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https://www.readbyqxmd.com/read/29453370/a-multitarget-approach-to-drug-discovery-inhibiting-mycobacterium-tuberculosis-pyrg-and-pank
#1
Laurent R Chiarelli, Giorgia Mori, Beatrice Silvia Orena, Marta Esposito, Thomas Lane, Ana Luisa de Jesus Lopes Ribeiro, Giulia Degiacomi, Júlia Zemanová, Sára Szádocka, Stanislav Huszár, Zuzana Palčeková, Marcello Manfredi, Fabio Gosetti, Joël Lelièvre, Lluis Ballell, Elena Kazakova, Vadim Makarov, Emilio Marengo, Katarina Mikusova, Stewart T Cole, Giovanna Riccardi, Sean Ekins, Maria Rosalia Pasca
Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452236/cardiac-and-placental-mitochondrial-characterization-in-a-rabbit-model-of-intrauterine-growth-restriction
#2
M Guitart-Mampel, A Gonzalez-Tendero, S Niñerola, C Morén, M Catalán-Garcia, I González-Casacuberta, D L Juárez-Flores, O Ugarteburu, L Matalonga, M V Cascajo, F Tort, A Cortés, E Tobias, J C Milisenda, J M Grau, F Crispi, E Gratacós, G Garrabou, F Cardellach
BACKGROUND: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication...
February 13, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29451807/coenzyme-q-10-from-bench-to-clinic-in-aging-diseases-a-translational-review
#3
Francisco M Gutierrez-Mariscal, Elena M Yubero-Serrano, Jose M Villalba, Jose Lopez-Miranda
Coenzyme Q 10 (CoQ 10 ) is a ubiquitous molecule present in all eukaryotic organisms whose principal role in the cell is related to its participation in the electron transport chain in the inner mitochondrial membrane. CoQ 10 plays a major role in the control of cell redox status, and both the amount and functionality of this molecule have been related to the regulation of reactive oxygen species generation. Numerous reports can be found discussing the implications of CoQ 10 supplementation in human studies and clinical trials related to aging...
February 16, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29450800/the-endogenous-subcellular-localisations-of-the-long-chain-fatty-acid-activating-enzymes-acsl3-and-acsl4-in-sarcoma-and-breast-cancer-cells
#4
Yassmeen Radif, Haarith Ndiaye, Vasiliki Kalantzi, Ruth Jacobs, Andrew Hall, Shane Minogue, Mark G Waugh
Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty acid activation is a critical step that allows these biomolecules to enter cellular metabolic pathways such as mitochondrial β-oxidation for ATP generation or the lipogenic routes that generate bioactive lipids such as the inositol phospholipids. Fatty acid activation by the addition of coenzyme A is catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL). Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a feature of some more aggressive cancers and may contribute to the oncogenic phenotype...
February 15, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29448286/-mitochondrial-dysfunctions-and-role-of-coenzyme-q10-in-patients-with-glaucoma
#5
Carl Erb, Katarzyna Konieczka
Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA)...
February 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29448137/differential-metabolism-of-l-phenylalanine-in-the-formation-of-aromatic-volatiles-in-melon-cucumis-melo-l-fruit
#6
Itay Gonda, Rachel Davidovich-Rikanati, Einat Bar, Shery Lev, Pliaa Jhirad, Yuval Meshulam, Guy Wissotsky, Vitaly Portnoy, Joseph Burger, Arthur A Schaffer, Yaakov Tadmor, James J Giovannoni, Zhangjun Fei, Aaron Fait, Nurit Katzir, Efraim Lewinsohn
Studies on the active pathways and the genes involved in the biosynthesis of L-phenylalanine-derived volatiles in fleshy fruits are sparse. Melon fruit rinds converted stable-isotope labeled L-phe into more than 20 volatiles. Phenylpropanes, phenylpropenes and benzenoids are apparently produced via the well-known phenylpropanoid pathway involving phenylalanine ammonia lyase (PAL) and being (E)-cinnamic acid a key intermediate. Phenethyl derivatives seemed to be derived from L-phe via a separate biosynthetic route not involving (E)-cinnamic acid and PAL...
February 12, 2018: Phytochemistry
https://www.readbyqxmd.com/read/29447225/low-apolipoprotein-a-i-levels-in-friedreich-s-ataxia-and-in-frataxin-deficient-cells-implications-for-therapy
#7
QingQing Wang, Lili Guo, Cassandra J Strawser, Lauren A Hauser, Wei-Ting Hwang, Nathaniel W Snyder, David R Lynch, Clementina Mesaros, Ian A Blair
Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder, which results primarily from reduced expression of the mitochondrial protein frataxin. FA has an estimated prevalence of one in 50,000 in the population, making it the most common hereditary ataxia. Paradoxically, mortality arises most frequently from cardiomyopathy and cardiac failure rather than from neurological effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of mortality from cardiomyopathy and heart failure...
