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Journal of Natural Products Apr 2010Three new phorbasides (G-I), chlorocyclopropyl ene-yne macrolide glycosides, were isolated from the sponge Phorbas sp. in yields of 7-9.5 mug and fully characterized by...
Three new phorbasides (G-I), chlorocyclopropyl ene-yne macrolide glycosides, were isolated from the sponge Phorbas sp. in yields of 7-9.5 mug and fully characterized by MS, CD, and microcryoprobe NMR. The structures of the new compounds differ only in the nature of the sugar residues. The absolute configurations of the new compounds were correlated by ROESY and CD with the parent compounds phorbasides A and B.
Topics: Animals; Glycosides; Macrolides; Molecular Structure; Nanotechnology; Nuclear Magnetic Resonance, Biomolecular; Porifera
PubMed: 20184337
DOI: 10.1021/np1000297 -
Plant Physiology Jun 1988Concentrations of polyamines (PA) and the activities of the PA-synthesizing enzymes ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) extracted from the...
Concentrations of polyamines (PA) and the activities of the PA-synthesizing enzymes ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) extracted from the mesocarp tissue of avocado (Persea americana Mill, cv ;Simmonds') fruits at different stages of development were compared with DNA content and the activities of 5'-methylthioadenosine (MTA) nucleosidase and 5-methylthioribose (MTR) kinase. Putrescine, spermidine, and spermine were at their peak concentrations during the early stages of fruit development (362, 201, and 165 nanomoles per gram fresh weight, respectively, at 15 days from full bloom), then declined to 30% or less at full maturity. Agmatine showed only a slight change in concentration throughout the fruit development. The activity of ODC, which was low during flowering (8 nmoles per milligram protein per hour), increased more than threefold during the first 2 months then declined at the later stages of fruit development, while ADC activity showed only a slight increase. DNA content followed a similar pattern of change as that of PA and ODC. The decline in DNA and ODC activity suggest a lack of correlation between cell proliferation and PA at the later stages of the avocado fruit development. It is also possible that any cell division which may take place during the latter stages of the fruit development is not sufficient to alter the pattern of PA biosynthesis. MTA nucleosidase and MTR kinase activities increased during the first 15 days of fruit development followed by a slight decline at 60 and 90 days from full bloom. At 120 days (1 month before full maturity) both MTA nucleosidase and MTR kinase activities increased significantly. During maximum ethylene synthesis, MTA nucleosidase and MTR kinase activities were approximately fivefold and eightfold, respectively, higher than during maximum PA synthesis. The data indicate that the MTA molecules produced during PA and ethylene synthesis are actively metabolized to MTR and MTR-1-P, the two intermediates involved in the regeneration of S-adenosylmethionine from MTA. The data also suggest that the PA and ethylene biosynthetic pathways are not actively competing for the same substrates at any given stage of the avocado fruit development and ripening.
PubMed: 16666165
DOI: 10.1104/pp.87.2.463 -
Nature Communications Apr 2023HMBC is an essential NMR experiment for determining multiple bond heteronuclear correlations in small to medium-sized organic molecules, including natural products, yet...
HMBC is an essential NMR experiment for determining multiple bond heteronuclear correlations in small to medium-sized organic molecules, including natural products, yet its major limitation is the inability to differentiate two-bond from longer-range correlations. There have been several attempts to address this issue, but all reported approaches suffer various drawbacks, such as restricted utility and poor sensitivity. Here we present a sensitive and universal methodology to identify two-bond HMBC correlations using isotope shifts, referred to as i-HMBC (isotope shift detection HMBC). Experimental utility was demonstrated at the sub-milligram / nanomole scale with only a few hours of acquisition time required for structure elucidation of several complex proton-deficient natural products, which could not be fully elucidated by conventional 2D NMR experiments. Because i-HMBC overcomes the key limitation of HMBC without significant reduction in sensitivity or performance, i-HMBC can be used as a complement to HMBC when unambiguous identifications of two-bond correlations are needed.
PubMed: 37012241
DOI: 10.1038/s41467-023-37289-z -
PloS One 2022Aberration of PI3K signaling pathway has been confirmed to be associated with several hematological malignancies including acute myeloid leukemia (AML). FD268, a...
Aberration of PI3K signaling pathway has been confirmed to be associated with several hematological malignancies including acute myeloid leukemia (AML). FD268, a pyridinesulfonamide derivative characterized by the conjugation of 7-azaindole group, is a newly identified PI3K inhibitor showing high potent enzyme activity at nanomole concentration. In this study, we demonstrated that FD268 dose-dependently inhibits survival of AML cells with the efficacy superior to that of PI-103 (pan-PI3K inhibitor) and CAL-101 (selective PI3Kδ inhibitor) in the tested HL-60, MOLM-16, Mv-4-11, EOL-1 and KG-1 cell lines. Further mechanistic studies focused on HL-60 revealed that FD268 significantly inhibits the PI3K/Akt/mTOR signaling pathway, promotes the activation of pro-apoptotic protein Bad and downregulates the expression of anti-apoptotic protein Mcl-1, thus suppressing the cell proliferation and inducing caspase-3-dependent apoptosis. The bioinformatics analysis of the transcriptome sequencing data also indicated a potential involvement of the PI3K/Akt/mTOR pathway. These studies indicated that FD268 possesses high potent activity toward AML cells via inhibition of PI3K/Akt/mTOR signaling pathway, which sheds some light on the pyridinesulfonamide scaffold for further optimization and investigation.
