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https://www.readbyqxmd.com/read/29454797/alterations-in-intestinal-microbiota-lead-to-production-of-interleukin-17-by-intrahepatic-%C3%AE-%C3%AE-t-cell-receptor-positive-cells-and-pathogenesis-of-cholestatic-liver-disease
#1
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ATP binding cassette subfamily B member 4 gene (ABCB4 or MDR2) locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin 17 (IL17), yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29453982/glucagon-like-peptide-1-contributes-to-increases-abca1-expression-by-downregulating-mir-758-to-regulate-cholesterol-homeostasis
#2
Yue Yao, Qiang Li, Ping Gao, Wei Wang, Lili Chen, Jinchao Zhang, Yi Xu
Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453465/screening-of-potential-adipokines-identifies-s100a4-as-a-marker-of-pernicious-adipose-tissue-and-insulin-resistance
#3
Peter Arner, Paul Petrus, David Esteve, Anne Boulomié, Erik Näslund, Anders Thorell, Hui Gao, Ingrid Dahlman, Mikael Rydén
BACKGROUND: Adipokines are peptides secreted from white adipose tissue (WAT), which have been linked to WAT dysfunction and metabolic complications of obesity. We set out to identify novel adipokines in subcutaneous WAT (sWAT) linked to insulin resistance (IR). METHODS: Gene expression was determined by microarray and qPCR in obese and non-obese subjects with varying degree of IR. WAT-secreted and circulating protein levels were measured by ELISA. RESULTS: In sWAT of 80 obese women discordant for IR, 44 genes encoding potential adipose-secreted proteins were differentially expressed...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29446477/atp-sensitive-k-channel-subunits-kir6-1-kir6-2-are-the-candidate-mediators-regulating-ameliorating-effects-of-pulsed-magnetic-field-on-aortic-contractility-in-diabetic-rats
#4
Isil Ocal, Mehmet B Yilmaz, Sabriye Kocaturk-Sel, Turan Tufan, Mehmet A Erkoc, Gamze Comertpay, Hale Oksuz, Esma D Barc
Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (K ATP ) in aortas of controlled-diabetic and non-controlled diabetic rats...
February 15, 2018: Bioelectromagnetics
https://www.readbyqxmd.com/read/29446461/a-method-for-red-blood-cell-biotinylation-in-a-closed-system
#5
Djuna Z de Back, Richard Vlaar, Boukje Beuger, Brunette Daal, Johan Lagerberg, Alexander P J Vlaar, Dirk de Korte, Marian van Kraaij, Robin van Bruggen
BACKGROUND: Several circumstances require the accurate measurement of red blood cell (RBC) survival and clearance, such as determination of posttransfusion recovery of stored RBCs to investigate the effect of new additive solutions. To this end, biotin as a marker of RBCs to track donor RBCs in the blood of the recipient has been used in many studies. However, so far only experimental, nonvalidated, biotin-labeled red cell concentrates (RCCs) are transfused. The goal of this study was to produce a standardized biotin-labeled RCC product in a fast, simple, and sterile manner that can be used for clinical research and for the evaluation of new blood products according to Good Practice Guidelines (GPG) for blood establishments...
February 15, 2018: Transfusion
https://www.readbyqxmd.com/read/29445138/non-toxic-engineered-carbon-nanodiamond-concentrations-induce-oxidative-nitrosative-stress-imbalance-of-energy-metabolism-and-mitochondrial-dysfunction-in-microglial-and-alveolar-basal-epithelial-cells
#6
Claudia G Fresta, Aishik Chakraborty, Manjula B Wijesinghe, Angela M Amorini, Giacomo Lazzarino, Giuseppe Lazzarino, Barbara Tavazzi, Susan M Lunte, Filippo Caraci, Prajnaparamita Dhar, Giuseppe Caruso
Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445117/transitional-correlation-between-inner-membrane-potential-and-atp-levels-of-neuronal-mitochondria
#7
R Suzuki, K Hotta, K Oka
The importance of highly active mitochondria and their contribution to neuronal function has been of recent interest. In most cases, however, mitochondrial activity is estimated using measurements of mitochondrial inner membrane potential (IMP mito ), and little is known about the dynamics of native mitochondrial ATP (ATP mito ). This study conducted simultaneous imaging of IMP mito and ATP mito in neurons to explore their behaviour and their correlation during physiological mitochondrial/neuronal activity...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439712/trovafloxacin-attenuates-neuroinflammation-and-improves-outcome-after-traumatic-brain-injury-in-mice
#8
Charu Garg, Joon Ho Seo, Jayalakshmi Ramachandran, Ji Meng Loh, Frances Calderon, Jorge E Contreras
BACKGROUND: Trovafloxacin is a broad-spectrum antibiotic, recently identified as an inhibitor of pannexin-1 (Panx1) channels. Panx1 channels are important conduits for the adenosine triphosphate (ATP) release from live and dying cells that enhances the inflammatory response of immune cells. Elevated extracellular levels ATP released upon injury activate purinergic pathways in inflammatory cells that promote migration, proliferation, phagocytosis, and apoptotic signals. Here, we tested whether trovafloxacin administration attenuates the neuroinflammatory response and improves outcomes after brain trauma...
