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https://www.readbyqxmd.com/read/28404113/pathogenesis-and-novel-treatment-options-for-non-alcoholic-steatohepatitis
#1
REVIEW
Vincent Wai-Sun Wong, Shiv Chitturi, Grace Lai-Hung Wong, Jun Yu, Henry Lik-Yuen Chan, Geoffrey C Farrell
Non-alcoholic fatty liver disease affects 20-40% of the population. Its active form, non-alcoholic steatohepatitis (NASH), is characterised by hepatocyte injury, liver inflammation, and progression of fibrosis, and has emerged as one of the most important causes of liver failure and hepatocellular carcinoma. Weight reduction of 10% by dietary restriction and regular exercise is sufficient to reverse NASH in most patients, but in practice this reduction is often not achieved. Available drugs such as vitamin E, pioglitazone, and pentoxifylline have borderline efficacy, but are limited by potential side-effects and toxicities, and do not improve liver fibrosis...
September 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28365930/hepatocellular-carcinoma-development-in-non-alcoholic-fatty-liver-disease-and-non-alcoholic-steatohepatitis-is-it-going-to-be-the-plague-of-the-21st-century-a-literature-review-focusing-on-pathogenesis-prevention-and-treatment
#2
Chrysoula Argyrou, Demetrios Moris, Spiridon Vernadakis
Liver carcinogenesis in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is a subject of intense research nowadays, since NAFLD is the most common chronic liver disease, affecting a great percentage of the population worldwide, while hepatocellular carcinoma (HCC), which represents the most common primary liver malignancy, is the third leading cause of cancer-related mortality. The underlying pathogenic pathways of both NAFLD and HCC are not completely understood, but there is growing evidence that they share many common pathophysiologic mechanisms and risk factors...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28290069/significance-of-genetic-polymorphisms-in-patients-with-nonalcoholic-fatty-liver-disease
#3
REVIEW
Hisamitsu Miyaaki, Kazuhiko Nakao
Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC)...
March 13, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28290049/type-2-diabetes-and-hepatocellular-carcinoma-risk-factors-and-pathogenesis
#4
REVIEW
P Wainwright, E Scorletti, C D Byrne
PURPOSE OF REVIEW: This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms. RECENT FINDINGS: The presence of type 2 diabetes significantly increases the risk of developing hepatocellular carcinoma, and treatment with metformin may be associated with a lower risk. Treatment with insulin and sulphonylureas may be associated with increased risk...
April 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28287358/intractable-neck-pain-in-an-oncologic-palliative-care-setting-is-cancer-always-the-answer
#5
Valentina Delfine, Enos Bernasconi, Donata Bardelli, Vito Spataro, Tanja Fusi-Schmidhauser
Refractory pain is a common manifestation in an oncologic palliative care setting and represents a major challenge for health care professionals involved in care provision. The underlying neoplasm and its dissemination are the foremost pathophysiologic mechanism for the development of pain in patients with advanced cancer. Nonetheless, other etiologies such as trauma and infections need to be considered by clinicians in this particular care setting. The authors present the case of a patient with a recent diagnosis of hepatocellular carcinoma, suffering from intractable neck pain, progressive worsening of her general conditions, and the onset of a generalized seizure...
March 2017: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/28236701/an-alternative-poldip3-transcript-promotes-hepatocellular-carcinoma-progression
#6
Xiao-Ning Liu, Ji-Hang Yuan, Tian-Tian Wang, Wei Pan, Shu-Han Sun
Alternative splicing plays critical roles in many pathophysiological processes and splicing dysregulation is a hallmark of cancer. The different isoforms may have significantly different effects on cancers. POLDIP3 is a target of ribosomal protein S6 kinase 1, and regulates DNA replication and mRNA translation. In this study, we measured the expression of an alternative POLDIP3 transcript (POLDIP3-β), which lacks exon 3 and 29 amine acids, in clinical hepatocellular carcinoma (HCC) tissues. The roles of POLDIP3-β on HCC cell proliferation, apoptosis, and migration were assessed by Glo cell viability assays, Ethynyl deoxyuridine incorporation assays, colony formation assays, TUNEL assays, Annexin V-propidium iodide staining and flow cytometry, transwell assays, wound healing assays, and in vivo xenograft growth...
