This model was found in 397 unique locations in 35 countries, where it was mentioned from 1999 until recently.
Questpair Analytics found the Applied Biosystems 4000 at 397 research organisations and laboratories in 35 countries, in publications from 1999 until recently. It is used most in Biochemistry, Molecular Biology and Pharmacology.
Usage over time
Mentions peaked in 2010.
Research fields
The Applied Biosystems 4000 is used by scientists in research fields such as Biochemistry, Molecular Biology, Pharmacology, General Medicine and Molecular Medicine.
The model was found at 397 locations in 35 countries.
| Organisation | Instrument | City | Country |
|---|---|---|---|
Tohoku University | Applied Biosystems 4000 QTRAP | Sendai | Japan |
University of Minnesota | Applied Biosystems 4000 QTRAP | Minneapolis | United States |
Western University | Applied Biosystems 4000 QTRAP | London | Canada |
Akdeniz University | Applied Biosystems 4000 QTRAP | Antalya | Turkey |
University of Adelaide | Applied Biosystems 4000 QTRAP | Adelaide | Australia |
Stony Brook University | Applied Biosystems 4000 QTRAP | Princeton | United States |
Only abstracts that are published under Creative Commons Attribution 4.0 are shown on this page.
CMTR1 contributes to mRNA cap formation by methylating the first transcribed nucleotide ribose at the O-2 position. mRNA cap O-2 methylation has roles in mRNA stabilisation and translation, and self-RNA tolerance in innate immunity. We report that CMTR1 is recruited to serine-5–phosphorylated RNA Pol II C-terminal domain, early in transcription. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1. When DHX15 is bound, CMTR1 activity is repressed and the methyltransferase does not bind to RNA pol II. Conversely, CMTR1 activates DHX15 helicase activity, which is likely to impact several nuclear functions. In HCC1806 breast carcinoma cell line, the DHX15–CMTR1 interaction controls ribosome loading of a subset of mRNAs and regulates cell proliferation. The impact of the CMTR1–DHX15 interaction is complex and will depend on the relative expression of these enzymes and their interactors, and the cellular dependency on different RNA processing pathways.
Francisco Inesta-Vaquera, Viduth K Chaugule, Alison Galloway, Laurel Chandler, Alejandro Rojas-Fernandez, Simone Weidlich, Mark Peggie, Victoria H Cowling. Life Science Alliance, 1 (3), e201800092, 2018.
Read the publicationBackground: While oxylipins have been linked to coronary artery disease (CAD), little is known about their diagnostic and prognostic potential.
Objective: We tested whether plasma concentration of specific oxylipins may discriminate among number of diseased coronary arteries and predict median 5-year outcomes in symptomatic adults.
Methods: Using a combination of high-performance liquid chromatography (HPLC) and quantitative tandem mass spectrometry, we conducted a targeted analysis of 39 oxylipins in plasma samples of 23 asymptomatic adults with low CAD risk and 74 symptomatic adults (≥70% stenosis), aged 38–87 from the Greater Portland, Oregon area. Concentrations of 22 oxylipins were above the lower limit of quantification in >98% of adults and were compared, individually and in groups based on precursors and biosynthetic pathways, in symptomatic adults to number of diseased coronary arteries [(1) n = 31; (2) n = 23; (3) n = 20], and outcomes during a median 5-year follow-up (no surgery: n = 7; coronary stent placement: n = 24; coronary artery bypass graft surgery: n = 26; death: n = 7).
Results: Plasma levels of six quantified oxylipins decreased with the number of diseased arteries; a panel of five oxylipins diagnosed three diseased arteries with 100% sensitivity and 70% specificity. Concentrations of five oxylipins were lower and one oxylipin was higher with survival; a panel of two oxylipins predicted survival during follow-up with 86% sensitivity and 91% specificity.
Conclusions: Quantification of plasma oxylipins may assist in CAD diagnosis and prognosis in combination with standard risk assessment tools.
D. Elizabeth Le, Manuel García-Jaramillo, Gerd Bobe, Armando Alcazar Magana, Ashish Vaswani, Jessica Minnier, Donald B. Jump, Diana Rinkevich, Nabil J. Alkayed, Claudia S. Maier, Sanjiv Kaul. Frontiers in Cardiovascular Medicine, 8, 2021.