2018: PloS One
https://www.readbyqxmd.com/read/29446872/does-selective-hormesis-impact-herbicide-resistance-evolution-in-weeds-accase-resistant-populations-of-alopecurus-myosuroides-huds-as-a-case-study
#8
Regina G Belz, Muhammad B Farooq, Jean Wagner
BACKGROUND: A field-evolved herbicide-resistant weed population can represent a heterogeneous composite of subpopulations that differ in their susceptibility and responsiveness to herbicide hormesis. Variable hormesis responsiveness can result in selection for and against certain subpopulations under low herbicide doses, and this has the potential to contribute to the evolution of resistance. The relevance of this hypothesis at practical field rates was studied for two field-collected acetyl-coenzyme A carboxylase (ACCase) target-site resistant (TSR) biotypes of Alopecurus myosuroides Huds...
February 15, 2018: Pest Management Science
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
#9
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/29445137/metabolic-features-of-cancer-stem-cells-the-emerging-role-of-lipid-metabolism
#10
REVIEW
Rita Mancini, Alessia Noto, Maria Elena Pisanu, Claudia De Vitis, Marcello Maugeri-Saccà, Gennaro Ciliberto
Cancer stem cells (CSCs) are an uncommon subset of tumor cells capable of self-renewal, differentiating, and recreating the parental tumor when transplanted into the murine background. Over the past two decades, efforts toward understanding CSC biology culminated into identifying a set of signaling pathways sustaining "stemness". Nevertheless, while metabolic rewiring is nowadays considered a hallmark of cancer, no consensus has been reached on the metabolic features underlying the plastic nature of CSCs, which are capable of residing in a dormant state, and able to rapidly proliferate when the need to repopulate the tumor mass arises...
February 15, 2018: Oncogene
https://www.readbyqxmd.com/read/29444838/enzyme-polymorphism-oxygen-and-injury-a-lipidomic-analysis-of-flight-induced-oxidative-damage-in-a-sdh-polymorphic-insect
#11
Julianne E Pekny, Philip B Smith, James H Marden
When active tissues receive insufficient oxygen to meet metabolic demand, succinate accumulates and has two fundamental effects: it causes ischemia-reperfusion injury while also activating the hypoxia-inducible factor pathway (HIF). The Glanville fritillary butterfly ( Melitaea cinxia ) possesses a balanced polymorphism in Sdhd, shown previously to affect HIF pathway activation and tracheal morphology and used here to experimentally test the hypothesis that variation in succinate dehydrogenase affects oxidative injury ...
February 14, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29441955/pegylation-of-coenzyme-q-10-and-in-vitro-release-studies
#12
M Zacchigna, F Cateni, G Procida, D Zampieri, M G Mamolo
Methoxy polyethylene glycol conjugated with coenzyme Q10 (mPEG)-CoQ10 and analog adducts with amino acids as spacers were synthesized as a new drug delivery systems for CoQ10. Alanine and branched chain amino acids (valine, leucine and isoleucine) were conjugated to mPEG by an amide linkage and to CoQ10 by an ester bond. Recently, branched chain amino acids (BCAAs), which are released along with CoQ10, have received increasing attention as 'anti-fatigue' elements. FT-IR and 1H NMR spectroscopic analysis were useful to characterize the synthesized conjugates...
December 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441875/influence-of-slco1b1-polymorphisms-on-atorvastatin-efficacy-and-safety-in-macedonian-subjects
#13
K Mladenovska, A Daka Grapci, M Vavlukis, A Kapedanovska, A Eftimov, N Matevska Geshkovska, D Nebija, A J Dimovski
Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin...
May 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29439058/autoimmune-necrotising-myopathy-and-hmgcr-antibodies
#14
Kushan Karunaratne, Dimitri Amiras, Matthew C Pickering, Monika Hofer, Stuart Viegas
Statins lower serum cholesterol concentrations by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle side effects are relatively common and include asymptomatic elevation of serum creatine kinase (CK), myalgia, proximal muscle weakness and rhabdomyolysis. More recently, a subset of cases of immune-mediated necrotising myopathy has been found to have antibodies against HMGCR. It is often an aggressive and debilitating myopathy and has a complex pathogenesis characterised by fibre necrosis, usually with minimal associated inflammation...
February 8, 2018: Practical Neurology
https://www.readbyqxmd.com/read/29435618/inactivation-of-an-intracellular-poly-3-hydroxybutyrate-depolymerase-of-azotobacter-vinelandii-allows-to-obtain-a-polymer-of-uniform-high-molecular-mass
#15
Libertad Adaya, Modesto Millán, Carlos Peña, Dieter Jendrossek, Guadalupe Espín, Raunel Tinoco-Valencia, Josefina Guzmán, Daniel Pfeiffer, Daniel Segura
A novel poly-3-hydroxybutyrate depolymerase was identified in Azotobacter vinelandii. This enzyme, now designated PhbZ1, is associated to the poly-3-hydroxybutyrate (PHB) granules and when expressed in Escherichia coli, it showed in vitro PHB depolymerizing activity on native or artificial PHB granules, but not on crystalline PHB. Native PHB (nPHB) granules isolated from a PhbZ1 mutant had a diminished endogenous in vitro hydrolysis of the polyester, when compared to the granules of the wild-type strain. This in vitro degradation was also tested in the presence of free coenzyme A...
