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https://www.readbyqxmd.com/read/29425879/retinal-neuroinflammatory-induced-neuronal-degeneration-role-of-toll-like-receptor-4-and-relationship-with-gliosis
#1
Fredrik Ghosh, Hodan Abdshill, Karin Arnér, Ulrikke Voss, Linnéa Taylor
The purpose of this study was to explore retina-intrinsic neuroinflammatory reactions, effects on neuronal survival, relationship with classic gliosis, and possible role of the toll-like receptor 4 (TLR4). To isolate the adult retina from the systemic immune system, a previously described large animal explant culture model was used in which full-thickness porcine retinal sheets can be kept in vitro for extended time periods. Explants were kept for 5 days in vitro (DIV) and were treated with either; lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) inhibitor (CLI-095), LPS + CLI-095, or solvent vehicle throughout the culture period after which retinal sections were examined with hematoxylin and eosin staining and extensive immunohistochemistry...
February 7, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29394503/the-wnt-%C3%AE-catenin-pathway-determines-the-predisposition-and-the-efficiency-of-liver-to-pancreas-reprogramming
#2
Helit Cohen, Hila Barash, Irit Meivar-Levy, Kfir Molakandov, Marina Ben-Shimon, Michael Gurevich, Fatima Zoabi, Adi Har-Zahav, Rolf Gebhardt, Frank Gaunitz, Michael Gurevich, Eytan Mor, Philippe Ravassard, Shoshana Greenberger, Sarah Ferber
Transdifferentiation (TD) is the direct reprogramming of adult cells into cells of alternate fate and function. We were the first to show that liver cells can be transdifferentiated into beta-like, insulin producing cells, by ectopic expression of pancreatic transcription factors (pTFs). However, the efficiency of the process was consistently limited to <15% of the human liver cells treated in culture. The data in the current study suggest that liver to pancreas TD is restricted to a specific population of liver cells that is predisposed to undergo reprogramming...
February 2, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29366429/new-insights-on-ethambutol-targets-in-mycobacterium-tuberculosis
#3
Luciana Dias Ghiraldi-Lopes, Paula Aline Zanetti Campanerut-Sa, Geisa Paulino Caprini Evaristo, Jean Eduardo Meneguello, Adriana Fiorini, Vanessa Pietrowski Baldin, Emanuel Maltempi de Souza, Regiane Bertin de Lima Scodro, Vera Lucia Dias Siqueira, Rosilene Fressatti Cardoso
BACKGROUND: In recent years, very few effective drugs against Mycobacterium tuberculosis (M. tb) have emerged which motivates the research with drugs already used in the treatment of tuberculosis. EMB is a bacteriostatic drug that affects cell wall integrity, but the effects of this drug on bacilli are not fully exploited. OBJECTIVE: Based on the need to better investigate the complex mechanism of action of EMB, our study presented the proteome profile of M. tb after different times of EMB exposure, aiming to comprehend the dynamics of bacilli response to its effects...
January 24, 2018: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-is-governed-by-an-activated-glutamate-dehydrogenase
#4
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear. We investigated how GLP-1 secretion is metabolically coupled in L cells (GLUTag) and in vivo in mice using the insulin-secreting cell line INS-1 832/13 as reference...
March 2018: Diabetes
https://www.readbyqxmd.com/read/29224922/neurons-and-satellite-glial-cells-in-adult-rat-lumbar-dorsal-root-ganglia-express-connexin-36
#5
E Martha Pérez Armendariz, Monica Norcini, Beatriz Hernández-Tellez, Andrés Castell-Rodríguez, Cristina Coronel-Cruz, Raquel Guerrero Alquicira, Alexandra Sideris, Esperanza Recio-Pinto
Previous studies have shown that following peripheral nerve injury there was a downregulation of the gap junction protein connexin 36 (Cx36) in the spinal cord; however, it is not known whether Cx36 protein is expressed in the dorsal root ganglia (DRGs), nor if its levels are altered following peripheral nerve injuries. Here we address these aspects in the adult rat lumbar DRG. Cx36 mRNA was detected using qRT-PCR, and Cx36 protein was identified in DRG sections using immunohistochemistry (IHC) and immunofluorescence (IF)...
December 8, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29196338/proteomics-and-metabolomics-identify-molecular-mechanisms-of-aging-potentially-predisposing-for-chronic-lymphocytic-leukemia
#6
Rupert L Mayer, Josef D Schwarzmeier, Marlene C Gerner, Andrea Bileck, Johanna C Mader, Samuel M Meier-Menches, Samuel M Gerner, Klaus G Schmetterer, Tobias Pukrop, Albrecht Reichle, Astrid Slany, Christopher Gerner
B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, the chronic B cell leukemia cell line JVM-13 was also included. A principal component analysis comprising 6,945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells...