Read the publicationPhosphorus (P) deficiency is one of the major limiting factors for crop productivity. The yield of rice (Oryza sativa L.) is severely limited by phosphorus deficiency. An attempt has been made in this study to identify P deficiency responsive differentially expressed proteins of rice through analysis of leaf proteome of contrasting P-responsive rice cultivars under P deficiency conditions because genetic variability has been found in the rice cultivars for adaptive response to P deficiency and a controlled regulatory system is involved in the P deficiency adaptation response. Phosphorus-efficient (cv. Panvel) and P-inefficient (cv. Nagina 22) rice cultivars were hydroponically grown in the nutrient medium under control environmental conditions at low-P level (2.0 µM) and optimum-P level (320 µM) treatments. Expression patterns of the proteins of the leaves of both the cultivars were analyzed in 30-day-old plants. The identification of these proteins through mass spectrometry and MASCOT software (Matrix Science Inc., Boston, USA) revealed that these differentially expressed proteins were homologous to known functional proteins involved in energy metabolism, biosynthesis, photosynthesis, signaling, protein synthesis, protein folding, phospholipid metabolism, oxidative stress, transcription factors, and phosphorus metabolism. It has been observed that rice cultivars responded differently to low-P treatment through modification in protein expressions pattern to maintain the growth of the plants. Therefore, the expression patterns of proteins were different in both of the cultivars under low-P treatment. Higher potential of protein stability, stress tolerance, osmo-protection, and regulation of phosphorus uptake was observed in cv. Panvel than cv. Nagina 22. This study could help to unravel the complex regulatory process that is involved in adaptation to P deficiency in rice.
Aadil Yousuf Tantray, Hayssam M. Ali, Altaf Ahmad. Agronomy, 10 (7), 1028, 2020.
Read the publicationTraditionally, Agastache rugosa (Korean mint) has been widely used to treat various infectious diseases. The aims of this study were to: (i) determine the phenylpropanoid content of the plant using high-performance liquid chromatography; (ii) undertake total anthocyanin, flavonoid, and phenolic assays; (iii) and evaluate the antioxidant and antibacterial properties of the methanol extracts from the stem, leaves, and flowers of Korean mint. The total anthocyanin, flavonoid, and phenolic content assays showed that the flowers had higher phenolic levels than the stem and leaves. The reducing power, the 2,2-diphenyl-1-picrylhydrazyl superoxide radical scavenging abilities, and the hydrogen peroxide radical scavenging activities were also evaluated so that the antioxidant activities of the extracts from the different plant parts could be evaluated. The flower extracts revealed higher antioxidant properties than the other parts. The antibacterial properties of the methanol extracts from A. rugosa were analyzed by the disc diffusion method, and the flower extracts had higher antibacterial activities against the six bacterial strains used in the study than the other parts. This study provides information on the synergistic antioxidant and antibacterial properties of phenolics derived from the different parts of Korean mint.
Chang Park, Hyeon Yeo, Thanislas Baskar, Ye Park, Jong Park, Sook Lee, Sang Park. Antioxidants, 8 (3), 75, 2019.
Read the publicationAt present, there are still numerous unresolved questions concerning the mechanisms of light-absorbing organic aerosol (brown carbon, BrC) formation in the atmosphere. Moreover, there is growing evidence that chemical processes in the atmospheric aqueous phase can be important. In this work, we investigate the aqueous-phase formation of BrC from 3-methylcatechol (3MC) under simulated sunlight conditions. The influence of different HNO2/NO2− concentrations on the kinetics of 3MC degradation and BrC formation was investigated. Under illumination, the degradation of 3MC is faster (k2nd(global) = 0.075 M−1·s−1) in comparison to its degradation in the dark under the same solution conditions (k2nd = 0.032 M−1·s−1). On the other hand, the yield of the main two products of the dark reaction (3-methyl-5-nitrocatechol, 3M5NC, and 3-methyl-4-nitrocatechol, 3M4NC) is low, suggesting different degradation pathways of 3MC in the sunlight. Besides the known primary reaction products with distinct absorption at 350 nm, second-generation products responsible for the absorption above 400 nm (e.g., hydroxy-3-methyl-5-nitrocatechol, 3M5NC-OH, and the oxidative cleavage products of 3M4NC) were also confirmed in the reaction mixture. The characteristic mass absorption coefficient (MAC) values were found to increase with the increase of NO2−/3MC concentration ratio (at the concentration ratio of 50, MAC is greater than 4 m2·g−1 at 350 nm) and decrease with the increasing wavelength, which is characteristic for BrC. Yet, in the dark, roughly 50% more BrC is produced at comparable solution conditions (in terms of MAC values). Our findings reveal that the aqueous-phase processing of 3MC in the presence of HNO2/NO2−, both under the sunlight and in the dark, may significantly contribute to secondary organic aerosol (SOA) light absorption.