February 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29434927/upregulation-of-pyruvate-kinase-m2-expression-by-fatty-acid-synthase-contributes-to-gemcitabine-resistance-in-pancreatic-cancer
#16
Shenghua Tian, Pingping Li, Shi Sheng, Xin Jin
Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resistance to gemcitabine, a chemotherapy treatment for pancreatic cancer; however, the mechanism by which this happens is unclear. Analysis of gene expression of FASN and pyruvate kinase M2 (PKM2) in pancreatic cancer was performed using Oncomine microarray gene expression datasets, which demonstrated that FASN and PKM2 were upregulated in pancreatic cancer compared with normal tissue...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434805/overexpression-of-heart-type-fatty-acid-binding-protein-enhances-fatty-acid-induced-podocyte-injury
#17
Qing Gao, Alhossain Sarkar, Yizhi Chen, Bo Xu, Xiaojuan Zhu, Yang Yuan, Tianjun Guan
Deregulated lipid metabolism is a characteristic of metabolic diseases including type 2 diabetes and obesity, and likely contributes to podocyte injury and end-stage kidney disease. Heart-type fatty acid binding protein (H-FABP) was reported to be associated with lipid metabolism. The present study investigated whether H-FABP contributes to podocyte homeostasis. Podocytes were transfected by lentiviral vector to construct a cell line which stably overexpressed H-FABP. Small interfering RNA capable of effectively silencing H-FABP was introduced into podocytes to construct a cell line with H-FABP knockdown...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29433856/studying-anti-oxidative-properties-of-inclusion-complexes-of-%C3%AE-lipoic-acid-with-%C3%AE-cyclodextrin-in-single-living-fission-yeast-by-confocal-raman-microspectroscopy
#18
Hemanth Noothalapati, Ryo Ikarashi, Keita Iwasaki, Tatsuro Nishida, Tomohiro Kaino, Keisuke Yoshikiyo, Keiji Terao, Daisuke Nakata, Naoko Ikuta, Masahiro Ando, Hiro-O Hamaguchi, Makoto Kawamukai, Tatsuyuki Yamamoto
α-lipoic acid (ALA) is an essential cofactor for many enzyme complexes in aerobic metabolism, especially in mitochondria of eukaryotic cells where respiration takes place. It also has excellent anti-oxidative properties. The acid has two stereo-isomers, R- and S- lipoic acid (R-LA and S-LA), but only the R-LA has biological significance and is exclusively produced in our body. A mutant strain of fission yeast, Δdps1, cannot synthesize coenzyme Q10, which is essential during yeast respiration, leading to oxidative stress...
February 6, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29432715/attenuation-of-cryopreservation-induced-oxidative-stress-by-antioxidant-impact-of-coenzyme-q10-on-the-quality-of-post-thawed-buck-spermatozoa
#19
Iman Yousefian, Mojtaba Emamverdi, Amir Karamzadeh-Dehaghani, Raziyeh Sabzian-Melei, Mahdi Zhandi, Ahmad Zare-Shahneh
The aim of this study was to determine the quality of post-thawed buck spermatozoa by attenuation of cryopreservation-induced oxidative stress using CoQ10, a lipophilic antioxidant. Ejaculates at every sampling period were collected from four Mahabadi bucks, pooled and diluted in soybean lecithin-based extenders containing 0 (negative control, NC), 0.5 (CQ0.05), 1 (CQ1), and 1.5 (CQ1.5) μM CoQ10 and 0.9% (v/v) DMSO (positive control, PC). The diluted semen was gradually cooled to 4 °C, then frozen and stored in liquid nitrogen...
February 9, 2018: Cryobiology
https://www.readbyqxmd.com/read/29430382/the-acyl-coa-binding-protein-affects-monascus-pigment-production-in-monascus-ruber-cicc41233
#20
Chuannan Long, Mengmeng Liu, Xia Chen, Xiaofang Wang, Mingqiang Ai, Jingjing Cui, Bin Zeng
The present study verified whether acyl-coenzyme A (acyl-CoA)-binding protein (ACBP) affected the production of Monascus pigments (MPs) in Monascus ruber CICC41233 (MrACBP). Phylogenetic analysis revealed that the cloned Mracbp gene, which encoded the MrACBP protein, exhibited the closest match (99% confidence level) to the gene from Penicilliopsis zonata . The MrACBP and maltose-binding protein (MBP) were simultaneously expressed in Escherichia coli Rosetta DE3 in the form of a fusion protein. The microscale thermophoresis binding assay revealed that the purified MBP-MrACBP exhibited a higher affinity for myristoyl-CoA (Kd = 88...
February 2018: 3 Biotech
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