common carp liver. Short term (24 h) exposure of aflatoxin Bat different doses (100, 200 and 400 μg AFBkgfeed) was used. It was found that conjugated dienes and trienes elevated after 16 h, while thiobarbituric acid reactive substances content increased only at the lowest dose after 16 and 24 h of exposure.

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Feb
2018

The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative stress markers in bone of male Wistar rats was investigated.

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Feb
2018

Injuries are more morbid and complicated to manage in patients with cirrhosis. However, data are limited regarding the relative risk of injury and severity of injury from falls in patients with cirrhosis compared to those without cirrhosis.
We examined the nationally representative National Emergency Department Sample, an all-payer database including all patients presenting with falls 2009-2012.

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Feb
2018

We aimed to determine the relationship between endocan and cirrhotic cardiomyopathy.
Patients with liver cirrhosis and no heart disease were included in a prospective observational study with liver disease decompensation and death as primary outcomes.
83 cirrhotic patients were included and 32 had cirrhotic cardiomyopathy.

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Jan
2018

Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA) acts by inhibition of hepatic interleukin-8 (IL-8) production in the liver which is one of the main proinflammatory cytokines.

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Mar
2018

The purpose of this study was to compare the efficacy of nucleoside analogues (NAs) in the treatment of HBV-related liver failure. The data of patients with HBV-related liver failure treated with nucleoside analogues were used to conduct a network meta-analysis. A total of 1660 patients from 12 articles about the efficacy of lamivudine, entecavir, telbivudine and tenofovir for HBV-related liver failure treatment were recruited in the study.

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Feb
2018

DNA-dependent protein kinase (DNA-PK) is a very large holoenzyme comprised of the p470 kDa DNA-PK catalytic subunit (DNA-PK) and the Ku heterodimer consisting of the p86 (Ku 80) and p70 (Ku 70) subunits. It is best known for its non-homologous end joining (NHEJ) activity, which repairs double-strand DNA (dsDNA) breaks (DSBs). As expected, the absence of DNA-PK activity results in sensitivity to ionizing radiation, which generates DSBs and defect in lymphocyte development, which requires NHEJ of the V(D)J region in the immunoglobulin and T cell receptor loci.

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Feb
2018

I read with great interest, the manuscript by Hung A et al., recently published in your esteemed journal. As abdominal paracentesis (AP) is considered a relatively safe procedure and done very commonly in evaluating a patient of cirrhosis with ascites, it becomes extremely crucial to carefully select the subset of patients at higher risk of developing post paracentesis hemoperitoneum (PPH).

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Feb
2018

Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits.

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Feb
2018

The most of the hepatitis C-infected patients remain undiagnosed until they develop severe liver damage or submitted for serological screening.
To evaluate a recombinant multiepitope protein for detection of IgG anti-hepatitis C virus.
A synthetic gene was cloned, expressed in Escherichia coli, and the recombinant protein was purified.

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Feb
2018

The significance of pre-operative body composition has recently attracted much attention in various diseases. However, cut-off values for these parameters remain undetermined, and these factors are not currently included in selection criteria for recipients of living donor liver transplantation (LDLT).
Using computed tomography of 657 donors for LDLT, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by using skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR).

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Feb
2018

Probiotics may influence one-carbon (C1) metabolism, neurotransmitters, liver function markers, or behavior.
Male adult Flinders Sensitive Line rats (model of depression, FSL; n = 22) received Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (10or 10colony-forming units/d) or vehicle for 10 weeks. The controls, Flinders Resistant Line rats (FRL, n = 8), only received vehicle.

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Feb
2018

Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation.

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Feb
2018

miR-34a has been shown to be involved in P53 regulation. In this study, we aimed to evaluate the expression level of miR-34a in esophageal cancer and compare it with that of the normal marginal tissues.
Tumor and marginal tissues were obtained from 50 patients with esophageal cancer.

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Feb
2018

Aggressive hepatectomy with venous resection has a higher risk of postoperative liver failure (POLF) than hepatectomy without venous reconstruction; however, venous reconstruction is technically demanding. We performed a novel two-stage hepatectomy (TSH) without venous reconstruction in a patient with bilobar multiple colorectal liver metastases located near the caval confluence, waiting for the development of intrahepatic venous collaterals between procedures.
A 60-year-old man was referred to our hospital with sigmoid colon cancer accompanied by intraabdominal abscess and two synchronous liver metastases.

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Feb
2018

Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities.

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Feb
2018

Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found thatF-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.

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Feb
2018

In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico.
Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.

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Feb
2018

Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD), the progressive expansion of renal cysts, inflammation, and subsequent renal fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal fibrosis and in ADPKD.