February 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28195343/galectin-9-diverse-roles-in-hepatic-immune-homeostasis-and-inflammation
#7
REVIEW
Lucy Golden-Mason, Hugo R Rosen
Glycan-binding proteins which include galectins are involved at all stages of immunity and inflammation, ranging from initiation through resolution. Galectin-9 (Gal-9) is highly expressed in the liver and has a wide variety of biological functions in innate and adaptive immunity that are instrumental in the maintenance of hepatic homeostasis. In the setting of viral hepatitis, increased expression of Gal-9 drives the expansion of regulatory T cells and contraction of effector T cells, thereby favoring viral persistence...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28174483/dual-effect-of-wisp-1-in-diverse-pathological-processes
#8
Mengmeng Feng, Shuqin Jia
Wnt-1 inducible signaling pathway-1 (WISP-1), also known as CCN-4, belongs to the connective tissue growth factor (CTGF) family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer, cholangiocarcinoma, hepatocellular carcinoma and breast cancer...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28163185/genomic-characterization-and-dynamic-methylation-of-promoter-facilitates-transcriptional-regulation-of-h2a-variants-h2a-1-and-h2a-2-in-various-pathophysiological-states-of-hepatocyte
#9
Monica Tyagi, Divya Reddy, Sanjay Gupta
Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28107896/cortisol-levels-in-hair-are-altered-in-irritable-bowel-syndrome-a-case-control-study-in-primary-care
#10
A-K Norlin, S Walter, E Theodorsson, V Tegelstrom, E Grodzinsky, M P Jones, Å Faresjö
OBJECTIVE: Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls. METHODS: In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints...
February 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28104508/exposure-to-high-levels-of-fumarate-and-succinate-leads-to-apoptotic-cytotoxicity-and-altered-global-dna-methylation-profiles-in%C3%A2-vitro
#11
Johannes F Wentzel, Angélique Lewies, Abel J Bronkhorst, Etresia van Dyk, Lissinda H du Plessis, Piet J Pretorius
In the Krebs cycle, succinate is oxidized to fumarate by succinate dehydrogenase (SDH), followed by the conversion of fumarate to malate by fumarate hydratase (FH). In cells with defective SDH and FH, the Krebs cycle is congested, respiration impaired and fumarate and succinate accumulates. Several studies have indicated that the accumulation of these substrates are associated with cytotoxicity and oncogenesis. High levels of succinate and fumarate induce hypoxia inducible factor (HIF1A) hydroxylases, leading to the activation of oncogenic HIF pathways...
April 2017: Biochimie
https://www.readbyqxmd.com/read/28097107/surgical-resection-of-localized-hepatocellular-carcinoma-patient-selection-and-special-consideration
#12
REVIEW
Ka Wing Ma, Tan To Cheung
Localized hepatocellular carcinoma (HCC) refers to a solitary or few tumors located within either the left or right hemiliver without evidence of bilobar or extrahepatic spread. This term encompasses a heterogeneous morphology with no regard to stage of prognosis of the disease. Surgical resection remains the mainstay of curative treatment for the localized HCC. Various biochemical and radiological tests constitute an indispensible part of preoperative assessment. Emergence of laparoscopic hepatectomy has brought liver resection into a new era...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28063004/tubulin-alpha-8-is-expressed-in-hepatic-stellate-cells-and-is-induced-in-transformed-hepatocytes
#13
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Thomas S Weiss, Sabrina Krautbauer, Christa Buechler
Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver...
