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https://www.readbyqxmd.com/read/28229935/mice-deficient-in-l-12-15-lipoxygenase-show-increased-vulnerability-to-3-nitropropionic-acid-neurotoxicity
#1
Yan He, Rita C Akumuo, Yuan Yang, Sandra J Hewett
Considerable evidence supports a contributory role for leukocyte-type 12/15 Lipoxygenase (L-12/15 LO) in mediating hippocampal and cortical neuronal injury in models of Alzheimer's disease and stroke. Whether L-12/15 LO contributes to neuronal injury in a model of Huntington's disease (HD) has yet to be determined. HD is characterized by marked striatal neuronal loss, which can be mimicked in humans and animals by inhibition of mitochondrial complex II using 3-Nitropropionic acid (3-NP). Herein, we compared histological and behavioral outcomes between mice that were wild-type or null for L-12/15 LO following systemic injection of 3NP...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229632/redox-regulation-of-mitochondrial-functional-activity-by-quinones
#2
N G Krylova, T A Kulahava, V T Cheschevik, I K Dremza, G N Semenkova, I B Zavodnik
Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential...
December 2016: Physiol Int
https://www.readbyqxmd.com/read/28229225/implications-of-sdhb-genetic-testing-in-patients-with-sporadic-pheochromocytoma
#3
Aurelie Maignan, Carole Guerin, Valentin Julliard, Nunzia-Cinzia Paladino, Edward Kim, Philippe Roche, Fréderic Castinetti, Wassim Essamet, Julien Mancini, Alessio Imperiale, Roderick Clifton-Bligh, Pauline Romanet, Anne Barlier, Karel Pacak, Fréderic Sebag, David Taïeb
PURPOSE: Succinate dehydrogenase B (SDHB) associated pheochromocytomas (PHEOs) are associated with a higher risk of tumor aggressiveness and malignancy. The aim of the present study was to evaluate (1) the frequency of germline SDHB mutations in apparently sporadic patients with PHEO who undergo preoperative genetic testing and (2) the ability to predict pathogenic mutations. METHODS: From 2012 to 2016, 82 patients underwent a PHEO surgical resection. Sixteen were operated in the context of hereditary PHEO and were excluded from analysis...
February 22, 2017: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/28229170/molecular-insight-of-arsenic-induced-carcinogenesis-and-its-prevention
#4
REVIEW
Paramita Mandal
Population of India and Bangladesh and many other parts of the world are badly exposed to arsenic through drinking water. Due to non-availability of safe drinking water, they are dependent on arsenic-contaminated water. Generally, poverty level is high in those areas with lack of proper nutrition. Arsenic is considered to be an environmental contaminant and widely distributed in the environment due to its natural existence and anthropogenic applications. Contamination of arsenic in both human and animal could occur through air, soil, and other sources...
February 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28228763/cardiolipin-supports-respiratory-enzymes-in-plants-in-different-ways
#5
Jakob Petereit, Kenta Katayama, Christin Lorenz, Linda Ewert, Peter Schertl, Andreas Kitsche, Hajime Wada, Margrit Frentzen, Hans-Peter Braun, Holger Eubel
In eukaryotes the presence of the dimeric phospholipid cardiolipin (CL) is limited to the mitochondrial membranes. It resides predominantly in the inner membrane where it interacts with components of the mitochondrial electron transfer chain. CL deficiency has previously been shown to affect abundances of the plant NADH-dehydrogenase complex and its association with dimeric cyctochrome c reductase. Using an Arabidopsis thaliana knock-out mutant for the final enzyme of CL biosynthesis we here extend current knowledge on the dependence of plant respiration on CL...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223978/function-and-regulation-of-the-c4-dicarboxylate-transporters-in-campylobacter-jejuni
#6
Marc M S M Wösten, Chris H A van de Lest, Linda van Dijk, Jos P M van Putten
C4-dicarboxylates are important molecules for the human pathogen C.jejuni, as they are used as carbon and electron acceptor molecules, as sugars cannot be utilized by this microaerophilic organism. Based on the genome analysis, C. jejuni may possess five different C4-dicarboxylate transporters: DctA, DcuA, DcuB, and two homologs of DcuC. Here, we investigated the regulation and function of various C4-dicarboxylate transporters in C. jejuni. Transcription of the dctA and dcuC homologs is constitutive, while dcuA and dcuB are both directly regulated by the two-component RacR/RacS system in response to limited oxygen availability and the presence of nitrate...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28223908/elevated-urinary-glyphosate-and-clostridia-metabolites-with-altered-dopamine-metabolism-in-triplets-with-autistic-spectrum-disorder-or-suspected-seizure-disorder-a-case-study
#7
William Shaw
CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate. OBJECTIVE: The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence...