February 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29436680/curcumin-increases-cholesterol-efflux-via-heme-oxygenase%C3%A2-1%C3%A2-mediated-abca1-and-sr%C3%A2-bi-expression-in-macrophages
#9
Yi Zhong, Jian Feng, Zhongcai Fan, Jiafu Li
Curcumin, which is an extract from a traditional Chinese medicine, has previously been demonstrated to exhibit an anti‑atherosclerotic effect, which is closely associated with an increase in cholesterol efflux. However, it is unclear as to whether the increased effect is mediated by heme oxygenase (HO)‑1. Macrophages were treated with different concentrations of curcumin, HO‑1 inhibitor and small interfering (si)RNA in different experiments. Analysis of protein expression was conducted via western blotting...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29434725/a-novel-hypothermic-machine-perfusion-system-using-a-lifeport-kidney-transporter-for-the-preservation-of-rat-liver
#10
Cheng Zeng, Xiaoyan Hu, Yanfeng Wang, Xianpeng Zeng, Yan Xiong, Ling Li, Qifa Ye
The protective mechanisms for liver preservation associated with hypothermic machine perfusion (HMP) remain unclear. However, the lack of a common and portable HMP system for rat livers limits the study of HMP. The present study aimed to develop a novel, modified HMP system using a LifePort Kidney Transporter for preserving rat livers. A simple 'Y' shunt combined with a pressoreceptor for flow and pressure regulation was adapted to perfuse rat livers via the portal vein continuously using a LifePort Kidney Transporter under its 'prime mode' setting...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29433569/mh84-improves-mitochondrial-dysfunction-in-a-mouse-model-of-early-alzheimer-s-disease
#11
Maximilian Pohland, Maren Pellowska, Heike Asseburg, Stephanie Hagl, Martina Reutzel, Aljoscha Joppe, Dirk Berressem, Schamim H Eckert, Mario Wurglics, Manfred Schubert-Zsilavecz, Gunter P Eckert
BACKGROUND: Current approved drugs for Alzheimer's disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD...
February 13, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29432725/energy-coupling-efficiency-in-the-type-i-abc-transporter-glnpq
#12
Jelger A Lycklama A Nijeholt, Ruslan Vietrov, Gea K Schuurman-Wolters, Bert Poolman
Solute transport via ABC importers involves receptor-mediated substrate binding, which is followed by ATP-driven translocation of the substrate across the membrane. How these steps are exactly initiated and coupled, and how much ATP it takes to complete a full transport cycle, are subject of debate. Here, we reconstitute the ABC importer GlnPQ in nanodiscs and in proteoliposomes and determine substrate-(in)dependent ATP hydrolysis and transmembrane transport. We determined the conformational states of the substrate-binding domains (SBDs) by single-molecule FRET measurements...
February 9, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29427785/mitochondrial-dysfunction-induced-by-leflunomide-and-its-active-metabolite
#13
Jiekun Xuan, Zhen Ren, Tao Qing, Letha Couch, Leming Shi, William H Tolleson, Lei Guo
Leflunomide, an anti-inflammatory drug used for the treatment of rheumatoid arthritis, has been marked with a black box warning regarding an increased risk of liver injury. The active metabolite of leflunomide, A771726, which also carries a boxed warning about potential hepatotoxicity, has been marketed as teriflunomide for the treatment of relapsing multiple sclerosis. Thus far, however, the mechanism of liver injury associated with the two drugs has remained elusive. In this study, cytotoxicity assays showed that ATP depletion and subsequent LDH release were induced in a time- and concentration-dependent manner by leflunomide in HepG2 cells, and to a lesser extent, by A77 1726...
