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https://www.readbyqxmd.com/read/29786646/metabolic-reprogramming-by-3-iodothyronamine-t1am-a-new-perspective-to-reverse-obesity-through-co-regulation-of-sirtuin-4-and-6-expression
#1
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29785262/evaluation-of-the-relevance-of-dili-predictive-hypotheses-in-early-drug-development-review-of-in-vitro-methodologies-vs-bddcs-classification
#2
Rosa Chan, Leslie Z Benet
Drug-induced liver injury (DILI) is a major safety concern; it occurs frequently; it is idiosyncratic; it cannot be adequately predicted; and a multitude of underlying mechanisms has been postulated. A number of experimental approaches to predict human DILI have been proposed utilizing in vitro screening such as inhibition of mitochondrial function, hepatobiliary transporter inhibition, reactive metabolite formation with and without covalent binding, and cellular health, but they have achieved only minimal success...
May 8, 2018: Toxicology Research
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#3
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29783990/severe-hepatopathy-and-neurological-deterioration-after-start-of-valproate-treatment-in-a-6-year-old-child-with-mitochondrial-tryptophanyl-trna-synthetase-deficiency
#4
Elise Vantroys, Joél Smet, Arnaud V Vanlander, Sarah Vergult, Ruth De Bruyne, Frank Roels, Hedwig Stepman, Herbert Roeyers, Björn Menten, Rudy Van Coster
BACKGROUND: The first subjects with deficiency of mitochondrial tryptophanyl-tRNA synthetase (WARS2) were reported in 2017. Their clinical characteristics can be subdivided into three phenotypes (neonatal phenotype, severe infantile onset phenotype, Parkinson-like phenotype). RESULTS: Here, we report on a subject who presented with early developmental delay, motor weakness and intellectual disability and who was considered during several years as having a non-progressive encephalopathy...
May 21, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#5
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29782848/impaired-tfeb-mediated-lysosome-biogenesis-and-autophagy-promote-chronic-ethanol-induced-liver-injury-and-steatosis-in-mice
#6
Xiaojuan Chao, Shaogui Wang, Katrina Zhao, Yuan Li, Jessica A Williams, Tiangang Li, Hemantkumar Chavan, Partha Krishnamurthy, Xi C He, Linheng Li, Andrea Ballabio, Hong-Min Ni, Wen-Xing Ding
BACKGROUND & AIMS: Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. METHODS: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfebflox/flox albumin cre-negative mice (controls)...
May 18, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29779728/association-between-aldehyde-dehydrogenase-2-glu504lys-polymorphism-and-alcoholic-liver-disease
#7
Binxia Chang, Shuli Hao, Longyu Zhang, Miaomiao Gao, Ying Sun, Ang Huang, Guangju Teng, Baosen Li, David W Crabb, Praveen Kusumanchi, Li Wang, Suthat Liangpunsakul, Zhengsheng Zou
BACKGROUND: Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD), though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases...
March 20, 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29777756/peroxiredoxin-5-regulates-adipogenesis-attenuating-oxidative-stress-in-obese-mouse-models-induced-by-a-high-fat-diet
#8
Mi Hye Kim, Sun-Ji Park, Jung-Hak Kim, Jung Bae Seong, Kyung-Min Kim, Hyun Ae Woo, Dong-Seok Lee
Elevated levels of reactive oxygen species (ROS) are a hallmark of obesity. Peroxiredoxin 5 (Prx5), which is a cysteine-dependent peroxidase enzyme, has an intensive ROS scavenging activity because it is located in the cytosol and mitochondria. Therefore, we focused on the role of Prx5 in regulating mitochondrial ROS and adipogenesis. We demonstrated that Prx5 expression was upregulated during adipogenesis and Prx5 overexpression suppressed adipogenesis by regulating cytosolic and mitochondrial ROS generation...
May 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29775890/triterpenic-acids-enriched-fraction-from-cyclocarya-paliurus-attenuates-non-alcoholic-fatty-liver-disease-via-improving-oxidative-stress-and-mitochondrial-dysfunction
#9
Meng-Ge Zhao, Xue-Ping Sheng, Ya-Ping Huang, Yi-Ting Wang, Cui-Hua Jiang, Jian Zhang, Zhi-Qi Yin
The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#10
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29773865/perlecan-a-heparan-sulfate-proteoglycan-regulates-systemic-metabolism-with-dynamic-changes-in-adipose-tissue-and-skeletal-muscle
#11
Yuri Yamashita, Satoshi Nakada, Toshinori Yoshihara, Takeshi Nara, Norihiko Furuya, Takashi Miida, Nobutaka Hattori, Eri Arikawa-Hirasawa
Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2-/- -Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2-/- -Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773670/high-%C3%AE-tocopherol-dosing-increases-lipid-metabolism-by-changing-redox-state-in-damaged-rat-gastric-mucosa-and-liver-after-ethanol-treatment
#12
Marisela Olguín-Martínez, Diego R Hernández-Espinosa, Rolando Hernández-Muñoz
Regeneration of ethanol-injured rat gastric mucosa must undergo changes in major metabolic pathways to achieve DNA replication and cell proliferation. These events are highly dependent on glucose utilization and inhibited by vitamin E (α-tocopherol) administration. Therefore, this study was aimed at assessing lipid metabolism in the gastric mucosa and ethanol-induced gastric damage and the effect of α-tocopherol administration. For this, rates of fatty acid β-oxidation and lipogenesis were tested in gastric mucosa samples...