February 2017: Integrative Medicine
https://www.readbyqxmd.com/read/28223797/fabrication-and-in-vitro-in-vivo-evaluation-of-amorphous-andrographolide-nanosuspensions-stabilized-by-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-sodium-lauryl-sulfate
#8
Hongzhi Qiao, Lihua Chen, Tianqi Rui, Jingxian Wang, Ting Chen, Tingming Fu, Junsong Li, Liuqing Di
Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28223260/enhanced-pulmonary-absorption-of-poorly-soluble-itraconazole-by-micronized-cocrystal-dry-powder-formulations
#9
Masatoshi Karashima, Noriyasu Sano, Syunsuke Yamamoto, Yuta Arai, Katsuhiko Yamamoto, Nobuyuki Amano, Yukihiro Ikeda
Micronized cocrystal powders and amorphous spray-dried formulations were prepared and evaluated in vivo and in vitro as pulmonary absorption enhancement formulations of poorly soluble itraconazole (ITZ). ITZ cocrystals with succinic acid (SA) or l-tartaric acid (TA) with a particle size diameter of < 2 µm were successfully micronized using the jet-milling system. The cocrystal crystalline morphologies observed using scanning electron microscopy (SEM) suggested particle shapes that differed from those of the crystalline or spray-dried amorphous ITZ...
February 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28221961/synergistic-antilisterial-effects-of-mixtures-of-lysozyme-and-organic-acids
#10
Myeonggeun Oh, Joongjae Lee, Yoonhwa Jeong, Misook Kim
We investigated the synergistic effects of lysozyme combined with organic acids to inhibit the growth of Listeria monocytogenes . The antilisterial effects of the combination of lysozyme and acetic acid, citric acid, lactic acid, malic acid, or succinic acid were evaluated using the checkerboard method and time-kill assay. The MIC was 25,000 mg/liter for lysozyme, 625 mg/liter for acetic acid, and 1,250 mg/liter for the other acids. The MBC was 10,000 mg/liter for all of the tested organic acids. The combination of lysozyme and each organic acid showed synergistic effects via the checkerboard method; however, the time-kill assay showed synergistic effects for only three combinations of 1,250 mg/liter lysozyme with succinic acid (312 and 625 mg/liter) or malic acid (625 mg/liter)...
December 2016: Journal of Food Protection
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#11
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219662/fumarase-deficiency-causes-protein-and-metabolite-succination-and-intoxicates-mycobacterium-tuberculosis
#12
Nadine Ruecker, Robert Jansen, Carolina Trujillo, Susan Puckett, Pradeepa Jayachandran, Gerardo G Piroli, Norma Frizzell, Henrik Molina, Kyu Y Rhee, Sabine Ehrt
Enzymes of central carbon metabolism are essential mediators of Mycobacterium tuberculosis (Mtb) physiology and pathogenicity, but are often perceived to lack sufficient species selectivity to be pursued as potential drug targets. Fumarase (Fum) is an enzyme of the canonical tricarboxylic acid cycle and is dispensable in many organisms. Transposon mutagenesis studies in Mtb, however, indicate that Fum is required for optimal growth. Here, we report the generation and characterization of a genetically engineered Mtb strain in which Fum expression is conditionally regulated...
February 9, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28216577/qm-hifsa-aided-structure-determination-of-succinilenes-a-d-new-triene-polyols-from-a-marine-derived-streptomyces-sp
#13
Munhyung Bae, So Hyun Park, Yun Kwon, Sang Kook Lee, Jongheon Shin, Joo-Won Nam, Dong-Chan Oh
Based on profiles of secondary metabolites produced by marine bacteria obtained using LC/MS, succinilenes A-D (1-4), new triene polyols, were discovered from a culture of a Streptomyces strain SAK1, which was collected in the southern area of Jeju Island, Republic of Korea. The gross structures of 1-4 were primarily determined through analysis of NMR spectra. The double bond geometries of the succinilenes, which could not be established from conventional ¹H NMR spectra because of the highly overlapped olefinic signals, were successfully deciphered using the recently developed quantum-mechanics-driven ¹H iterative full spin analysis (QM-HiFSA)...
