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https://www.readbyqxmd.com/read/28732368/meta-analysis-of-micrornas-expression-in-head-and-neck-cancer-uncovering-association-with-outcome-and-mechanisms
#1
Joshua Lubov, Mariana Maschietto, Iman Ibrahim, Alex Mlynarek, Michael Hier, Luiz Paulo Kowalski, Moulay A Alaoui-Jamali, Sabrina Daniela da Silva
Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732133/ionization-and-collision-induced-dissociation-of-steroid-bis-glucuronides
#2
Argitxu Esquivel, Xavier Matabosch, Aristotelis Kotronoulas, Georgina Balcells, Jesús Joglar, Rosa Ventura
Studies on steroid metabolism are of utmost importance to improve the detection capabilities of anabolic androgenic steroids (AAS) misuse in sports drug testing. In humans, glucuronoconjugates are the most abundant phase II metabolites of AAS. Bis-glucuronidation is a reaction where two separated functional groups on the same molecule are conjugated with glucuronic acid. These metabolites have not been studied in depth for steroids and could be interesting markers for doping control. The aim of the present work was to study the ionization and collision induced dissociation of steroid bis-glucuronides to be able to develop mass spectrometric analytical strategies for their detection in urine samples after AAS administration...
July 21, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#3
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28731668/-azathioprine-induced-pancytopenia-case-series
#4
Cristina Martínez Faci, Ignacio Ros Arnal, José M Martínez de Zabarte Fernández, Jordi Sorribes Estorch, Mónica López Campos, Carmen Rodríguez-Vigil Iturrate
Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts...
August 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28731364/synthesis-of-a-new-insulin-mimetic-anti-diabetic-drug-containing-vitamin-a-and-vanadium-iv-salt-chemico-biological-characterizations
#5
Abdel Majid A Adam, Ahmed M Naglah, Mohamed A Al-Omar, Moamen S Refat
Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its -OH group...
July 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28731323/analyzing-liposomal-drug-delivery-systems-in-three-dimensional-cell-culture-models-using-maldi-imaging-mass-spectrometry
#6
Jessica K Lukowski, Eric M Weaver, Amanda B Hummon
Cancer chemotherapeutics often fail to reach all diseased cells. To help solve this problem, researchers are investigating novel drug delivery systems. Liposomes are an attractive option due to their low toxicity, high biocompatibility, and potential to carry a large amount of a drug to the tumor site, all while avoiding being eliminated from the body. This study evaluates the penetration of doxorubicin-encased liposomes into three-dimensional cell cultures, or spheroids. Liposomes composed of lipids containing head groups of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cholesterol were created by extrusion...
July 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28731321/conjugation-dependent-interaction-of-folic-acid-with-folate-binding-protein
#7
Rachel Leah Merzel, Carolina Frey, Junjie Chen, Rachel Garn, Mallory A van Dongen, Casey A Dougherty, Ananda Kandaluru, Philip S Low, E Neil G Marsh, Mark M Banaszak Holl
Serum proteins play a critical role in the transport, uptake, and efficacy of targeted drug therapies, and here we investigate the interactions between folic acid-polymer conjugates and serum folate binding protein (FBP), the soluble form of the cellular membrane-bound folate receptor. We demonstrate that both choice of polymer and method of ligand conjugation affect the interactions between folic acid-polymer conjugates and serum FBP, resulting in changes in the folic acid-induced protein aggregation process...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731312/gentiana-kurroo-royle-attenuates-the-metabolic-aberrations-in-diabetic-rats-swertiamarin-swertisin-and-lupeol-being-the-possible-bioactive-principles
#8
Khalid Ghazanfar, Khan Mubashir, Showkat A Dar, Tazeen Nazir, Iqra Hameed, Bashir A Ganai, Seema Akbar, Akbar Masood
Background Gentiana kuroo Royle is a medicinally important plant of north-western Himalayas used for various ailments. In the present study, the plant extracts were investigated for the antidiabetic effects in streptozotocin-induced diabetic rats. Methods The impact of the extracts on serum glucose levels of diabetic rats was compared with reference drug - glibenclamide-treated diabetic rats. Streptozotocin injection was used to induce diabetes in fasted rats. Various biochemical, physiological and histopathological parameters in diabetic rats were observed for assessing the antidiabetic activity...
April 29, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28731281/glycaemic-control-and-the-risk-of-hospitalisation-for-infection-in-patients-with-type-2-diabetes-hong-kong-diabetes-registry
#9
Andrea O Y Luk, Eric S H Lau, Kitty K T Cheung, Alice P Kong, Ronald C W Ma, Risa Ozaki, Francis C C Chow, Wing-Yee So, Juliana C N Chan
BACKGROUND: Infection occurs more commonly in diabetic compared to general population and is an under-recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes. METHODS: Between July 1994 and June 2014, 22,846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications...
July 21, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28730824/glucagon-like-peptide-1-analogues-exenatide-and-liraglutide-exert-inhibitory-effect-on-the-early-phase-of-liver-regeneration-after-partial-hepatectomy-in-rats
#10
J Fontana, O Kučera, V Mezera, M Anděl, Z Červinková
Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730493/magnetic-resonance-spectroscopy-mrs-based-methods-for-examining-cancer-metabolism-in-response-to-oncogenic-kinase-drug-treatment
#11
Yuen-Li Chung
Magnetic resonance spectroscopy (MRS) is an analytical technique that has been extensively used to examine reprogrammed metabolism and treatment response in cancer cells and solid tumors both in vivo and ex vivo. High-resolution MRS (HR-MRS) is one of the best methods for metabolic profiling, as it is highly quantitative, robust, and reproducible. The protocols for dual-phase extraction of cancer cells and tumors and sample preparations for high-resolution (1)H and (31)P HR-MRS analysis are described here. Descriptions of spectra acquisition and analysis are also included in this chapter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730152/zebrafish-get-connected-investigating-neurotransmission-targets-and-alterations-in-chemical-toxicity
#12
Katharine A Horzmann, Jennifer L Freeman
Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined...
