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alpha-1 liver disease

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https://www.readbyqxmd.com/read/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#1
Kezhong Zhang, Hyunbae Kim, Zhiyao Fu, Yining Qiu, Zhao Yang, Jiemei Wang, Deqiang Zhang, Xin Tong, Lei Yin, Jing Li, Jianmei Wu, Nathan R Qi, Sander M Houten, Ren Zhang
BACKGROUND & AIMS: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP by deleting MNADK in mice. METHODS: We generated MNADK-knockout (KO) mice on a C57BL/6NTac background; mice with a wild-type Mnadk gene were used as controls...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#2
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28900996/-clinicopathologic-characteristics-and-prognosis-of-gastric-hepatoid-adenocarcinoma
#3
Rongfei Zhao, Xinxin Wang, Xin Lan, Mingsen Li
OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis, treatment and prognosis of gastric hepatoid adenocarcinoma(HAS). METHODS: Retrospective analysis of clinicopathological data of 24 cases with gastric HAS diagnosed by surgery and pathology in Chinese PLA General Hospital from January 2013 to May 2016 were carried out. All the patients underwent preoperative serum alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), endoscopy and imaging examination (CT or B-mode ultrasonography), and those with elevated AFP were excluded from liver cancer, cirrhosis, endodermal sinus tumor and other diseases...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28899352/integrator-complex-subunit-6-ints6-inhibits-hepatocellular-carcinoma-growth-by-wnt-pathway-and-serve-as-a-prognostic-marker
#4
Ka Yin Lui, Hui Zhao, Chunhui Qiu, Chuo Li, Zhigang Zhang, Haoran Peng, Rongdang Fu, Hu-An Chen, Min-Qiang Lu
BACKGROUND: Integrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015). METHODS: First, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples...
September 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28894050/compounds-of-psoriasis-with-obesity-and-overweight
#5
Agnieszka Owczarczyk-Saczonek, Waldemar Placek
Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28887821/serpina1-and-man1b1-polymorphisms-are-not-linked-to-severe-liver-disease-in-a-french-cohort-of-alpha-1-antitrypsin-deficiency-children
#6
Philippe Joly, Alain Lachaux, Mathias Ruiz, Lioara Restier, Abdelhouaed Belmalih, Colette Chapuis-Cellier, Alain Francina, Céline Renoux, Marion Bouchecareilh
BACKGROUND & AIMS: Fifteen to twenty percent of alpha-1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results. METHODS: Our genotype-phenotype correlation study, performed on 92 ZZ children, aimed at determining once and for all if SERPINA1 and MAN1B1 polymorphisms may be implied in the onset of PHT...
September 8, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28887542/genome-wide-analysis-of-health-related-biomarkers-in-the-uk-household-longitudinal-study-reveals-novel-associations
#7
Bram P Prins, Karoline B Kuchenbaecker, Yanchun Bao, Melissa Smart, Delilah Zabaneh, Ghazaleh Fatemifar, Jian'an Luan, Nick J Wareham, Robert A Scott, John R B Perry, Claudia Langenberg, Michaela Benzeval, Meena Kumari, Eleftheria Zeggini
Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877082/multidisciplinary-management-of-hepatocellular-carcinoma-improves-access-to-therapy-and-patient-survival
#8
Parul D Agarwal, Paulina Phillips, Luke Hillman, Michael R Lucey, Fred Lee, Josh D Mezrich, Adnan Said
BACKGROUND: Given the complexity of managing hepatocellular carcinoma (HCC), it is widely accepted that a multidisciplinary team approach (tumor boards) offers the best approach to individualize therapy. The aim of this study was to determine utilization of therapies and outcomes for patients with HCC, comparing those managed through our multidisciplinary tumor board (MDTB) to those who were not. METHODS: A database analysis of all patients with HCC managed through our MDTB, from 2007 until 2011, was performed...
October 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28837509/a-rare-phenotype-of-alpha-1-antitrypsin-deficiency-due-to-pi-is-in-a-newborn-with-liver-disease
#9
Alice C Huang, Carla Perez, Lina Felipez, Gabriel Chamyan, Milton J Finegold, Erick Hernandez
No abstract text is available yet for this article.
