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Annasofia Anemone, Lorena Consolino, Laura Conti, Francesca Reineri, Federica Cavallo, Silvio Aime, Dario Livio Longo
Dichloroacetate (DCA) can reverse the glycolytic phenotype that is responsible of increased lactate production and extracellular pH acidification in cancer cells. Magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) pH mapping is a novel non-invasive imaging approach that can measure in vivo extracellular tumour pH. We examined whether MRI-CEST pH mapping can monitor in vivo changes in tumour acidosis for assessing treatment response to DCA. Cell viability and extracellular pH were assessed in TS/A breast cancer cells treated with 1-10 mM DCA for 24 h in normoxia or hypoxia (1% O2) conditions...
August 2017: International Journal of Oncology
Yujiao Qin, Stephen J Gardner, Joshua Kim, Yimei Huang, Ning Wen, Anthony Doemer, Indrin J Chetty
PURPOSE: To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance (QA) measurements using flattening-filter-free beam. METHODS: A total of ten spherical targets (volume range: [0.03cc-2cc]) were planned with two techniques: (1) Dynamic Conformal Arc (DCA-10 plans), and (2) Volumetric Modulated Arc Therapy (VMAT-10 plans). All plans were generated using Varian Eclipse treatment planning system, and AcurosXB v...
July 17, 2017: Medical Physics
Weronika Kozanecka-Okupnik, Beata Jasiewicz, Tomasz Pospieszny, Monika Matuszak, Lucyna Mrówczyńska
Bile acids (lithocholic: LCA, deoxycholic: DCA and cholic: CA) and their formyl- and acetyl- derivatives can be used as starting material in chemical synthesis of compounds with different biological activity strongly depended on their chemical structures. Our previous studies showed that biological activity of bile acids salts with gramine toward human erythrocytes was significantly different from the activity of bile acids alone. Moreover, gramine effectively modified the membrane perturbing activity of other steroids...
July 12, 2017: Steroids
Qunyan Jin, Olivier Noel, Mai Nguyen, Lionel Sam, Glenn S Gerhard
Two major risk factors for ovarian cancer include loss-of-function mutations in the BRCA1 (breast cancer 1, early onset) gene and aspects of estrogen metabolism. Modulation of the levels of the normal BRCA1 allele and estrogen receptor expression may therefore be a preventive strategy. Consensus binding motifs for the bile acid-responsive transcription factor farnesoid X receptor were identified in the BRCA1 and estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes, supported by chromatin immunoprecipitation sequencing data...
July 12, 2017: European Journal of Cancer Prevention
Rizwan Ahmad, Bilal Rah, Dhundy Bastola, Punita Dhawan, Amar B Singh
Obesity increases susceptibility to multiple organ disorders, however, underlying mechanisms remain unclear. The subclinical inflammation assisted by obesity-induced gut permeability may underlie obesity-associated co-morbidities. Despite eminent clinical significance of the obesity led gut barrier abnormalities, its precise molecular regulation remains unclear. It is also unknown whether barrier deregulations, similar to the gut, characterize other vital organs in obese individuals. The claudin family of proteins is integral to the tight junction (TJ), the apical cell-cell adhesion and a key regulator of the epithelial barrier...
July 11, 2017: Scientific Reports
Tatsuya Higashi, Shui Watanabe, Koki Tomaru, Wataru Yamazaki, Kazumi Yoshizawa, Shoujiro Ogawa, Hidenori Nagao, Kouichi Minato, Masamitsu Maekawa, Nariyasu Mano
Although some studies have revealed the implication of bile acids (BAs) and neurological diseases, the levels and origin of the BAs in the brain are not fully understood. In this study, we first developed and validated a sensitive and specific method for the determination of three unconjugated BAs [cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)] in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry combined with chemical derivatization. The measured brain concentrations (mean ± standard deviation, n = 10) of normal rats were 58...