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Feb
2018

Worldwide there is variation in prevalence of Hepatitis D viral infection. Superinfection and co infection with hepatitis B viral infection is known to occur in 15-20 million people.
This was a descriptive cross-sectional hospital based study carried out in NAMS, Bir hospital, Kathmandu, Nepal from period of January 2017 to June 2017.

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Feb
2018

Upper gastro-intestinal endoscopy remains the gold standard for screening for esophageal varices but it has its own limitations. It is an invasive, expensive and uncomfortable procedure and needs clinical expertise. Accordingly, this study was conducted to establish the role of non-invasive markers for prediction of esophageal varices in liver cirrhosis.

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Feb
2018

Liver cirrhosis is an important health problem worldwide and is a common disease in Nepal. The profile of cirrhosis may vary due to different factors. This study was undertaken to see the demographic and clinical profiles of patients with cirrhosis of liver attending a tertiary care hospital in Central Nepal.

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Jan
2018

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is increasing. This study evaluated the efficacy of a dietitian-led lifestyle modification programme (D-LMP) to reduce NAFLD in obese adolescents.
Subjects with intra-hepatic triglyceride content (IHTC) equal to or greater than 5% diagnosed by proton-magnetic resonance spectroscopy (H-MRS) were enroled and randomly assigned to either the D-LMP intervention or conventional paediatrician-led consultation (P-CON) group.

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Jan
2018

Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics.
To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr) mice.
Molecular docking simulations of GQ-11, PPARα and PPARγ structures were performed.

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Feb
2018

The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2.

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Feb
2018

Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay.

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Feb
2018

We describe a case of polymicrobial bacterial pericarditis withand, caused by pericardial penetration of the tip of the catheter of a laparoscopic adjustable gastric band (LAGB). The patient developed a cardiac tamponade, and subsequently emergency pericardiocentesis was performed. Analysis of earlier CT scans showed that the tip of the catheter had migrated through the liver and through the diaphragm into the pericardium, and was in contact with the myocardium.

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Feb
2018

Long-term in vitro liver models are now widely explored for human hepatic metabolic clearance prediction, enzyme phenotyping, cross species metabolism, comparison of low clearance drugs as well as induction studies. Here, we present studies using a long-term liver model which show how metabolism and active transport, drug-drug interactions and enzyme induction in healthy and diseased states, e.g.

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Feb
2018

Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D.
A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain.

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Feb
2018

To understand the long-term neurological outcomes and chronological changes of brain MRIs in patients with febrile infection-related epilepsy syndrome (FIRES).
From December 2000 to May 2016, 29 patients diagnosed with FIRES were collected retrospectively. The demographic distribution, clinical manifestations, neuroimaging findings, and treatment methodology were described.

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Feb
2018

Control of viral transcripts as a concept for future HBV therapies.

Curr Opin Virol 2018 Feb 13;30:18-23. Epub 2018 Feb 13.
Christoph Seeger
Chronic hepatitis B virus infections affect over 250 million people world-wide, and, at present, are not curable. Of those, over 800000 are expected to die yearly from complications including cirrhosis and primary hepatocellular carcinoma (HCC). A viral episomal DNA intermediate, covalently closed circular DNA (cccDNA) can persist in nuclei of infected hepatocytes and trigger production of infectious virus.

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Feb
2018

3-(β-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles have been revealed as an effective scaffold for the development of potent glycogen phosphorylase (GP) inhibitors but with the potency very sensitive to the nature of the alkyl/aryl 5-substituent (Kun et al., Eur. J.

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Dec
2017

Normal liver-sparing with proton beam therapy (PBT) allows for dose escalation in the treatment of liver malignancies, but it may result in high doses to the chest wall (CW). CW toxicity (CWT) data after PBT for liver malignancies are limited, with most published reports describing toxicity after a combination of hypofractionated proton and photon radiation therapy. We examined the incidence and associated factors for CWT after hypofractionated PBT for liver malignancies.

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Feb
2018

Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors.

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Feb
2018

To evaluate the radiation dose reduction, image quality and diagnostic confidence with thoraco-abdominopelvic computed tomography (TACT) using a new organ based dose modulation system (liver dose right index [Liver DRI]), compared to TACT using a standard automatic exposure control adjusting mA according to attenuation.
A total of 37 patients who had two TACT examinations on 2 different CT scanners, one using standard automatic exposure control (combination of a DoseRight automatic current selection and Z modulation) and one using Liver DRI were included. There were 19 men and 18 women with a mean age of 67.

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Feb
2018

A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration.

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