February 7, 2018: Toxicology
https://www.readbyqxmd.com/read/29426000/d-galactose-induces-premature-senescence-of-lens-epithelial-cells-by-disturbing-autophagy-flux-and-mitochondrial-functions
#14
Yao Xu, Yong Li, Limei Ma, Guang Xin, Zeliang Wei, Zhi Zeng, Zhihua Xing, Shiyi Li, Hai Niu, Wen Huang
Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d-Galactose (d-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d-gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed...
February 6, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29425885/scoping-the-scope-endoscopic-evaluation-of-endoscope-working-channels-with-a-new-high-resolution-inspection-endoscope-with-video
#15
Monique T Barakat, Mohit Girotra, Robert J Huang, Subhas Banerjee
BACKGROUND: Outbreaks of transmission of infection related to endoscopy despite reported adherence to reprocessing guidelines, warrant scrutiny of all potential contributing factors. Recent reports from ambulatory surgery centers indicated widespread significant occult damage within endoscope working channels, raising concerns regarding the potential detrimental impact of this damage on the adequacy of endoscope reprocessing. METHODS: We inspected working channels of all 68 endoscopes at our academic institution using a novel flexible inspection endoscope...
February 6, 2018: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29420962/activation-of-serine-one-carbon-metabolism-by-calcineurin-a%C3%AE-1-reduces-myocardial-hypertrophy-and-improves-ventricular-function
#16
Laura Padrón-Barthe, María Villalba-Orero, Jesús M Gómez-Salinero, Rebeca Acín-Pérez, Sara Cogliati, Marina López-Olañeta, Paula Ortiz-Sánchez, Elena Bonzón-Kulichenko, Jesús Vázquez, Pablo García-Pavía, Nadia Rosenthal, José Antonio Enríquez, Enrique Lara-Pezzi
BACKGROUND: In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES: The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action...
February 13, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29415757/soluble-uric-acid-increases-pdzk1-and-abcg2-expression-in-human-intestinal-cell-lines-via-the-tlr4-nlrp3-inflammasome-and-pi3k-akt-signaling-pathway
#17
Mo Chen, Xiaoyong Lu, Ci Lu, Ning Shen, Yujie Jiang, Menglu Chen, Huaxiang Wu
BACKGROUND: In addition to the kidney, the intestine is one of the most important organs involved in uric acid excretion. However, the mechanism of urate excretion in the intestine remains unclear. Therefore, the relationship between soluble uric acid and the gut excretion in human intestinal cells was explored. The relevant signaling molecules were then also examined. METHODS: HT-29 and Caco-2 cell lines were stimulated with soluble uric acid. Western blotting and qRT-PCR were used to measure protein and mRNA levels...
February 7, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29410610/disruption-of-intracellular-atp-generation-and-tight-junction-protein-expression-during-the-course-of-brain-edema-induced-by-subacute-poisoning-of-1-2-dichloroethane
#18
Gaoyang Wang, Yuan Yuan, Lanyue Gao, Xiaoqiong Tan, Guangqian Yang, Fenghong Zhao, Yaping Jin
The aim of this study was to explore changes in intracellular ATP generation and tight junction protein expression during the course of brain edema induced by subacute poisoning of 1,2-dichloroethane (1,2-DCE). Mice were exposed to 1.2 g/m3 1,2-DCE for 3.5 h per day for 1, 2, or 3 days, namely group A, B, and C. Na+-K+-ATPase and Ca2+-ATPase activity, ATP and lactic acid content, intracellular free Ca2+ concentration and ZO-1 and occludin expression in the brain were measured. Results of present study disclosed that Ca2+-ATPase activities in group B and C, and Na+/K+-ATPase activity in group C decreased, whereas intracellular free Ca2+ concentrations in group B and C increased significantly compared with control...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29410018/linagliptin-potentiates-the-effect-of-l-dopa-on-the-behavioural-biochemical-and-immunohistochemical-changes-in-experimentally-induced-parkinsonism-role-of-toll-like-receptor-4-tgf-%C3%AE-1-nf-%C3%AE%C2%BAb-and-glucagon-like-peptide-1
#19
Ahmed M Kabel, Mohamed S Omar, Abdulrahman Alhadhrami, Salman S Alharthi, Majed M Alrobaian
OBJECTIVE: Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. METHODS: Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day...
January 30, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29408999/hippocampal-mutant-app-and-amyloid-beta-induced-cognitive-decline-dendritic-spine-loss-defective-autophagy-mitophagy-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#20
Maria Manczak, Ramesh Kandimalla, Xiangling Yin, P Hemachandra Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express swedish mutation...
February 1, 2018: Human Molecular Genetics
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