241 research outputs found
FRET-based assay of the processing reaction kinetics of stimulus-responsive peptides : influence of amino acid sequence on reaction kinetics
In the field of chemical biology, methods for controlling peptidyl function by a stimulus are attracting increasing attention. Recently, we reported a stimulus-responsive peptide which can be cleaved after exposure to a stimulus. In this study, we developed a FRET-based assay system to estimate the kinetics of the stimulus-induced processing (peptide bond cleavage) reaction. Based on the FRET system, it was clarified that introduction of a sterically less-hindered or polar residue at the position adjacent to the stimulus-responsive amino acid accelerates the processing reaction
Diagnostic Accuracy of Positron Emission Mammography with 18F-fluorodeoxyglucose in Breast Cancer Tumor of Less than 20 mm in Size
Objective(s): To investigate the diagnostic accuracy of positron emission mammography (PEM) and positron emission tomography/computed tomography (PET/CT) for small breast tumors of less than 20 mm in size.Methods: The study was conducted on a total of 100 subjects (i.e., 50 patients with pathologically proven breast cancer and 50 normal cases of medical screening). The total number of tumors was 54 (mean size: 11±5.1 mm, range:4-20 mm). The diagnostic accuracy of PEM alone, PET/CT alone, and combined PET/CT and PEM was evaluated by two nuclear medicine physicians based on visual inspection. The two groups (i.e., tumors of ≤ 10 mm and > 10-20 mm) werecompared in terms of the diagnostic capability of the three modalities (PEM alone, PET/CT alone, and PET/CT+PEM).Results: The sensitivities of PEM alone, PET/CT alone, and combined PET/CT and PEM were 72%, 60%, and 76%, respectively. The specificities of these tests were 98%, 100%, and 98%, respectively. Furthermore, the accuracies of these diagnostic modalities were 85%, 79%, and 87%, respectively. The combined PET/CT and PEM showed significantly higher sensitivity and accuracy than PET/CT alone (P=0.005 and P=0.02, respectively). In addition, PEM demonstrated asignificantly higher sensitivity than PET/CT in the ≤ 10 mm group (P=0.03); however, no difference was observed between the two modalities in the > 10 mm group in terms of sensitivity.Conclusion: 18F-fluorodeoxyglucose PET had limited capability for the detection of small breast cancers of < 10 mm. Combined PET/CT and PEM showed higher sensitivity and accuracy, compared to PET/CT alone
Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures
The structures of the ligand-binding domains (LBDs) of human peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ) in complexes with a pan agonist, an α/δ dual agonist and a PPARδ-specific agonist were determined. The results explain how each ligand is recognized by the PPAR LBDs at an atomic level
Development of thiol-responsive amide bond cleavage device and its application for peptide nucleic acid-based DNA releasing system
To develop a thiol-responsive DNA releasing system, a thiol-responsive amino acid capable of inducing an amide bond cleavage in the presence of a thiol was developed. It was successfully combined with peptide nucleic acid (PNA), and thiol-induced release of DNA from the thiol-responsive PNA/DNA complex was observed
Development of a Reduction‐Responsive Amino Acid that Induces Peptide Bond Cleavage in Hypoxic Cells
Utilization of a hypoxia-responsive amino acid is indispensable in the preparation of hypoxic tumor-specific peptidyl prodrugs. Bioreduction of a nitro group is among the most attractive triggering reactions in the hypoxia-responsive prodrugs. In this paper, design and synthesis of a reduction-responsive amino acid that induces peptide bond cleavage after reduction of the nitro group are described. Application to hypoxia-responsive peptide bond cleavage system is also reported
Design and synthesis of caged ceramide : UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O–N acyl transfer
Sphingolipids, recognized as membrane constructs and as key signaling molecules, have been studied to examine intracellular function. Some caged sphingolipids that release parent sphingolipids after exposure to UV-irradiation have been previously developed, but caged ceramide has yet to be reported. In this study, we report the design and synthesis of a caged ceramide. Photo-irradiation experiment clarified that the caged ceramide can be successfully converted to the parent ceramide by UV-irradiation. Introduction of an alkyne-handle moiety for further modification of the caged ceramide is also reported
Development of a Reduction‐Responsive Amino Acid that Induces Peptide Bond Cleavage in Hypoxic Cells
Utilization of a hypoxia-responsive amino acid is indispensable in the preparation of hypoxic tumor-specific peptidyl prodrugs. Bioreduction of a nitro group is among the most attractive triggering reactions in the hypoxia-responsive prodrugs. In this paper, design and synthesis of a reduction-responsive amino acid that induces peptide bond cleavage after reduction of the nitro group are described. Application to hypoxia-responsive peptide bond cleavage system is also reported
CLE Peptides can Negatively Regulate Protoxylem Vessel Formation via Cytokinin Signaling
Cell–cell communication is critical for tissue and organ development. In plants, secretory CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptides function as intercellular signaling molecules in various aspects of tissue development including vascular development. However, little is known about intracellular signaling pathways functioning in vascular development downstream of the CLE ligands. We show that CLE peptides including CLE10, which is preferentially expressed in the root vascular system, inhibit protoxylem vessel formation in Arabidopsis roots. GeneChip analysis displayed that CLE10 peptides repressed specifically the expression of two type-A Arabidopsis Response Regulators (ARRs), ARR5 and ARR6, whose products act as negative regulators of cytokinin signaling. The arr5 arr6 roots exhibited defective protoxylem vessel formation. These results indicate that CLE10 inhibits protoxylem vessel formation by suppressing the expression of type-A ARR genes including ARR5 and ARR6. This was supported by the finding that CLE10 did not suppress protoxylem vessel formation in a background of arr10 arr12, a double mutant of type-B ARR genes. Thus, our results revealed cross-talk between CLE signaling and cytokinin signaling in protoxylem vessel formation in roots. Taken together with the indication that cytokinin signaling functions downstream of the CLV3/WUS signaling pathway in the shoot apical meristem, the cross-talk between CLE and cytokinin signaling pathways may be a common feature in plant development
Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT)
The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT).
Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard.
In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT.
The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results
Effect of Kampo medicine “Dai-kenchu-to” on microbiome in the intestine of the rats with fast stress
[Purpose] Diversity of gut microbiome has been recently reported to be lost in inflammatory bowel disease. We have previously reported that the Dai-kenchu-to (DKT) prevented the bacterial translocation through suppression of cytokine and apoptosis in rat’s fast stress model. The aim of this study was to evaluate the effect of DKT on maintenance of microbial diversity in rat’s intestine with inflammation. [Method] Wister rats were received the fast stress for 5 days. In DKT group, rats were administered with DKT (300 mg/kg/day) during the fast stress (DKT-group). The gut microbiomes were analyzed at before- and after- fast stress, and the effect of DKT for on microbial diversities of the gut were evaluated by the PCR-clone library method targeting the 16 S ribosomal RNA gene. [Result] In Control-group, Erysipelotrichaceae increased to 86% in after fast stress, OTU of before-fast stress was 111 and after fast stress was only 9 (changing rate : 58%). The diversity of microbiome was severely decreased. On the other hand, in DKT-group, diversity of microbiome was kept after fast stress (Lachnospiraceae : Ruminococcaceae : Coriobacteriales 54%, 22%, 5%), Operational taxonomic units of before fast stress was 52 and after fast stress was 55 (changing rate : 6%). Family Lachnospiraceae which includes butyrate-producing Clostridia (Clostridium IV and XIVa). [Conclusion] DKT prevented the reduction of diversity of microbiome in rat’s fast stress model. Our data suggested the new anti-inflammatory mechanism of DKT through gut microbiome
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