February 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29098096/hbs-sicilian-%C3%AE-%C3%AE-0-thalassemia-a-rare-variant-of-sickle-cell
#7
Grace Onimoe, Genine Smarzo
Sickle cell disease (SCD) is caused by a mutation in the sixth codon of the β-globin gene on chromosome 11, which leads to a single amino acid substitution (glutamine to valine). Sickle-(δβ)0-thalassemia is a rare variant of sickle cell disease (delta-beta thalassemia occurring in association with sickle hemoglobin, HbS), sparsely reported in literature, and has been associated with symptomatology necessitating careful monitoring and follow-up. We describe a patient who presented with a newborn screen reported as "FS" and a negative family history for sickle cell disease and sickle cell trait...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28970582/role-of-the-transforming-growth-factor-%C3%AE-in-regulating-hepatocellular-carcinoma-oxidative-metabolism
#8
Jitka Soukupova, Andrea Malfettone, Petra Hyroššová, María-Isabel Hernández-Alvarez, Irene Peñuelas-Haro, Esther Bertran, Alexandra Junza, Jordi Capellades, Gianluigi Giannelli, Oscar Yanes, Antonio Zorzano, José Carlos Perales, Isabel Fabregat
Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profile of hepatocellular carcinoma (HCC) cells that show differences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without significant differences in glycolytic activity...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911206/identification-of-the-molecular-dysfunction-caused-by-glutamate-dehydrogenase-s445l-mutation-responsible-for-hyperinsulinism-hyperammonemia
#9
Mariagrazia Grimaldi, Melis Karaca, Livia Latini, Estelle Brioudes, Thomas Schalch, Pierre Maechler
Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome gives rise to unregulated protein-induced insulin secretion from pancreatic beta-cells, fasting hypoglycemia and elevated plasma ammonia levels. Mutations associated with HI/HA were identified in the Glud1 gene, encoding for glutamate dehydrogenase (GDH). We aimed at identifying the molecular causes of dysregulation in insulin secretion and ammonia production conferred by the most frequent HI/HA mutation Ser445Leu. Following transduction with adenoviruses carrying the human GDH-wild type or GDH-S445L-mutant gene, immunoblotting showed efficient expression of the transgenes in all the investigated cell types...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28012864/germline-and-somatic-dicer1-mutations-in-familial-and-sporadic-liver-tumors
#10
Stefano Caruso, Julien Calderaro, Eric Letouzé, Jean-Charles Nault, Gabrielle Couchy, Anaïs Boulai, Alain Luciani, Elie-Serge Zafrani, Paulette Bioulac-Sage, Olivier Seror, Sandrine Imbeaud, Jessica Zucman-Rossi
BACKGROUND & AIMS: Growing evidence suggests that genetic predisposition significantly increases the risk of hepatocellular carcinoma (HCC), independently from the presence of other risk factors. Here, we report a novel germline DICER1 mutation associated with familial recurrent liver tumors. We then aimed to investigate the contribution of constitutional and somatic DICER1 mutations on HCC occurrence. METHODS: We investigated two individuals of a single family that developed recurrent well-differentiated hepatocellular tumors over the years...
December 22, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28009836/metabolomics-with-nuclear-magnetic-resonance-spectroscopy-in-a-drosophila-melanogaster-model-of-surviving-sepsis
#11
Veli Bakalov, Roland Amathieu, Mohamed N Triba, Marie-Jeanne Clément, Laura Reyes Uribe, Laurence Le Moyec, Ata Murat Kaynar
Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles...
December 21, 2016: Metabolites
https://www.readbyqxmd.com/read/27989504/morin-and-esculetin-supplementation-modulates-c-myc-induced-energy-metabolism-and-attenuates-neoplastic-changes-in-rats-challenged-with-the-procarcinogen-1-2-dimethylhydrazine
#12
Sharada H Sharma, Senthilkumar Thulasingam, David Raj Chellappan, Prabu Chinnaswamy, Sangeetha Nagarajan
Targeting tumor metabolism by natural products is a novel approach and provides rationale for anti-cancer drug discovery. The present study aims to explore the impact of morin and/or esculetin on c-myc induced energy metabolism in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. In order to achieve this aim we analyzed the expression of glucose and glutamine transporters and the key enzymes of glycolytic pathway besides the markers of neoplastic changes viz., mucin depleted foci (MDF), beta catenin accumulated crypts (BCAC), and markers of cell proliferation viz...
February 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27913195/breast-cancer-derived-extracellular-vesicles-stimulate-myofibroblast-differentiation-and-pro-angiogenic-behavior-of-adipose-stem-cells
#13
Young Hye Song, Christine Warncke, Sung Jin Choi, Siyoung Choi, Aaron E Chiou, Lu Ling, Han-Yuan Liu, Susan Daniel, Marc A Antonyak, Richard A Cerione, Claudia Fischbach
Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting...