Topics: Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Apoptosis; Cell Proliferation; Phosphoinositide-3 Kinase Inhibitors; Leukemia, Myeloid, Acute
PubMed: 36413544
DOI: 10.1371/journal.pone.0277893 -
Frontiers in Medical Technology 2023Fluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore,...
BACKGROUND
Fluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for surgical guidance during head and neck squamous cell carcinoma (HNSCC) resection. However, tumor-to-normal tissue contrast is confounded by intrinsic physiological limitations of heterogeneous EGFR expression and non-specific agent uptake.
OBJECTIVE
In this preliminary study, radiomic analysis was applied to optical ABY-029 fluorescence image data for HNSCC tissue classification through an approach termed "optomics." Optomics was employed to improve tumor identification by leveraging textural pattern differences in EGFR expression conveyed by fluorescence. The study objective was to compare the performance of conventional fluorescence intensity thresholding and optomics for binary classification of malignant vs. non-malignant HNSCC tissues.
MATERIALS AND METHODS
Fluorescence image data collected through a Phase 0 clinical trial of ABY-029 involved a total of 20,073 sub-image patches (size of 1.8 × 1.8 mm) extracted from 24 bread-loafed slices of HNSCC surgical resections originating from 12 patients who were stratified into three dose groups (30, 90, and 171 nanomoles). Each dose group was randomly partitioned on the specimen-level 75%/25% into training/testing sets, then all training and testing sets were aggregated. A total of 1,472 standardized radiomic features were extracted from each patch and evaluated by minimum redundancy maximum relevance feature selection, and 25 top-ranked features were used to train a support vector machine (SVM) classifier. Predictive performance of the SVM classifier was compared to fluorescence intensity thresholding for classifying testing set image patches with histologically confirmed malignancy status.
RESULTS
Optomics provided consistent improvement in prediction accuracy and false positive rate (FPR) and similar false negative rate (FNR) on all testing set slices, irrespective of dose, compared to fluorescence intensity thresholding (mean accuracies of 89% vs. 81%, = 0.0072; mean FPRs of 12% vs. 21%, = 0.0035; and mean FNRs of 13% vs. 17%, = 0.35).
CONCLUSIONS
Optomics outperformed conventional fluorescence intensity thresholding for tumor identification using sub-image patches as the unit of analysis. Optomics mitigate diagnostic uncertainties introduced through physiological variability, imaging agent dose, and inter-specimen biases of fluorescence molecular imaging by probing textural image information. This preliminary study provides a proof-of-concept that applying radiomics to fluorescence molecular imaging data offers a promising image analysis technique for cancer detection in fluorescence-guided surgery.
PubMed: 36875185
DOI: 10.3389/fmedt.2023.1009638 -
Sensors (Basel, Switzerland) Jan 2020The development of sensitive methods for in situ detection of biomarkers is a real challenge to bring medical diagnosis a step forward. The proof-of-concept of a remote...
The development of sensitive methods for in situ detection of biomarkers is a real challenge to bring medical diagnosis a step forward. The proof-of-concept of a remote multiplexed biomolecular interaction detection through a plasmonic optical fiber bundle is demonstrated here. The strategy relies on a fiber optic biosensor designed from a 300 µm diameter bundle composed of 6000 individual optical fibers. When appropriately etched and metallized, each optical fiber exhibits specific plasmonic properties. The surface plasmon resonance phenomenon occurring at the surface of each fiber enables to measure biomolecular interactions, through the changes of the retro-reflected light intensity due to light/plasmon coupling variations. The functionalization of the microstructured bundle by multiple protein probes was performed using new polymeric 3D-printed microcantilevers. Such soft cantilevers allow for immobilizing the probes in micro spots, without damaging the optical microstructures nor the gold layer. We show here the potential of this device to perform the multiplexed detection of two different antibodies with limits of detection down to a few tenths of nanomoles per liter. This tool, adapted for multiparametric, real-time, and label free monitoring is minimally invasive and could then provide a useful platform for in vivo targeted molecular analysis.