August 23, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28830473/survival-outcomes-of-hepatectomy-for-stage-b-hepatocellular-carcinoma-in-the-bclc-classification
#10
Toshiya Kamiyama, Tatsuya Orimo, Kenji Wakayama, Shingo Shimada, Akihisa Nagatsu, Hideki Yokoo, Hirofumi Kamachi, Kenichiro Yamashita, Tsuyoshi Shimamura, Akinobu Taketomi
BACKGROUND: Because hepatectomy is not recommended in patients with stage B hepatocellular carcinoma (HCC) of the Barcelona Clinic Liver Cancer (BCLC) staging, we evaluated the survival outcomes of hepatectomy for stage B in the BCLC system. METHODS: Data were collected from 297 consecutive adult stage B patients who underwent curative hepatectomy for HCC between 1996 and 2014 in Hokkaido University Hospital. Overall survival (OS), disease-free survival (DFS), and risk factors were analyzed using the Kaplan-Meier method...
August 22, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28818508/the-role-of-the-il-8-signaling-pathway-in-the-infiltration-of-granulocytes-into-the-livers-of-patients-with-alcoholic-hepatitis
#11
S W French, A S Mendoza, N Afifiyan, B Tillman, E Vitocruz, B A French
BACKGROUND AND AIM: IL-8 (C-X-L motif chemokine ligase 8) and CXCR2 (C-X-C-motif chemokine receptor 2) are up regulated in alcoholic hepatitis (AH) liver biopsies. One of the consequences is the attraction and chemotactic neutrophilic infiltrate seen at the AH stage of alcoholic liver disease. MATERIALS AND METHODS: Human formalin-fixed, paraffin-embedded (FFPE) liver biopsies from patients who have AH were studied by (2.1) RNA sequencing, (2.2) PCR and (2.3) semi quantitation of specific proteins in biopsy sections using immunohistochemical measurements of antibody fluorescent intensity with morphometric technology...
August 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28810889/dehydroepiandrosterone-sulfate-and-dehydroepiandrosterone-sulfate-cortisol-ratio-in-cirrhotic-patients-with-septic-shock-another-sign-of-hepatoadrenal-syndrome
#12
Ming-Hung Tsai, Hui-Chun Huang, Yun-Shing Peng, Yung-Chang Chen, Ya-Chung Tian, Chih-Wei Yang, Jau-Min Lien, Ji-Tseng Fang, Cheng-Shyong Wu, Sen-Yung Hsieh, Fa-Yauh Lee
BACKGROUND: Cirrhotic patients are susceptible to sepsis and critical illness-related corticosteroid insufficiency (CIRCI). Dehydroepiandrosterone sulfate (DHEAS) is a corticotropin-dependent adrenal androgen, which has immunostimulating and antiglucocorticoid effects. Considering the synchronized synthesis of cortisol and DHEAS and their opposing effects to each other, investigators have proposed measuring these two hormones as a ratio. Severe sepsis has been associated with low DHEAS, especially relative to high cortisol...
August 15, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28803762/apigenin-protects-against-alcohol-induced-liver-injury-in-mice-by-regulating-hepatic-cyp2e1-mediated-oxidative-stress-and-ppar%C3%AE-mediated-lipogenic-gene-expression
#13
Feng Wang, Jin-Cheng Liu, Rui-Jun Zhou, Xi Zhao, Mei Liu, Hua Ye, Mei-Lin Xie
Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days...
August 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28796993/oral-administration-of-cardioaid-and-lunasin-alleviates-liver-damage-in-a-high-fat-diet-nonalcoholic-steatohepatitis-model
#14
Ariel Drori, Dvorah Rotnemer-Golinkin, Lidya Zolotarov, Yaron Ilan
BACKGROUND: Several of the drugs in development for treatment of nonalcoholic steatohepatitis (NASH) target liver fibrosis or have side effects that prohibit their long-term use in patients with mild to moderate disease. Lunasin is a soy-derived peptide with anti-inflammatory properties. ADM's CardioAid™ is a plant sterol extract that exerts cholesterol- and triacylglycerol-lowering effects. AIM: To determine the immunomodulatory effects of CardioAid and lunasin in a high-fat diet (HFD) animal model of NASH...