May 17, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29773653/inhibition-of-protein-arginine-methyltransferase-5-enhances-hepatic-mitochondrial-biogenesis
#13
Lei Huang, Jehnan Liu, Xiao-Ou Zhang, Katelyn Sibley, Sonia M Najjar, Mary M Lee, Joae Qiong Wu
Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionallyly by symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3, or at the post-translational level by methylation of non-histone target proteins. While emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well defined. We investigated the role of PRMT5 in promoting high fat-induced hepatic steatosis. High fat diet up-regulated PRMT5 levels in the liver, but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29773145/pathological-and-molecular-characterization-of-systemic-isosporosis-atoxoplasmosis-in-captive-green-winged-saltator-saltator-similis
#14
Ayisa Rodrigues de Oliveira, Tayse Domingues de Souza, Juliana P S Mol, Mayra Cunha Flecher, Emy Hiura, Renato Lima Santos
Systemic isosporosis, also called atoxoplasmosis or visceral coccidiosis, is a disease that affects birds in general. Pathogenesis of systemic isosporosis and its etiologic agent have not been well characterized, but taxonomically Atoxoplasma is currently considered a junior objective synonym of Isospora. The present report aimed to describe pathological and molecular findings of systemic isosporosis in captive green-winged saltators (Saltator similis) from the State of Espírito Santo, Brazil. In a commercial breeding facility eleven birds with two to nine months of age died from 2015 to 2016...
May 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29772216/human-liver-fluke-opisthorchis-viverrini-trematoda-opisthorchiidae-in-central-myanmar-new-records-of-adults-and-metacercariae-identified-by-morphology-and-molecular-analysis
#15
Oranuch Sanpool, Win Pa Pa Aung, Rutchanee Rodpai, Wanchai Maleewong, Pewpan M Intapan
Opisthorchis-like metacercariae were found in cyprinoid fish, Puntius brevis, bought from markets in the Bago region, Central Myanmar. Adult worms recovered from experimentally-infected hamsters resembled Opisthorchis viverrini. DNA was extracted from adults and metacercariae. A portion of the mitochondrial cytochrome c oxidase subunit 1 (cox1) and the internal transcribed spacer 2 (ITS2) regions were amplified using the polymerase chain reaction and then sequenced. The sequences confirmed that the flukes were O...
May 14, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29771992/first-description-of-echinococcus-ortleppi-and-cystic-echinococcosis-infection-status-in-chile
#16
Felipe Corrêa, Caroll Stoore, Pamina Horlacher, Mauricio Jiménez, Christian Hidalgo, Cristian A Alvarez Rojas, Guilherme Figueiredo Barros, Henrique Bunselmeyer Ferreira, Marcela Hernández, Gonzalo Cabrera, Rodolfo Paredes
Cystic echinococcosis (CE), a parasitic disease caused by the cestode Echinococcus granulosus sensu lato (s.l.), is a worldwide zoonotic infection. Although endemic in Chile, information on the molecular characteristics of CE in livestock remains scarce. Therefore we aimed to describe the status of infection with E. granulosus s.l. in cattle from central Chile and also to contribute to the study of the molecular epidemiology of this parasite. According to our results, the prevalence of CE is 18.84% in cattle, similar to previous reports from Chile, suggesting that the prevalence in Santiago Metropolitan area has not changed in the last 30 years...
2018: PloS One
https://www.readbyqxmd.com/read/29767974/in-vitro-and-in-vivo-demonstration-of-human-ovarian-cancer-necrosis-through-a-water-soluble-and-near-infrared-absorbing-chlorin
#17
Betsy Marydasan, Bollapalli Madhuri, Shirisha Cherukommu, Jedy Jose, Mambattakkara Viji, Suneesh C Karunakaran, Tavarekere K Chandrashekar, Kunchala Sridhar Rao, Ch Mohan Rao, Danaboyina Ramaiah
With an objective to develop efficient sensitizers for therapeutical applications, we synthesized a water soluble, 5,10,15,20-tetrakis(3,4-dihydroxyphenyl)chlorin (TDC), and investigated its in vitro and in vivo biological efficacy and compared with the commercially available sensitizers. TDC showed high water solubility (6-fold), when compared to Foscan and exhibited excellent triplet excited state () and singlet oxygen () yields. In vitro photobiological investigations in human ovarian cancer cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity, rapid cellular uptake and specific localization of TDC in neoplastic cells as assessed by flow cytometric cell-cycle and propidium iodide staining analysis...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29767698/mechanisms-by-which-dietary-fatty-acids-regulate-mitochondrial-structure-function-in-health-and-disease
#18
E Madison Sullivan, Edward Ross Pennington, William D Green, Melinda A Beck, David A Brown, Saame Raza Shaikh
Mitochondria are the energy-producing organelles within a cell. Furthermore, mitochondria have a role in maintaining cellular homeostasis and proper calcium concentrations, building critical components of hormones and other signaling molecules, and controlling apoptosis. Structurally, mitochondria are unique because they have 2 membranes that allow for compartmentalization. The composition and molecular organization of these membranes are crucial to the maintenance and function of mitochondria. In this review, we first present a general overview of mitochondrial membrane biochemistry and biophysics followed by the role of different dietary saturated and unsaturated fatty acids in modulating mitochondrial membrane structure-function...
May 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29767695/molybdenum
#19
Janet A Novotny, Catherine A Peterson
Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for lead, molybdenum was named after the Greek work molybdos, meaning lead-like. In the 1930s, it was recognized that ingestion of forage with high amounts of molybdenum by cattle caused a debilitating condition. In the 1950s, the essentiality of molybdenum was established with the discovery of the first molybdenum-containing enzymes. In humans, only 4 enzymes requiring molybdenum have been identified to date: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime-reducing component (mARC)...
May 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29767564/interorgan-metabolic-crosstalk-in-human-insulin-resistance
#20
Sofiya Gancheva, Tomas Jelenik, Elisa Álvarez-Hernández, Michael Roden
Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism...
July 1, 2018: Physiological Reviews
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