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https://www.readbyqxmd.com/read/28092655/circadian-and-upr-dependent-control-of-cpeb4-mediates-a-translational-response-to-counteract-hepatic-steatosis-under-er-stress
#1
Carlos Maillo, Judit Martín, David Sebastián, Maribel Hernández-Alvarez, Mar García-Rocha, Oscar Reina, Antonio Zorzano, Mercedes Fernandez, Raúl Méndez
The cytoplasmic polyadenylation element-binding (CPEB) proteins regulate pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, specific functions in adult organisms are poorly understood. Here we show that CPEB4 is required for adaptation to high-fat-diet- and ageing-induced endoplasmic reticulum (ER) stress, and subsequent hepatosteatosis. Stress-activated liver CPEB4 expression is dual-mode regulated. First, Cpeb4 mRNA transcription is controlled by the circadian clock, and then its translation is regulated by the unfolded protein response (UPR) through upstream open reading frames within the 5'UTR...
January 16, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28090784/effect-of-resveratrol-and-tetracycline-on-the-subacute-paraquat-toxicity-in-mice
#2
R M Satpute, P P Pawar, S Puttewar, S D Sawale, P D Ambhore
Paraquat (PQ) is a nonselective bipyridyl herbicide widely used in agriculture to control weeds, but its accidental, occupational, or intentional exposure in humans is known to cause pneumo- and neurotoxicity which may proves fatal. Oxidative stress is reported as an underlined mechanism of PQ-induced toxicity in alveolar cells, neurons, and astroglia. PQ generates superoxides both through electron transport reaction (ETC) with nicotinamide adenine dinucleotide-dependent oxidoreductase and by the redox cycling via reaction with molecular oxygen...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28089782/hepatic-co-cultures-in-vitro-reveal-suitable-to-detect-nrf2-mediated-oxidative-stress-responses-on-the-bladder-carcinogen-o-anisidine
#3
Franziska Wewering, Florent Jouy, Sükran Caliskan, Stefan Kalkhof, Martin von Bergen, Andreas Luch, Sebastian Zellmer
The azo dye o-anisidine is known as an industrial and environmental pollutant. Metabolites of o-anisidine remain in the liver for >24h. However, the toxicological impact of o-anisidine on the liver and its individual cell types, e.g., hepatocytes and immune cells, is currently poorly understood. A novel co-culture system, composed of HepG2 or Huh-7 cells, and differentiated THP-1 cells was used to study the metabolic capacity towards o-anisidine, and compared to primary murine hepatocytes which express high enzyme activities...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28088642/anti-rage-antibody-selectively-blocks-acute-systemic-inflammatory-responses-to-lps-in-serum-liver-csf-and-striatum
#4
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Henrique Schaan Fernandes, Alexsander Alves Teixeira, Marcelo Otavio Rodrigues Guasselli, Crepin Aziz Jose O Agani, Natália Cabral Souza, Mateus Grings, Guilhian Leipnitz, Henrique Mautone Gomes, Matheus Augusto de Bittencourt Pasquali, Peter R Dunkley, Phillip W Dickson, José Claudio Fonseca Moreira, Daniel Pens Gelain
Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50 μg/kg) was followed after 1h by a single LPS (5 mg/kg) intraperitoneal injection...
January 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28088395/lactate-and-lactate-pyruvate-ratio-in-the-diagnosis-and-outcomes-of-pediatric-acute-liver-failure
#5
Amy G Feldman, Ronald J Sokol, Regina M Hardison, Estella M Alonso, Robert H Squires, Michael R Narkewicz
OBJECTIVES: To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P  ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days. STUDY DESIGN: Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day...
January 12, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28086886/biochemical-mechanism-underlying-hypertriglyceridemia-and-hepatic-steatosis-hepatomegaly-induced-by-acute-schisandrin-b-treatment-in-mice
#6
Yi Zhang, Jing Zhao, Shu-Feng Zhou, Zhi-Ling Yu, Xiao-Yan Wang, Pei-Li Zhu, Zhu-Sheng Chu, Si-Yuan Pan, Ming Xie, Kam-Ming Ko
BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0...