July 6, 2017: Steroids
Irina I Popadyuk, Andrey V Markov, Valeriya O Babich, Oksana V Salomatina, Evgeniya B Logashenko, Marina A Zenkova, Nariman F Salakhutdinov
A new library of deoxycholic acid derivatives bearing nitrogen-containing moieties at the C-3 position was synthesised from epoxy derivative 1 via an epoxide ring-opening reaction promoted by aliphatic or cyclic diamines and fully characterised by NMR and mass-spectroscopy. The synthesised compounds were screened for cytotoxicity against four human tumour cell lines. The results showed that some of the novel diamine-bearing derivatives displayed improved anti-proliferative activities over the parent compound DCA...
June 27, 2017: Bioorganic & Medicinal Chemistry Letters
Miu Iijima, Ryosuke Munakata, Hironobu Takahashi, Hiromichi Kenmoku, Ryuichi Nakagawa, Takeshi Kodama, Yoshinori Asakawa, Ikuro Abe, Kazufumi Yazaki, Fumiya Kurosaki, Futoshi Taura
Daurichromenic acid (DCA) synthase catalyzes the oxidative cyclization of grifolic acid to produce DCA, an anti-HIV meroterpenoid isolated from Rhododendron dauricum. We identified a novel cDNA encoding DCA synthase by transcriptome-based screening from young leaves of R. dauricum. The gene coded for a 533-amino acid polypeptide with moderate homologies to FAD oxidases from other plants. The primary structure contained an N-terminal signal peptide, and conserved amino acid residues to form bicovalent linkage to FAD isoalloxazine ring at His112 and Cys175...
July 5, 2017: Plant Physiology
Ling Li, Han Sun, Hiroaki Kitazawa, Xiangyou Wang
Browning is one of the main problems in senescence of mushrooms, and it is also one of the most important attributes accounting for the loss of the quality and reduction in market value. In order to study the relationship between the energy metabolism and the browning of white mushroom under high O2 dynamic-controlled atmosphere (HO-DCA), mushrooms were stored in 100% O2 (SCA1), 80% O2 + 20% CO2 (SCA2), 100% O2 for three days and then transferred into the treatment of 80% O2 + 20% CO2 (HO-DCA) at 2 ± 1 ℃ and air as control...
July 2017: Food Science and Technology International, Ciencia y Tecnología de Los Alimentos Internacional
Elin Birgersson, Jochen M Schwenk, Burcu Ayoglu
Antibody microarrays offer high-throughput immunoassays for multiplexed analyses of clinical samples. For such approaches, samples are either labeled in solution to enable a direct readout on the single binder assay format or detected by matched pairs of capture and detection antibodies in dual binder assay format, also known as sandwich assays. Aiming to benefit from the flexibility and capacity offered by single binder assay readout and the specificity and sensitivity of dual binder assays, we developed a multiplexed dual binder procedure that is based on a sequential, rather than combined, antigen binding...
2017: Methods in Molecular Biology
Ximing Xu, Cecile Mathieu, Jeremy Berthelet, Romain Duval, Linh Chi Bui, Florent Busi, Jean-Marie Dupret, Fernando Rodrigues-Lima
Thiram (tetramethylthiuram disulfide) is a representative dithiocarbamate (DTC) pesticide used in both the field and as a seed protectant. The widespread use of Thiram and other DTC pesticides has raised concerns for health as these compounds can exert neuropathic, endocrine disruptive and carcinogenic effects. These toxic effects are thought to rely, at least in part, on the reaction of Thiram (and certain of its metabolites) with cellular protein thiols with subsequent loss of protein function. So far, a limited number of molecular targets of Thiram have been reported including few enzymes such as dopamine β-hydroxylase, 11β-hydroxysteroid dehydrogenase and brain glycogen phosphorylase...
July 3, 2017: Molecular Pharmacology
Rong Jin, Xuelian Guo, Lingli Dong, Enyuan Xie, Aoneng Cao
A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH2) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH2. These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX...