April 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#14
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/27981611/growth-factor-receptor-binding-protein-14-inhibition-triggers-insulin-induced-mouse-hepatocyte-proliferation-and-is-associated-with-hepatocellular-carcinoma
#15
Lucille Morzyglod, Michèle Caüzac, Lucie Popineau, Pierre-Damien Denechaud, Lluis Fajas, Bruno Ragazzon, Véronique Fauveau, Julien Planchais, Mireille Vasseur-Cognet, Laetitia Fartoux, Olivier Scatton, Olivier Rosmorduc, Sandra Guilmeau, Catherine Postic, Chantal Desdouets, Christèle Desbois-Mouthon, Anne-Françoise Burnol
Metabolic diseases such as obesity and type 2 diabetes are recognized as independent risk factors for hepatocellular carcinoma (HCC). Hyperinsulinemia, a hallmark of these pathologies, is suspected to be involved in HCC development. The molecular adapter growth factor receptor binding protein 14 (Grb14) is an inhibitor of insulin receptor catalytic activity, highly expressed in the liver. To study its involvement in hepatocyte proliferation, we specifically inhibited its liver expression using a short hairpin RNA strategy in mice...
April 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27916167/post-resection-recurrence-of-hepatocellular-carcinoma-in-cirrhotic-patients-is-thrombocytopenia-a-risk-factor-for-recurrence
#16
Ahmed Shehta, Ho-Seong Han, Soyeon Ahn, Yoo-Seok Yoon, Jai Young Cho, Young Rok Choi
PURPOSE: Liver resection is the main treatment for hepatocellular carcinoma (HCC) patients with sufficient liver reserve. However, the long-term outcomes are dismal because the recurrence rate is high, especially in cirrhotic patients. The role of platelets as a predictive factor for HCC recurrence is still controversial. The aim of this study was to assess the influence of the preoperative platelet count on HCC recurrence after liver resection in patients with liver cirrhosis. STUDY DESIGN: Between 2004 and 2013, 233 HCC patients with pathologically proven liver cirrhosis underwent liver resection and were enrolled in this study...
December 2016: Surgical Oncology
https://www.readbyqxmd.com/read/27913395/metabolomic-characterization-of-hepatocellular-carcinoma-in-patients-with-liver-cirrhosis-for-biomarker-discovery
#17
Cristina Di Poto, Alessia Ferrarini, Yi Zhao, Rency S Varghese, Chao Tu, Yiming Zuo, Minkun Wang, Mohammad R Nezami Ranjbar, Yue Luo, Chi Zhang, Chirag S Desai, Kirti Shetty, Mahlet G Tadesse, Habtom W Ressom
BACKGROUND: Metabolomics plays an important role in providing insight into the etiology and mechanisms of hepatocellular carcinoma (HCC). This is accomplished by a comprehensive analysis of patterns involved in metabolic alterations in human specimens. This study compares the levels of plasma metabolites in HCC cases versus cirrhotic patients and evaluates the ability of candidate metabolites in distinguishing the two groups. Also, it investigates the combined use of metabolites and clinical covariates for detection of HCC in patients with liver cirrhosis...
December 2, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27903585/autophagy-in-chronic-liver-diseases-the-two-faces-of-janus
#18
Philippe Gual, Helene Gilgenkrantz, Sophie Lotersztajn
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis, steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (Macroautophagy and Chaperome-mediated autophagy) and chronic liver diseases have been reported...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27899914/how-useful-are-monogenic-rodent-models-for-the-study-of-human-non-alcoholic-fatty-liver-disease
#19
REVIEW
Jake P Mann, Robert K Semple, Matthew J Armstrong
Improving understanding of the genetic basis of human non-alcoholic fatty liver disease (NAFLD) has the potential to facilitate risk stratification of affected patients, permit personalized treatment, and inform development of new therapeutic strategies. Animal models have been widely used to interrogate the pathophysiology of, and genetic predisposition to, NAFLD. Nevertheless, considerable interspecies differences in intermediary metabolism potentially limit the extent to which results can be extrapolated to humans...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27891128/immune-imbalances-in-non-alcoholic-fatty-liver-disease-from-general-biomarkers-and-neutrophils-to-interleukin-17-axis-activation-and-new-therapeutic-targets
#20
REVIEW
Feliciano Chanana Paquissi
Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction...
2016: Frontiers in Immunology
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