January 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28077841/pars2-and-nars2-mutations-in-infantile-onset-neurodegenerative-disorder
#7
Takeshi Mizuguchi, Mitsuko Nakashima, Mitsuhiro Kato, Keitaro Yamada, Tohru Okanishi, Nina Ekhilevitch, Hanna Mandel, Ayelet Eran, Miyuki Toyono, Yukio Sawaishi, Hirotaka Motoi, Masaaki Shiina, Kazuhiro Ogata, Satoko Miyatake, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto
Here we present four unrelated families with six individuals that have infantile-onset developmental delay/regression and epilepsy. Whole-exome sequencing revealed compound heterozygous mutations, c.[283G>A];[607G>A] in a gene encoding prolyl-tRNA synthetase (PARS2) in one family. Two pairs of compound heterozygous mutations, c.[151C>T];[1184T>G] and c.[707T>G];[594+1G>A], and a homozygous mutation, c.[500A>G];[500A>G], in a gene encoding asparaginyl-tRNA synthetase (NARS2) were also identified in the other three families...
January 12, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28077390/reversible-temperature-dependent-differences-in-brown-adipose-tissue-respiration-during-torpor-in-a-mammalian-hibernator
#8
Sarah Victoria McFarlane, Katherine E Mathers, James F Staples
While seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal an°°d interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free-fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#9
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28076839/chemotherapy-can-induce-weight-normalization-of-morbidly-obese-mice-despite-undiminished-ingestion-of-high-fat-diet
#10
Cheryl E Myers, Dominique B Hoelzinger, Tiffany N Truong, Lindsey A Chew, Arpita Myles, Leena Chaudhuri, Jan B Egan, Jun Liu, Sandra J Gendler, Peter A Cohen
Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073422/-research-advances-in-the-association-between-deacetylase-sirtuin3-and-liver-diseases
#11
J Yu, C Chen, W X Wang
The deacetylase Sirtuin 3 (SIRT3) is a member of the Sirtuins mainly located in the mitochondrial matrix, and as a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, it can regulate cellular energy metabolism and oxidative stress-related pathways. The liver is the largest solid organ in the human body and plays a very important role in substance metabolism. Based on the features of SIRT3, it is closely associated with the development and progression of certain liver diseases. This article reviews the research advances in the role of SIRT3 in non-alcoholic fatty liver disease, liver cancer, and hepatic ischemia-reperfusion injury...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28070860/energetic-oxidative-and-ionic-exchange-in-rat-brain-and-liver-mitochondria-at-experimental-audiogenic-epilepsy-krushinsky-molodkina-model
#12
Natalya I Venediktova, Olga S Gorbacheva, Natalia V Belosludtseva, Irina B Fedotova, Natalia M Surina, Inga I Poletaeva, Oleg V Kolomytkin, Galina D Mironova
The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats...
January 9, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28070495/an-atypical-presentation-of-acad9-deficiency-diagnosis-by-whole-exome-sequencing-broadens-the-phenotypic-spectrum-and-alters-treatment-approach
#13
H K Aintablian, V Narayanan, N Belnap, K Ramsey, T A Grebe
Acyl-CoA dehydrogenase 9 (ACAD9), linked to chromosome 3q21.3, is one of a family of multimeric mitochondrial flavoenzymes that catalyze the degradation of fatty acyl-CoA from the carnitine shuttle via β-oxidation (He et al. 2007). ACAD9, specifically, is implicated in the processing of palmitoyl-CoA and long-chain unsaturated substrates, but unlike other acyl-CoA dehydrogenases (ACADs), it has a significant role in mitochondrial complex I assembly (Nouws et al. 2010 & 2014). Mutations in this enzyme typically cause mitochondrial complex I deficiency, as well as a mild defect in long chain fatty acid metabolism (Haack et al...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#14
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28062951/the-effect-of-selenium-on-the-cd-induced-apoptosis-via-no-mediated-mitochondrial-apoptosis-pathway-in-chicken-liver
#15
Runxiang Zhang, Ran Yi, Yanju Bi, Lu Xing, Jun Bao, Jianhong Li
Cd-induced apoptosis and the protective effects of Se against Cd-induced injury have been reported in previous studies. However, little is known regarding the effects of Cd-induced apoptosis in hepatic cells and the antagonistic effects of Se on Cd in poultry. In the present study, 128 healthy 31-week-old laying hens were randomly divided into four groups, which were fed basic diets, with the addition of Se (Na2SeO3, 2 mg/kg), Cd (CdCl2, 150 mg/kg), or Se + Cd (150 mg/kg of CdCl2 and 2 mg/kg of Na2SeO3) for 90 days...