Kristijan Vidović, Ana Kroflič, Martin Šala, Irena Grgić. Atmosphere, 11 (2), 131, 2020.
Read the publicationBackground: Lung cancer is the most common cause of cancer-related deaths worldwide. Early diagnosis is crucial to increase the curability chance of the patients. Low dose CT screening can reduce lung cancer mortality, but it is associated with several limitations. Metabolomics is a promising technique for cancer diagnosis due to its ability to provide chemical phenotyping data. The intent of our study was to explore metabolomic effects and profiles of lung cancer patients to determine if metabolic perturbations in the SSAT-1/polyamine pathway can distinguish between healthy participants and lung cancer patients as a diagnostic and treatment monitoring tool. Patients and Methods: Plasma samples were collected as part of the SSAT1 Amantadine Cancer Study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and quantify metabolite concentrations in lung cancer patient and control samples. Standard statistical analyses were performed to determine whether metabolite concentrations could differentiate between healthy subjects and lung cancer patients, as well as risk prediction modeling applied to determine whether metabolic profiles could provide an indication of cancer progression in later stage patients. Results: A panel consisting of 14 metabolites, which included 6 metabolites in the polyamine pathway, was identified that correctly discriminated lung cancer patients from controls with an area under the curve of 0.97 (95% CI: 0.875-1.0). Conclusion: When used in conjunction with the SSAT-1/polyamine pathway, these metabolites may provide the specificity required for diagnosing lung cancer from other cancer types and could be used as a diagnostic and treatment monitoring tool.
Sandeep Singhal, Christian Rolfo, Andrew W. Maksymiuk, Paramjit S. Tappia, Daniel S. Sitar, Alessandro Russo, Parveen S. Akhtar, Nazrina Khatun, Parveen Rahnuma, Ahmed Rashiduzzaman, Rashid Ahmed Bux, Guoyu Huang, Bram Ramjiawan. Cancers, 11 (8), 1069, 2019.
Read the publicationMultiple myeloma (MM) is well-known for the development of drug resistance, leading to relapse. Therefore, finding novel treatment strategies remains necessary. By performing a lipidomics assay on MM patient plasma, we aimed to identify new targets. We observed a dysregulation in the sphingolipid metabolism, with the upregulation of several ceramides and downregulation of sphingomyelin. This imbalance suggests an increase in sphingomyelinase, the enzyme responsible for hydrolyzing sphingomyelin into ceramide. We confirmed the upregulation of acid sphingomyelinase (ASM) in primary MM cells. Furthermore, we observed an increase in ASM expression in MM cell lines treated with melphalan or bortezomib, as well as in their exosomes. Exosomes high in ASM content were able to transfer the drug-resistant phenotype to chemosensitive cells, hereby suggesting a tumor-protective role for ASM. Finally, inhibition of ASM by amitriptyline improved drug sensitivity in MM cell lines and primary MM cells. In summary, this study is the first to analyze differences in plasma lipid composition of MM patients and match the observed differences to an upregulation of ASM. Moreover, we demonstrate that amitriptyline is able to inhibit ASM and increase sensitivity to anti-myeloma drugs. This study, therefore, provides a rational to include ASM-targeting-drugs in combination strategies in myeloma patients.
Sylvia Faict, Inge Oudaert, Ludovic D’Auria, Jonas Dehairs, Ken Maes, Philip Vlummens, Kim De Veirman, Elke De Bruyne, Karel Fostier, Isabelle Vande Broek, Rik Schots, Karin Vanderkerken, Johannes V. Swinnen, Eline Menu. Cancers, 11 (12), 1823, 2019.
