Search results for "DISCOVERY"
showing 10 items of 4119 documents
Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3' UTRs Identified by Cellular Library Screening.
2019
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) …
Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.
2020
Graphical abstract
Exploring the anticancer potential of pyrazolo[1,2-a]benzo[1,2,3,4] tetrazin-3-one derivatives: The effect on apoptosis induction, cell cycle and pro…
2013
In order to investigate their anticancer potential, four new pyrazolo[1,2-a]benzo[1,2,3,4]-tetrazinone derivatives, designed through the chemometric protocol VLAK, and three of the most active compounds of the previous series have been evaluated on some cellular events including proliferation, apoptosis induction, and cell cycle. The NCI one dose (10 mu M) screening revealed that the 8,9-di-methyl derivative showed activity against Leukemia (CCRF-CEM) and Colon cancer cell line (COLO 205), reaching 81% and 45% of growth inhibition (GI), respectively. Replacement of the two methyl groups with two chlorine atoms maintained the activity toward Leukemia cell (CCRF-CEM, GI 77%) and selectively e…
The Italian Version of the Adult Vaccine Hesitancy Scale (aVHS) for the Working-Age Population: Cross-Cultural Adaptation, Reliability, and Validity
2022
The adult Vaccine Hesitancy Scale (aVHS) is valid and reliable for evaluating attitudes toward vaccine preventable diseases (VPDs). The aim of the present study was to evaluate the cross-cultural adaptation, reliability, and validity of the Italian version of the aVHS. After cross-cultural adaptation of the aVHS, internal consistency (IC), intra-class correlation (ICC), and content validity (S-CVI) were evaluated through a survey on 160 workers. Results of the ICC were analyzed on questionnaires administered twice at a distance of two months and revealed a satisfactory reproducibility (0.87). The IC of the aVHS was assessed by the Cronbach alpha coefficient test, with a result of 0.94, demo…
1H-naphtho[2,1-b]thiete and 2H-naphtho[2,3-b]thiete- synthesis and reactivity
1994
Abstract The title compounds 4 and 8 are obtained by flash vacuum pyrolysis of the corresponding hydroxymethylthionaphthols 3 and 7. Whereas 4 shows a smooth ring opening on heating, 8 is thermally stable but reacts photochemically. The different behavior is explained on the basis of an MNDO calculation. The valence isomers 4′ and 8′ represent thioquinonemethides, which are highly reactive components in [12π + 2π]cycloaddition processes (4 → 9, 10, 11; 8 → 12).
[1,2,3]Triazoloazine/(Diazomethyl)azine Valence Tautomers from 5-Azinyltetrazoles
1978
[1,2,3]Triazoloazines are formed by thermolysis of 5-azinyltetrazoles in the gasphase or in solution. Thus, 5-(2-pyridyl)tetrazole (7) and 5-(2-pyrazinyl)tetrazole (11) yield [1,2,3]triazolo[1,5-a]pyridine (9) and [1,2,3]triazolo[1,5-a]pyrazine (13), respectively, at 400°/10−3 - 10−5 Torr. 5-(2-Phenyl-4-quinazolinyl)tetrazole (15) gives 5-phenyl[1,2,3]triazolo[1,5-c]quinazoline (17) in 75% yield by heating under reflux in mesitylene solution. 2-(Diazomethyl)pyridine (8), a valence tautomer of 9, can be trapped by fumaronitrile, leading to 3-(2-pyridyl)-1, 2-cyclopropanedicarbonitrile (19). The [1,2,3]triazoloazines undergo base catalysed H/D-exchange in D2O solution.
Medicinal Plants for Insomnia Related to Anxiety: An Updated Review.
2021
AbstractSleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. The process entailed a search of PubMed, Scopus, and the Cochrane Library databases from 2010 to 2020. The search terms included “sleep d…
Synthesis of honokiol analogues and evaluation of their modulating action on VEGF protein secretion and telomerase-related gene expressions
2017
A group of 36 biphenyl derivatives structurally related to honokiol were synthesized by means of Suzuki coupling reactions. Their cytotoxicities were evaluated and compared to that of honokiol. Some of the compounds were then evaluated for their ability to downregulate the secretion of the VEGF protein and the expression of the VEGF, hTERT, and c-Myc genes; the two latter involved in the activation of telomerase in tumoral cells. Some of the synthetized derivatives showed promising pharmacological features as they exhibited IC50 values in low micromolar range, good therapeutic margins, and a multiple mode of action on tumor cells based on the inhibition of VEGF and, at the same time, of the…
Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tub…
2020
Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3&prime
Arthrinins A–D: Novel diterpenoids and further constituents from the sponge derived fungus Arthrinium sp.
2011
Bioassay-guided fractionation of a methanolic extract of the fungus Arthrinium sp., isolated from the Mediterranean sponge Geodia cydonium, afforded 10 natural products including five new diterpenoids, arthrinins A-D (1-4) and myrocin D (5). In addition, five known compounds were obtained, which included myrocin A (6), norlichexanthone (7), anomalin A (8), decarboxycitrinone (9) and 2,5-dimethyl-7-hydroxychromone (10). The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR and HR-MS analyzes. The absolute configuration of arthrinins A-D (1-4) was established by the convenient Mosher method performed in NMR tubes and by interpretation of the R…