June 21, 2017: Colloids and Surfaces. B, Biointerfaces
Vedagopuram Sreekanth, Nihal Medatwal, Sanjay Pal, Sandeep Kumar, Sagar Sengupta, Avinash Bajaj
Lipid composition in general determines the drug encapsulation efficacy and release kinetics from liposomes that impact the clinical outcomes of cancer therapy. We synthesized three bile acid phospholipids by conjugating the phosphocholine head group to the 3'-hydroxyl group of benzylated lithocholic acid (LCA), deoxycholic acid (DCA), and cholic acid (CA); and investigated the impact of membrane rigidity on drug encapsulation efficacy, drug release kinetics, anticancer effects, and mice survival. Liposomes with hydrodynamic diameter of 100-110 nm were subsequently developed using these phospholipids...
June 30, 2017: Molecular Pharmaceutics
Marco Fantini, Duccio Malinverni, Paolo De Los Rios, Annalisa Pastore
Direct coupling analysis (DCA) is a powerful statistical inference tool used to study protein evolution. It was introduced to predict protein folds and protein-protein interactions, and has also been applied to the prediction of entire interactomes. Here, we have used it to analyze three proteins of the iron-sulfur biogenesis machine, an essential metabolic pathway conserved in all organisms. We show that DCA can correctly reproduce structural features of the CyaY/frataxin family (a protein involved in the human disease Friedreich's ataxia) despite being based on the relatively small number of sequences allowed by its genomic distribution...
2017: Frontiers in Molecular Biosciences
Scott O C Mundle, Jim C Spain, Georges Lacrampe-Couloume, Shirley F Nishino, Barbara Sherwood Lollar
Compound specific isotope analysis (CSIA) is widely used to monitor contaminant remediation in groundwater. CSIA-based approaches that use enrichment (ε) values to assess degradative processes rely on the assumption that the contaminant being investigated will have an ε value that is constant and specific to a catalytic pathway of a microorganism. Distinct ε values have been reported for aerobic degradation of cis-dichloroethene (cDCE), which has led to a number of proposed degradation mechanisms; however, cytochrome P450 catalyzed oxidation is the only biochemical mechanism that has been established in Polaromonas sp...
June 26, 2017: Science of the Total Environment
Bo Li, Xinzhe Li, Haojun Xiong, Peng Zhou, Zhenhong Ni, Teng Yang, Yan Zhang, Yijun Zeng, Jintao He, Fan Yang, Nan Zhang, Yuting Wang, Yingru Zheng, Fengtian He
Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells...
June 16, 2017: Oncotarget
Su Chen, Ekaterina I Izgorodina
Nuclear magnetic resonance (NMR) has been widely used to elucidate the bulk structure of ionic liquids. In this work, we calculated (1)H NMR chemical shifts of 1-ethyl-3-methylimidazolium (C2mim(+)) ionic liquids combined with various anions such as chloride (Cl), tetrafluoroborate (BF4), hexafluorophosphate (PF6), acetate (OAc), trifluoroacetate (TFA), and dicyanamide (DCA). The previously established level of theory, HF/6-311G+(3df,2p), was used for the accurate prediction of NMR chemical shifts both in gas phase and in solvents with varying dielectric constant such as CHCl3 and ethanol...
June 26, 2017: Physical Chemistry Chemical Physics: PCCP
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
Sam C Barnes, Naomi Ball, Victoria Joanna Haunton, Ronney B Panerai, Thompson G Robinson
BACKGROUND: Squat-stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed-frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA, and to determine the reproducibility of FF and RFSSMs. METHOD: 29 healthy volunteers (19 male, mean age 23.0 [4.9] years) completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2 and angle of the squat movement were measured...
June 22, 2017: Journal of Applied Physiology
Paola Romecín, Esther G Navarro, M Clara Ortiz, David Iyú, Joaquín García-Estañ, Noemí M Atucha
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model...
2017: Frontiers in Physiology
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