Read the publicationThe objective of this research is to use metabolomic techniques to discover and validate plasma metabolite biomarkers for the diagnosis of early-stage non-small cell lung cancer (NSCLC). The study included plasma samples from 156 patients with biopsy-confirmed NSCLC along with age and gender-matched plasma samples from 60 healthy controls. A fully quantitative targeted mass spectrometry (MS) analysis (targeting 138 metabolites) was performed on all samples. The sample set was split into a discovery set and validation set. Metabolite concentration data, clinical data, and smoking history were used to determine optimal sets of biomarkers and optimal regression models for identifying different stages of NSCLC using the discovery sets. The same biomarkers and regression models were used and assessed on the validation models. Univariate and multivariate statistical analysis identified β-hydroxybutyric acid, LysoPC 20:3, PC ae C40:6, citric acid, and fumaric acid as being significantly different between healthy controls and stage I/II NSCLC. Robust predictive models with areas under the curve (AUC) > 0.9 were developed and validated using these metabolites and other, easily measured clinical data for detecting different stages of NSCLC. This study successfully identified and validated a simple, high-performing, metabolite-based test for detecting early stage (I/II) NSCLC patients in plasma. While promising, further validation on larger and more diverse cohorts is still required.
Lun Zhang, Jiamin Zheng, Rashid Ahmed, Guoyu Huang, Jennifer Reid, Rupasri Mandal, Andrew Maksymuik, Daniel S. Sitar, Paramjit S. Tappia, Bram Ramjiawan, Philippe Joubert, Alessandro Russo, Christian D. Rolfo, David S. Wishart. Cancers, 12 (3), 622, 2020.
Read the publicationA feeding experiment was carried out with late-lactating cows over 12 weeks to evaluate the feeding value of a basic diet with maize and grass silage (MS, GS) when combined with varying portions of concentrate in the ration (20% and 60% on a dry matter basis) and to test the effects on health and performance, the transfer of important Fusarium toxins to blood and milk, the total and Shiga toxin (stx)-forming E. coli counts, and the presence of Clostridium botulinum neurotoxin (BoNT) genes in rectal fecal samples. MS was contaminated by a broader spectrum of fungal and other metabolites compared to GS. MS contained higher concentrations of the important Fusarium toxins deoxynivalenol (DON) and zearalenone (ZEN). Blood and milk levels of DON and ZEN residues generally reflected the differences in exposure at a low level. Feeding of MS with 60% concentrate feed induced subacute ruminal acidosis (SARA) associated with a marked drop in dry matter intake, fat corrected milk yield and a fat to protein ratio in milk of lower than 1. The SARA-associated higher ruminal LPS concentration did not affect the circulating concentrations of haptoglobin as an indicator of systemic inflammation. Lower rumen pH values in both MS-fed groups were associated with lower pH values, higher absolute E. coli counts and increased proportions of stx-positive E. coli in rectal feces. BoNT genes A, B, C, D, E and F remained undetectable in any of the fecal samples suggesting that feedstuffs were virtually free of the corresponding C. botulinum strains. In conclusion, maize feedstuff (silage, grains, starch-containing byproducts)-dominated rations for dairy cows should be avoided to reduce adverse effects on health and food safety.
Sven Dänicke, Julia Krenz, Christian Seyboldt, Heinrich Neubauer, Jana Frahm, Susanne Kersten, Karsten Meyer, Janine Saltzmann, Wolfram Richardt, Gerhard Breves, Helga Sauerwein, Michael Sulyok, Ulrich Meyer, Lutz Geue. Dairy, 1 (2), 91-125, 2020.
Read the publicationThe angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.
Karis Ederer, Kelly Jin, Sarah Bouslog, Lu Wang, Gregory Gorman, Glenn Rowe, Peter Abadir, Daniel Raftery, Douglas Moellering, Daniel Promislow, Patricia Jumbo-Lucioni, Maria De Luca. International Journal of Molecular Sciences, 19 (11), 3351, 2018.
Read the publicationSmut disease is caused by Sporisorium scitamineum, an important sugarcane fungal pathogen causing an extensive loss in yield and sugar quality. The available literature suggests that there are two types of smut resistance mechanisms: external resistance by physical or chemical barriers and intrinsic internal resistance mechanisms operating at host–pathogen interaction at cellular and molecular levels. The nature of smut resistance mechanisms, however, remains largely unknown. The present study investigated the changes in proteome occurring in two sugarcane varieties with contrasting susceptibility to smut—F134 and NCo310—at whip development stage after S. scitamineum infection. Total proteins from pathogen inoculated and uninoculated (control) leaves were separated by two-dimensional gel electrophoresis (2D-PAGE). Protein identification was performed using BLASTp and tBLASTn against NCBI nonredundant protein databases and EST databases, respectively. A total of thirty proteins spots representing differentially expressed proteins (DEPs), 16 from F134 and 14 from NCo310, were identified and analyzed by MALDI-TOF/TOF MS. In F134, 4 DEPs were upregulated and nine were downregulated, while, nine were upregulated and three were downregulated in NCo310. The DEPs were associated with DNA binding, metabolic processes, defense, stress response, photorespiration, protein refolding, chloroplast, nucleus and plasma membrane. Finally, the expression of CAT, SOD, and PAL with recognized roles in S. scitamineum infection in both sugarcane verities were analyzed by real-time quantitative PCR (RT-qPCR) technique. Identification of genes critical for smut resistance in sugarcane will increase our knowledge of S. scitamineum-sugarcane interaction and help to develop molecular and conventional breeding strategies for variety improvement.