January 6, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28059952/atp-citrate-lyase-genetics-molecular-biology-and-therapeutic-target-for-dyslipidemia
#16
Amy C Burke, Murray W Huff
PURPOSE OF REVIEW: ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition. RECENT FINDINGS: ACLY is a critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis. Human genetic variants have been associated with enhanced growth and survival of several cancers, and with attenuated plasma triglyceride responses to dietary fish oil...
January 5, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28059524/antileishmanial-activity-of-pyrazolopyridine-derivatives-and-their-potential-as-adjunct-therapy-with-miltefosine
#17
Devireddy Anand, Pawan Kumar Yadav, Om P S Patel, Naveen Parmar, Rahul K Maurya, Preeti Vishwakarma, Kanumuri S R Raju, Isha Taneja, Muhammad Wahajuddin, Susanta Kar, Prem P Yadav
A series of pyrazolo(dihydro)pyridines were synthesized and evaluated for antileishmanial efficacy against experimental visceral leishmaniasis. Among all, compounds 6d and 6j exhibited better activity than miltefosine against the intracellular amastigotes. Compound 6j (50 mg/kg/day) was further studied against Leishmania donovani/BALB/c mice via the intraperitoneal route for 5 days and displayed >91 and >93% clearances in splenic and liver parasitic burden, respectively. Combination treatment of 6j with the sub-curative dose of miltefosine (5 mg/kg) in BALB/c mice almost completely ameliorated the disease (>97% inhibition) by augmenting nitric oxide generation and shifting the immune response towards Th1 mode...
January 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28059170/in-ovo-injection-of-betaine-alleviates-corticosterone-induced-fatty-liver-in-chickens-through-epigenetic-modifications
#18
Yun Hu, Qinwei Sun, Jie Liu, Yimin Jia, Demin Cai, Abdulrahman A Idriss, Nagmeldin A Omer, Ruqian Zhao
Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28058631/induction-of-apoptosis-of-liver-cancer-cells-by-nanosecond-pulsed-electric-fields-nspefs
#19
Ling He, Deyou Xiao, Jianguo Feng, Chenguo Yao, Liling Tang
The application of nanosecond pulsed electric fields (nsPEFs) is a novel method to induce the death of cancer cells. NsPEFs could directly function on the cell membrane and activate the apoptosis pathways, then induce apoptosis in various cell lines. However, the nsPEFs-inducing-apoptosis action sites and the exact pathways are not clear now. In this study, nsPEFs were applied to the human liver cancer cells HepG2 with different parameters. By apoptosis assay, morphological observation, detecting the mitochondrial membrane potential (ΔΨ m), intracellular calcium ion concentration ([Ca(2+)]i) and the expressions of key apoptosis factors, we demonstrated that nsPEFs could induce the morphology of cell apoptosis, the change in ΔΨ m, [Ca(2+)]i and the upregulation of some key apoptosis factors, which revealed the responses of liver cancer cells and indicated that cells may undergo apoptosis through the mitochondria-dependent pathway after nsPEFs were applied...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28055957/analysis-of-molecular-mechanisms-of-5-fluorouracil-induced-steatosis-and-inflammation-in-vitro-and-in-mice
#20
Judith Sommer, Abdo Mahli, Kim Freese, Tobias S Schiergens, Fulya Suzan Kuecuekoktay, Andreas Teufel, Wolfgang E Thasler, Martina Müller, Anja K Bosserhoff, Claus Hellerbrand
Chemotherapy-associated steatohepatitis is attracting increasing attention because it heralds an increased risk of morbidity and mortality in patients undergoing surgery because of liver metastases. The aim of this study was to develop in vitro and in vivo models to analyze the pathogenesis of 5-fluorouracil (5-FU)-induced steatohepatitis.Therefore, primary human hepatocytes and HepG2 hepatoma cells were incubated with 5-FU at non-toxic concentrations up to 24 h. Furthermore, hepatic tissue of C57BL/6N mice was analyzed 24 h after application of a single 5-FU dose (200 mg/kg body weight)...
December 30, 2016: Oncotarget
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