September 2016: Toxics
https://www.readbyqxmd.com/read/28729963/advances-in-applications-of-metabolomics-in-pluripotent-stem-cell-research
#13
Vijesh J Bhute, Xiaoping Bao, Sean P Palecek
Stem cells undergo extensive metabolic rewiring during reprogramming, proliferation and differentiation, and numerous studies have demonstrated a significant role of metabolism in controlling stem cell fates. Recent applications of metabolomics, the study of concentrations and fluxes of small molecules in cells, have advanced efforts to characterize and maturate stem cell fates, assess drug toxicity in stem cell tissue models, identify biomarkers, and study the effects of environment on metabolic pathways in stem cells and their progeny...
February 2017: Current Opinion in Chemical Engineering
https://www.readbyqxmd.com/read/28729164/antenatal-antipsychotic-exposure-induces-multigenerational-and-gender-specific-programming-of-adiposity-and-glucose-tolerance-in-adult-mouse-offspring
#14
E Courty, P Gobalakichenane, M Garcia, A Muscat, C Kazakian, T Ledent, M Moldes, B Blondeau, D Mitanchez, M Buyse, B Fève
Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring...
July 17, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28729056/discovery-and-structure-activity-relationship-of-auriculatone-a-potent-hepatoprotective-agent-against-acetaminophen-induced-liver-injury
#15
Meng Zhou, Min Wang, Rui-Feng Zhong, Xiang-Ming Liao, Lian-Li Deng, Guo-Bo Xu, Xun He, Jing Li, Yong-Jun Li, Ting Liu, Yong-Lin Wang, Shang-Gao Liao
Acetaminophen (APAP, paracetamol) overdose has been the most frequent cause of drug-induced liver failure. APAP-induced liver toxicity can be fatal in many cases even with treatment of the clinically used N-acetylcysteine (NAC), and the need for novel therapeutic agents is apparent. Through evaluating the hepatoprotective effects of the co-occurring substances present in oleanolic acid tablets which have been used in China for decades as an adjuvant therapy for acute and chronic hepatitis, auriculatone was found to protect HL-7702 cells from APAP-induced liver injury comparable to NAC at the concentration of 10μM...
July 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28729055/novel-1-2-dihydroquinazolin-2-ones-design-synthesis-and-biological-evaluation-against-trypanosoma-brucei
#16
ThanhTruc Pham, Madeline Walden, Christopher Butler, Rosario Diaz-Gonzalez, Guiomar Pérez-Moreno, Gloria Ceballos-Pérez, Veronica Gomez-Pérez, Raquel García-Hernández, Henry Zecca, Emma Krakoff, Brian Kopec, Ogar Ichire, Caden Mackenzie, Marika Pitot, Luis Miguel Ruiz, Francisco Gamarro, Dolores González-Pacanowska, Miguel Navarro, Amy B Dounay
In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability...
July 11, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28729031/knockout-of-the-urate-oxidase-gene-provides-a-stable-mouse-model-of-hyperuricemia-associated-with-metabolic-disorders
#17
Jie Lu, Xu Hou, Xuan Yuan, Lingling Cui, Zhen Liu, Xinde Li, Lidan Ma, Xiaoyu Cheng, Ying Xin, Can Wang, Keke Zhang, Xuefeng Wang, Wei Ren, Ruixia Sun, Zhaotong Jia, Zibin Tian, Qing-Sheng Mi, Changgui Li
The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28728997/sepsis-reconsidered-identifying-novel-metrics-for-behavioral-landscape-characterization-with-a-high-performance-computing-implementation-of-an-agent-based-model
#18
Chase Cockrell, Gary An
OBJECTIVES: Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models...
July 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28728153/genetic-variants-of-cytochrome-cyp2d6-in-two-mixed-chilean-populations
#19
Mónica Acuña, Eric Pinto, Paulina Olivares, Carolina Ríos
OBJECTIVES: It is known that the interindividual and interethnic variability of the genetic polymorphisms of CYP2D6 plays an important role in the presentation of adverse drug reactions and concerning lack of therapeutic effects in humans. However, there are few data available from mixed populations of Latin America, including the Chilean. The aim of this study was therefore to estimate the frequencies of CYP2D6 variants in two samples of hospitals from the northern (Hospital San José, HSJ) and eastern (Clínica Las Condes, CLC) parts of Santiago, Chile, with different degrees of Amerindian admixture (HSJ: 34...
July 21, 2017: Human Heredity
https://www.readbyqxmd.com/read/28728150/fisher-discrimination-of-metabolic-changes-in-rats-treated-with-aspirin-and-ibuprofen
#20
Jing Zhang, Huanchun Song, Shuying Jiang, Zhibin Chen, Shuhua Tong, Feiyan Lin, Congcong Wen, Xiuhua Zhang, Lufeng Hu
BACKGROUND: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. METHODS: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks...
July 21, 2017: Pharmacology
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