Pratiksha Singh, Qi-Qi Song, Rajesh Singh, Hai-Bi Li, Manoj Solanki, Mukesh Malviya, Krishan Verma, Li-Tao Yang, Yang-Rui Li. International Journal of Molecular Sciences, 20 (3), 569, 2019.
Read the publicationMaize ZmC1 and ZmR transcription factors belong to the MYB-type and bHLH families, respectively, and control anthocyanin biosynthesis. In this study, Agrobacterium-mediated transformation was used to generate transgenic wheat plants that overexpress ZmC1 and ZmR or both, with the objective of developing anthocyanin-enriched wheat germplasm. Three kinds of stable transgenic wheat lines were obtained. The integration of target genes in the transgenic wheat plants was confirmed by fluorescence in situ hybridization (FISH) analysis. We found that single overexpression of ZmC1 regulates pigmentation in the vegetative tissues such as coleoptiles, auricles, and stems. The single overexpression of ZmR controls the coloration in reproductive tissue like spikelets and seeds. The simultaneous overexpression of ZmC1 and ZmR showed the strongest pigmentation in almost all tissues. Furthermore, quantitative real-time PCR (qRT-PCR) analysis revealed that expression of the two transgenes, and of two conserved homologous and six associated structural genes involved in anthocyanin biosynthesis in wheat were greatly up-regulated in the transgenic plants. Similarly, quantitative analysis for anthocyanin amounts based on HPLC-MS also confirmed that the transgenic wheat plants with combined overexpression of ZmC1 and ZmR accumulated the highest quantity of pigment products. Moreover, developing seeds overexpressing ZmR exposed to light conditions showed up-regulated transcript levels of anthocyanin biosynthesis-related genes compared to dark exposure, which suggests an important role of light in regulating anthocyanin biosynthesis. This study provides a foundation for breeding wheat materials with high anthocyanin accumulation and understanding the mechanism of anthocyanin biosynthesis in wheat.
Bisma Riaz, Haiqiang Chen, Jing Wang, Lipu Du, Ke Wang, Xingguo Ye. International Journal of Molecular Sciences, 20 (22), 5806, 2019.
Read the publicationPseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.
Alyssa C. McVey, Sean Bartlett, Mahmud Kajbaf, Annalisa Pellacani, Viviana Gatta, Päivi Tammela, David R. Spring, Martin Welch. International Journal of Molecular Sciences, 21 (7), 2490, 2020.
Read the publicationDietary trans fatty acids (TFAs) have been implicated in serious health risks, yet little is known about their cellular effects and metabolism. We aim to undertake an in vitro comparison of two representative TFAs (elaidate and vaccenate) to the best-characterized endogenous cis-unsaturated FA (oleate). The present study addresses the possible protective action of TFAs on palmitate-treated RINm5F insulinoma cells with special regards to apoptosis, endoplasmic reticulum stress and the underlying ceramide and diglyceride (DG) accumulation. Both TFAs significantly improved cell viability and reduced apoptosis in palmitate-treated cells. They mildly attenuated palmitate-induced XBP-1 mRNA cleavage and phosphorylation of eukaryotic initiation factor 2α (eIF2α) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but they were markedly less potent than oleate. Accordingly, all the three unsaturated FAs markedly reduced cellular palmitate incorporation and prevented harmful ceramide and DG accumulation. However, more elaidate or vaccenate than oleate was inserted into ceramides and DGs. Our results revealed a protective effect of TFAs in short-term palmitate toxicity, yet they also provide important in vitro evidence and even a potential mechanism for unfavorable long-term health effects of TFAs compared to oleate.