Topics: Animals; Antibodies; Biosensing Techniques; Equipment Design; Gold; Limit of Detection; Optical Fibers; Rats; Surface Plasmon Resonance; Surface Properties
PubMed: 31963277
DOI: 10.3390/s20020511 -
Chemical Senses Jul 2013A novel delivery method is described that incorporates taste stimuli into edible strips for determining n-propylthiouracil (PROP) taster status. Edible strips that... (Clinical Trial)
Clinical Trial
A novel delivery method is described that incorporates taste stimuli into edible strips for determining n-propylthiouracil (PROP) taster status. Edible strips that contained 400 or 600 nanomoles of PROP were prepared for psychophysical studies. Using these strips, we measured taste intensity, taste hedonics, and taste quality responses in a sample of healthy volunteers (n = 118). Participants were also asked to assess a single NaCl strip, a quinine strip, 3 NaCl solutions, and 3 PROP solutions. All psychophysical data were subsequently analyzed as a function of TAS2R38 genotype. The use of PROP strips for distinguishing between individuals with at least 1 PAV allele and individuals with other genotypes was assessed and compared with the use of PROP solutions for making this same distinction. For the 2 PROP strips and PROP solutions, individuals who expressed at least 1 PAV allele could perceive the bitter taste of PROP. Individuals who expressed 2 AVI alleles responded similarly to 400 nanomole PROP strips and blank strips. Furthermore, individuals with 2 AVI alleles responded to 0.032 and 0.32 mM PROP solutions at intensities that were similar to water, though intensity ratings to 3.2 mM PROP solution exceeded water. In general, those with at least 1 PAV allele rated the bitter taste of PROP as unpleasant in both delivery methods (strips or solutions). Psychophysical data from PROP strips and solutions were consistent with TAS2R38 genotype. These results support the validity of edible taste strips as a method for assessing PROP taste perception in humans.
Topics: Adolescent; Adult; Aged; Female; Genotype; Humans; Male; Middle Aged; Propylthiouracil; Receptors, G-Protein-Coupled; Reproducibility of Results; Taste Perception; Taste Threshold; Young Adult
PubMed: 23761681
DOI: 10.1093/chemse/bjt023 -
Angewandte Chemie (International Ed. in... Jun 2018Machines learn chemistry: An artificial intelligence algorithm has learned to predict the outcomes of C-N coupling reactions from a few thousand nanomole-scale...
Machines learn chemistry: An artificial intelligence algorithm has learned to predict the outcomes of C-N coupling reactions from a few thousand nanomole-scale experiments. This Highlight discusses this work in the context of other state-of-the-art approaches for predicting the yields of organic reactions and explains the significance of the results.
PubMed: 29701305
DOI: 10.1002/anie.201803562 -
Journal of Biomedical Optics Mar 2018Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence...
Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt this type of imaging in vivo.
Topics: Humans; Image Processing, Computer-Assisted; Optical Imaging; Phantoms, Imaging; Radiotherapy; Signal-To-Noise Ratio
PubMed: 29560623
DOI: 10.1117/1.JBO.23.3.030504 -
The Journal of Nutrition Sep 2017Serum folate methods produce different results. The comparability of HPLC-mass spectrometry (MS)/MS methods is not well documented. We conducted an international... (Comparative Study)
Comparative Study
Two International Round-Robin Studies Showed Good Comparability of 5-Methyltetrahydrofolate but Poor Comparability of Folic Acid Measured in Serum by Different High-Performance Liquid Chromatography-Tandem Mass Spectrometry Methods.
Serum folate methods produce different results. The comparability of HPLC-mass spectrometry (MS)/MS methods is not well documented. We conducted an international "round-robin" investigation to assess the comparability, precision, and accuracy of serum folate HPLC-MS/MS methods. The CDC laboratory, 7 laboratories with independently developed methods (group 1), and 6 laboratories with an adapted CDC method (group 2) analyzed folate forms in 6 serum pools and 6 calibrators from the CDC (duplicate analysis over 2 d) and in two 3-level reference materials (duplicate analysis). All laboratories measured 5-methyltetrahydrofolate (5-methylTHF) and folic acid; some measured additional folate forms. The geometric mean (range) concentrations (nanomoles per liter) for 5-methylTHF in the 6 serum pools were 18.3 nmol/L (CDC), 13.8-28.9 nmol/L (group 1), and 16.8-18.6 nmol/L (group 2); for folic acid the concentrations were 3.42 nmol/L (CDC), 1.09-4.74 nmol/L (group 1), and 1.74-2.90 nmol/L (group 2). The median imprecision (CV) for 5-methylTHF was 4.1% (CDC), 4.6-11% (group 1), and 1.7-6.0% (group 2); for folic acid it was 6.9% (CDC), 4.9-20% (group 1), and 3.9-23% (group 2). The mean ± SD (range) recovery of 5-methylTHF spiked into serum was 98% ± 27% (59-138%) for group 1 and 98% ± 10% (82-111%) for group 2; for folic acid it was 93% ± 29% (67-198%) for group 1 and 81% ± 16% (64-102%) for group 2. The mean relative bias for 5-methylTHF compared with the reference material certificate value was 12% (CDC), -24% to 30% (group 1), and -0.6% to 16% (group 2); for folic acid it was 73% (CDC), -47% to 578% (group 1), and -3.3% to 67% (group 2). For 5-methylTHF, group 2 laboratories demonstrated better agreement and precision, less variable spiking recovery, and less bias by using a reference material. Laboratory performance for folic acid was highly variable and needs improvement. Certified reference materials for serum folate forms and total folate are needed to improve method accuracy.
Topics: Calibration; Chromatography, High Pressure Liquid; Folic Acid; Humans; Laboratories; Nutritional Status; Reference Values; Tandem Mass Spectrometry; Tetrahydrofolates
PubMed: 28768831
DOI: 10.3945/jn.117.254144