July 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27880821/inhibition-of-the-tgf%C3%AE-pathway-enhances-retinal-regeneration-in-adult-zebrafish
#14
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
https://www.readbyqxmd.com/read/27722780/n-acetylcysteine-attenuates-intrauterine-growth-retardation-induced-hepatic-damage-in-suckling-piglets-by-improving-glutathione-synthesis-and-cellular-homeostasis
#15
Hao Zhang, Weipeng Su, Zhixiong Ying, Yueping Chen, Le Zhou, Yue Li, Jingfei Zhang, Lili Zhang, Tian Wang
PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1...
October 8, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27709490/atorvastatin-protects-from-a%C3%AE-1-40-induced-cell-damage-and-depressive-like-behavior-via-probdnf-cleavage
#16
Fabiana K Ludka, Maurício P Cunha, Tharine Dal-Cim, Luisa Bandeira Binder, Leandra C Constantino, Caio M Massari, Wagner C Martins, Ana Lúcia S Rodrigues, Carla I Tasca
Intracerebroventricular (icv) amyloid-beta (Aβ)1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ1-40 infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ1-40-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27586053/aberrant-expression-of-the-pore-forming-katp-channel-subunit-kir6-2-in-hippocampal-reactive-astrocytes-in-the-3xtg-ad-mouse-model-and-human-alzheimer-s-disease
#17
Chelsea M Griffith, Mi-Xin Xie, Wen-Ying Qiu, Andrew A Sharp, Chao Ma, Aihua Pan, Xiao-Xin Yan, Peter R Patrylo
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Recent pharmacologic studies have found that ATP-sensitive potassium (KATP) channels may play a role in AD and could be a potential therapeutic target. Interestingly, these channels are found in both neurons and astrocytes. One of the hallmarks associated with AD is reactive gliosis and a change in astrocytic function has been identified in several neuropathological conditions including AD...
November 12, 2016: Neuroscience
https://www.readbyqxmd.com/read/27457357/the-evolutionary-scope-and-neurological-disease-linkage-of-yeast-prion-like-proteins-in-humans
#18
Lu An, Paul M Harrison
BACKGROUND: Prions are proteinaceous particles that propagate alternative protein conformations/states to further copies of the same proteins, and are transmitted from cell-to-cell, and organism-to-organism. Prions are usually made of the beta-sheet rich assemblies termed amyloid. The original prion protein PrP causes devastating neurodegenerative disorders in humans and other mammals. In the yeast Saccharomyces cerevisiae, many prion-forming proteins have been observed; a prominent feature of these proteins is an intrinsically disordered domain rich in glutamine (Q) and asparagine (N) residues...
July 26, 2016: Biology Direct
https://www.readbyqxmd.com/read/27282920/comparative-leaf-proteomics-of-drought-tolerant-and-susceptible-peanut-in-response-to-water-stress
#19
COMPARATIVE STUDY
Ramesh Katam, Katsumi Sakata, Prashanth Suravajhala, Tibor Pechan, Devaiah M Kambiranda, Karamthot Sivasankar Naik, Baozhu Guo, Sheikh M Basha
UNLABELLED: Water stress (WS) predisposes peanut plants to fungal infection resulting in pre-harvest aflatoxin contamination. Major changes during water stress including oxidative stress, lead to destruction of photosynthetic apparatus and other macromolecules within cells. Two peanut cultivars with diverse drought tolerance characteristics were subjected to WS, and their leaf proteome was compared using two-dimensional electrophoresis complemented with MALDI-TOF/TOF mass spectrometry...
June 30, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27142428/dorsal-root-ganglia-in-friedreich-ataxia-satellite-cell-proliferation-and-inflammation
#20
Arnulf H Koeppen, R Liane Ramirez, Alyssa B Becker, Joseph E Mazurkiewicz
INTRODUCTION: Dorsal root ganglia (DRG) are highly vulnerable to frataxin deficiency in Friedreich ataxia (FA), an autosomal recessive disease due to pathogenic homozygous guanine-adenine-adenine trinucleotide repeat expansions in intron 1 of the FXN gene (chromosome 9q21.11). An immunohistochemical and immunofluorescence study of DRG in 15 FA cases and 12 controls revealed that FA causes major primary changes in satellite cells and inflammatory destruction of neurons. A panel of antibodies was used to reveal the cytoplasm of satellite cells (glutamine synthetase, S100, metabotropic glutamate receptors 2/3, excitatory amino acid transporter 1, ATP-sensitive inward rectifier potassium channel 10, and cytosolic ferritin), gap junctions (connexin 43), basement membranes (laminin), mitochondria (ATP synthase subunit beta and frataxin), and monocytes (CD68 and IBA1)...
May 3, 2016: Acta Neuropathologica Communications
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