Farkas Sarnyai, Anna Somogyi, Zsófia Gór-Nagy, Veronika Zámbó, Péter Szelényi, Judit Mátyási, Laura Simon-Szabó, Éva Kereszturi, Blanka Tóth, Miklós Csala. International Journal of Molecular Sciences, 21 (7), 2626, 2020.
Read the publicationTacrolimus has been used to induce remission in patients with steroid-refractory ulcerative colitis. It poses a problem of large individual differences in dosage necessary to attain target blood concentration and, often, this leads to drug inefficacy. We examined the difference in mRNA expression levels of ATP binding cassette transporter B1 (ABCB1) between inflamed and non-inflamed tissues, and the influence of CYP3A5 genotype on tacrolimus therapy. The mRNA expression of CYP3A4 in colonic mucosa and that of cytochrome p450 3A5 (CYP3A5) and ABCB1 in inflamed and non-inflamed areas were examined in 14 subjects. The mRNA expression levels of CYP3A5 were higher than that of CYP3A4. The mRNA expression of ABCB1 was lower in the inflamed than in the non-inflamed mucosa, despite that of CYP3A5 mRNA level being not significantly changed. Hence, the deterioration of the disease is related to the reduction of the barrier in the inflamed mucosa. The relationship between CYP3A5 genotype and blood concentration, dose, and concentration/dose (C/D) ratio of tacrolimus in 15 subjects was studied. The tacrolimus dose to maintain equivalent blood concentrations was lower in CYP3A5*3/*3 than in CYP3A5*1 carriers, and the C/D ratio was significantly higher in the latter. Thus, CYP3A5 polymorphism information played a role in determining the initial dose of tacrolimus. Furthermore, since the effect of tacrolimus appears earlier in CYP3A5*3/*3 than in CYP3A5*1/*1 and *1/*3, it seems necessary to change the evaluation time of therapeutic effect by CYP3A5 genotype. Additionally, the relationship between CYP3A5 genotype and C/D ratio of tacrolimus in colonic mucosa was investigated in 10 subjects. Tacrolimus concentration in the mucosa was two-fold higher in CYP3A5*3/*3 than in CYP3A5*1 carriers, although no significant difference in tacrolimus-blood levels was observed. Therefore, the local concentration of tacrolimus affected by CYP3A5 polymorphism might be related to its therapeutic effect.
Yuki Yamamoto, Hiroshi Nakase, Minoru Matsuura, Shihoko Maruyama, Satohiro Masuda. International Journal of Molecular Sciences, 21 (12), 4347, 2020.
Read the publicationRestrictive feeding influences systemic metabolism of nutrients; however, this impact has not been evaluated in chickens of diverging feed efficiency. This study investigated the effect of ad libitum versus restrictive feeding (85% of ad libitum) on the serum metabolome and white blood cell composition in chickens of diverging residual feed intake (RFI; metric for feed efficiency). Blood samples were collected between days 33 and 37 post-hatch. While serum glucose was similar, serum uric acid and cholesterol were indicative of the nutritional status and chicken’s RFI, respectively. Feed restriction and RFI rank caused distinct serum metabolome profiles, whereby restrictive feeding also increased the blood lymphocyte proportion. Most importantly, 10 amino acids were associated with RFI rank in birds, whereas restrictive feeding affected almost all detected lysophosphatidylcholines, with 3 being higher and 6 being lower in restrictively compared to ad libitum fed chickens. As indicated by relevance networking, isoleucine, lysine, valine, histidine, and ornithine were the most discriminant for high RFI, whereas 3 biogenic amines (carnosine, putrescine, and spermidine) and 3 diacyl-glycerophospholipids (38:4, 38:5, and 40:5) positively correlated with feed intake and body weight gain, respectively. Only for taurine, feed intake mostly explained the RFI-associated variation, whereas for most metabolites, other host physiological factors played a greater role for the RFI-associated differences, and was potentially related to insulin-signaling, phospholipase A2, and arachidonic acid metabolism. Alterations in the hepatic synthesis of long-chain fatty acids and the need for precursors for gluconeogenesis due to varying energy demand may explain the marked differences in serum metabolite profiles in ad libitum and restrictively fed birds.
Barbara Metzler-Zebeli, Sina-Catherine Siegerstetter, Elizabeth Magowan, Peadar Lawlor, Niamh O’Connell, Qendrim Zebeli. Metabolites, 9 (2), 38, 2019.