2017: Digestion
https://www.readbyqxmd.com/read/28796060/candidate-genes-investigation-for-severe-nonalcoholic-fatty-liver-disease-based-on-bioinformatics-analysis
#15
Shan Qi, Changhong Wang, Chunfu Li, Pu Wang, Minghui Liu
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. However, its etiology and fundamental pathophysiology for the disease process are poorly understood. In this study, we thus used bioinformatics to identify candidate genes potentially causative of severe NAFLD. METHODS: Gene expression profile data GSE49541 were downloaded from the Gene Expression Omnibus database. Tissues samples from 32 severe and 40 mild NAFLD patients were evaluated to identify differentially expressed genes (DEGs) between the 2 groups, followed by analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes pathways...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28752466/therapeutic-options-in-alpha-1-antitrypsin-deficiency-liver-transplantation
#16
Nedim Hadzic
Alpha-1 antitrypsin deficiency is the commonest genetic condition leading to liver transplantation in childhood. It remains unclear why only a minority of individuals carrying homozygous PiZ phenotype has liver disease, but also why of those only about a quarter develops end stage liver disease, requiring liver transplantation. This intervention has now become routine worldwide with 1-year patient survival rates well above 90%. As for all autosomal recessive conditions liver donation from anonymous cadaveric sources is preferred to living related parental donors, due to their presumed heterozygous state...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752463/semiquantitation-of-monomer-and-polymer-alpha-1-antitrypsin-by-centrifugal-separation-and-assay-by-western-blot-of-soluble-and-insoluble-components
#17
Keith S Blomenkamp, Jeffrey H Teckman
Alpha-1 antitrypsin (a1AT) deficiency, in its classical form, is an autosomal recessive disease associated with an increased risk of liver disease in adults and children, and with lung disease in adults. The vast majority of liver disease is associated with homozygosity for the Z mutant allele, also called PiZZ. This homozygous allele synthesizes large quantities of a1AT mutant Z protein in the liver, but the mutant protein also folds improperly during biogenesis. As a result, approximately 85% of the molecules are retained within the hepatocytes instead of being appropriately secreted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752458/measuring-the-effect-of-histone-deacetylase-inhibitors-hdaci-on-the-secretion-and-activity-of-alpha-1-antitrypsin
#18
Chao Wang, Marion Bouchecareilh, William E Balch
Alpha-1 antitrypsin deficiency (AATD) is a protein conformational disease with the most common cause being the Z-variant mutation in alpha-1 antitrypsin (Z-AAT). The misfolded conformation triggered by the Z-variant disrupts cellular proteostasis (protein folding) systems and fails to meet the endoplasmic reticulum (ER) export metrics, leading to decreased circulating AAT and deficient antiprotease activity in the plasma and lung. Here, we describe the methods for measuring the secretion and neutrophil elastase (NE) inhibition activity of AAT/Z-AAT, as well as the response to histone deacetylase inhibitor (HDACi), a major proteostasis modifier that impacts the secretion and function of AATD from the liver to plasma...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752454/periodic-acid-schiff-staining-with-diastase
#19
Dongtao A Fu, Martha Campbell-Thompson
Periodic Acid-Schiff (PAS) with diastase (PAS-D) refers to the use of the PAS stain in combination with diastase, which is an enzyme that digests the glycogen. The purpose of using the PAS-D procedure is to differentiate glycogen from other PAS-positive elements in tissue samples. The PAS-D method is also used for periportal liver staining of AAT polymer inclusions that are seen in alpha-1 antitrypsin deficiency disease. Here, we describe the procedure of PAS-D staining in formalin-fixed, paraffin-embedded human liver tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752452/knockdown-of-z-mutant-alpha-1-antitrypsin-in-vivo-using-modified-dna-antisense-oligonucleotides
#20
Mariam Aghajan, Shuling Guo, Brett P Monia
Alpha-1 antitrypsin (AAT) is a serum protease inhibitor, mainly expressed in and secreted from hepatocytes, important for regulating neutrophil elastase activity among other proteases. Various mutations in AAT cause alpha-1 antitrypsin deficiency (AATD), a rare hereditary disorder that results in liver disease due to accumulation of AAT aggregates and lung disease from excessive neutrophil elastase activity. PiZ transgenic mice contain the human AAT genomic region harboring the most common AATD mutation, the Glu342Lys (Z) point mutation...
2017: Methods in Molecular Biology
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