February 14, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28216375/vcpa-a-novel-synthetic-derivative-of-%C3%AE-tocopheryl-succinate-sensitizes-human-gastric-cancer-to-doxorubicin-induced-apoptosis-via-ros-dependent-mitochondrial-dysfunction
#14
Han Wu, Shaoping Liu, Jun Gong, Jiuyang Liu, Qian Zhang, Xiaohua Leng, Nian Zhang, Yan Li
Gastric carcinoma is a common malignant disease worldwide and has a dismal prognosis. Doxorubicin (DOX), one of the most widely used chemotherapeutic agents, has limited use because of its side effects and the development of tumor-cell resistance. Combinations of doxorubicin and non-cross-resistant agents have been required for adjuvant chemotherapy of gastric cancer. Here, we report that VCPA, a novel synthetic derivative of α-Tocopheryl Succinate, induced apoptosis via production of reactive oxygen species (ROS)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28216326/a-scalable-lysyl-hydroxylase-2-expression-system-and-luciferase-based-enzymatic-activity-assay
#15
Hou-Fu Guo, Eun Jeong Cho, Ashwini K Devkota, Yulong Chen, William Russell, George N Phillips, Mitsuo Yamauchi, Kevin N Dalby, Jonathan M Kurie
Hydroxylysine aldehyde-derived collagen cross-links (HLCCs) accumulate in fibrotic tissues and certain types of cancer and are thought to drive the progression of these diseases. HLCC formation is initiated by lysyl hydroxylase 2 (LH2), an Fe(II) and α-ketoglutarate (αKG)-dependent oxygenase that hydroxylates telopeptidyl lysine residues on collagen. Development of LH2 antagonists for the treatment of these diseases will require a reliable source of recombinant LH2 protein and a non-radioactive LH2 enzymatic activity assay that is amenable to high throughput screens of small molecule libraries...
February 16, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28214644/plant-growth-promoting-candida-sp-avgb4-with-capability-of-4-nitroaniline-biodegradation-under-drought-stress
#16
Sivagnanam Silambarasan, Alisa S Vangnai
This study focused on rhizospheric yeast capable of degrading a priority pollutant, 4-nitroaniline (4-NA), under drought stress. Candida sp. AVGB4 (AVGB4) inhabiting in soil was isolated and characterized with plant-growth promoting (PGP) traits. 4-NA-dependent growth kinetic and biodegradation kinetics were analyzed and revealed 4-NA complete degradation and tolerance property. AVGB4 proliferation, PGP activities, and 4-NA degradation activity were well maintained under drought stress induced by PEG-6000 incorporation, and could be strengthened in the presence of succinate, an organic compound generally found in plant root exudates...
February 16, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28214548/global-stability-of-an-%C3%AE-ketoglutarate-dependent-dioxygenase-taud-and-its-related-complexes
#17
Kate L Henderson, Mingjie Li, Salette Martinez, Edwin A Lewis, Robert P Hausinger, Joseph P Emerson
BACKGROUND: TauD is a nonheme iron(II) and α-ketoglutarate (αKG) dependent dioxygenase, and a member of a broader family of enzymes that oxidatively decarboxylate αKG to succinate and carbon dioxide thereby activating O2 to perform a range of oxidation reactions. However before O2 activation can occur, these enzymes bind both substrate and cofactor in an effective manner. Here the thermodynamics associated with substrate and cofactor binding to FeTauD are explored. METHODS: Thermal denaturation of TauD and its enzyme-taurine, enzyme-αKG, and enzyme-taurine-αKG complexes are explored using circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC)...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#18
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
February 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28213850/gamma-hydroxybutyrate-ghb-content-in-hair-samples-correlates-negatively-with-age-in-succinic-semialdehyde-dehydrogenase-deficiency
#19
S S Johansen, X Wang, D Sejer Pedersen, P L Pearl, J-B Roullet, G R Ainslie, K R Vogel, K M Gibson
Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28213099/polymeric-nanoparticles-loaded-with-dexamethasone-or-%C3%AE-tocopheryl-succinate-to-prevent-cisplatin-induced-ototoxicity
#20
Sergio Martín-Saldaña, Raquel Palao-Suay, María Rosa Aguilar, Rafael Ramírez-Camacho, Julio San Román
: The aim of this work is the development of highly protective agents to be administered locally within the middle ear to avoid cisplatin-induced ototoxicity, which affects to 100% of the clinical patients at ultra-high concentrations (16 mg/kg). The protective agents are based on polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate as anti-inflammarory and anti-apoptotic molecules. Dexamethasone and α-tocopheryl succinate are poorly soluble in water and present severe side effects when systemic administered during long periods of time...
February 14, 2017: Acta Biomaterialia
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