Read the publicationTwo series of novel 5-arylazo-3-cyano-2-(2″,3″,4″,6″-tetra-O-acetyl-β-d-galacto pyranosyloxy) pyridines and 3-cyano-2-(2″,3″,4″,6″-tetra-O-acetyl-β-d-galactopyranosyloxy) pyridines were synthesized in high yields utilizing a microwave-assisted synthesis tool guided by the principles of green chemistry. The chemical structures of the new substances were confirmed on the basis of their elemental analysis and spectroscopic data (FT-IR, 1D, 2D-NMR). Activity against different bacterial strains was studied. The anticancer potential of the new compounds is also discussed. Molecular docking was used as a tool in this research work to get better insight into the possible interactions, affinities, and expected modes of binding of the most promising derivatives of the potential chemotherapeutic target (DHFR).
Majed Alrobaian, Sana Al Azwari, Amany Belal, Hany A. Eldeab. Molecules, 24 (10), 1969, 2019.
Read the publicationAn LC-MS/MS method for the identification and quantification of antidepressants and antipsychotics was developed on dried blood spots (DBSs). Moreover, analyte stability on DBSs within a 3-month period was monitored. Aliquots of 85 µL of blood from autopsy cases were pipetted onto DBS cards, which were dried and stored at room temperature. DBSs were analyzed in triplicate immediately, within the following 3 weeks, and after 3 months. For each analysis, a whole blood stain was extracted in phosphate buffer and purified using Solid Phase Extraction (SPE) cartridges in order to avoid matrix effects and injected in the LC-MS/MS system. Thirty-nine molecules were screened. Limits of detection (LODs) ranged between 0.1 and 3.2 ng/mL (g) and 0.1 and 5.2 ng/mL (g) for antidepressants and antipsychotics, respectively. Limits of quantification (LOQs) varied from 5 to 10.0 ng/mL for both. Sixteen cases among the 60 analyzed resulted positive for 17 different analytes; for 14 of these the method was fully validated. A general good agreement between the concentrations on DBSs and those measured in conventional blood samples (collected concurrently and stored at −20 °C) was observed. The degradation/enhancement percentage for most of the substances was lower than 20% within the 3-month period. Our results, obtained from real post-mortem cases, suggest that DBSs can be used for routine sample storage.
Matteo Moretti, Francesca Freni, Beatrice Valentini, Claudia Vignali, Angelo Groppi, Silvia Damiana Visonà, Antonio Marco Maria Osculati, Luca Morini. Molecules, 24 (20), 3636, 2019.
Read the publicationGemcitabine (dFdC) demonstrates significant effectiveness against solid tumors in vitro and in vivo; however, its clinical application is limited because it tends to easily undergo deamination metabolism. Therefore, we synthesized 4-N-carbobenzoxy-gemcitabine (Cbz-dFdC) as a lead prodrug and conducted a detailed pharmacokinetic, metabolic, and pharmacodynamic evaluation. After intragastric Cbz-dFdC administration, the Cmax of Cbz-dFdC and dFdC was 451.1 ± 106.7 and 1656.3 ± 431.5 ng/mL, respectively. The Tmax of Cbz-dFdC and dFdC was 2 and 4 h, respectively. After intragastric administration of Cbz-dFdC, this compound was mainly distributed in the intestine due to low carboxylesterase-1 (CES1) activity. Cbz-dFdC is activated by CES1 in both humans and rats. The enzyme kinetic curves were well fitted by the Michaelis–Menten equation in rats’ blood, plasma, and tissue homogenates and S9 of the liver and kidney, as well as human liver S9 and CES1 recombinase. The pharmacodynamic results showed that the Cbz-dFdC have a good antitumor effect in the HepG2 cell and in tumor-bearing mice, respectively. In general, Cbz-dFdC has good pharmaceutical characteristics and is therefore a good candidate for a potential prodrug.
Yilin Sun, Jiankun Wang, Kun Hao. Molecules, 25 (9), 2218, 2020.
Read the publication2,3,4-Tri-O-benzyl-D-xylopyranose was used as a starting material in the preparation of the corresponding triene, which underwent smooth cyclization to a polyhydroxylated hydrindane, as a single diastereoisomer. The analogous triene prepared from D-glucose did not undergo any cyclization even under high pressure.
Grzegorz Witkowski, Mykhaylo A. Potopnyk, Karolina Tiara, Anna Osuch-Kwiatkowska, Sławomir Jarosz. Molecules, 25 (15), 3357, 2020.
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