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Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.
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Objective@#To observe the evaluation function of gated equilibration ventriculography for the changes of left ventricular function in breast cancer with targeted therapy.@*Methods@#From February 2016 to December 2017, a total of 60 female breast cancer patients (age: 28-65 (48.7±9.4) years) were included prospectively. Patients were divided into 2 groups: lapatinib combined with taxeme-based chemotherapy group (group A; n=25, age: 29-65 (47.8±11.3) years) and lapatinib monotherapy group (group B; n=35, age: 31-62 (51.1±8.5) years). All patients underwent gated equilibration ventriculography before treatment and 6/12 months after treatment. The parameters of left ventricular function including left ventricle ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), 1/3 ejection fraction (EF), 1/3 filling fraction (FF), time to peak ejection rate (TPER) and time of peak filling rate (TPFR) were observed. Repeated measurement analysis of variance, independent-samples t test and Wilcoxon rank sum test were performed.@*Results@#In group A, the PER at 12 months after treatment ((3.11±0.48) end-diastolic volume (EDV)/s) was lower than that before treatment ((3.60±0.62) EDV/s; F=3.447, t=0.60, P<0.05), while there was no statistical difference between PER at 6 months after treatment ((3.34±0.57) EDV/s) and that before treatment (t=0.51, P>0.05); the PFR at 6 months ((3.07±0.71) EDV/s) and 12 months after treatment ((2.84±0.54) EDV/s) declined significantly compared with that before treatment ((3.57±0.81) EDV/s; F=5.345, t=0.82 and 0.75, both P<0.05). In group B, the PFR at 12 months after treatment ((2.86±0.55) EDV/s) declined significantly compared with that before treatment ((3.23±0.87) EDV/s; F=3.214, t=0.84, P<0.05). The decrease of PFR at 6 months and 12 months after treatment in group A was greater than that in group B (-0.37(-0.78, 0.15) vs -0.13(-0.44, 0.17) EDV/s; z=-1.569, P<0.05).@*Conclusions@#The gated equilibration ventriculography can effectively monitor the left ventricular function of breast cancer patients after targeted therapy. PER and PFR may be more sensitive than other parameters to assess heart function changes. The lapatinib combined with taxeme-based chemotherapy can affect diastolic function more and earlier than lapatinib monotherapy.
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Objective To observe the evaluation function of gated equilibration ventriculography for the changes of left ventricular function in breast cancer with targeted therapy. Methods From February 2016 to December 2017, a total of 60 female breast cancer patients (age:28-65 (48.7±9.4) years) were included prospectively. Patients were divided into 2 groups: lapatinib combined with taxeme-based chemo-therapy group (group A;n=25, age:29-65 (47.8±11.3) years) and lapatinib monotherapy group (group B;n=35, age:31-62 (51.1±8.5) years). All patients underwent gated equilibration ventriculography be-fore treatment and 6/12 months after treatment. The parameters of left ventricular function including left ven-tricle ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), 1/3 ejection fraction (EF), 1/3 filling fraction (FF), time to peak ejection rate (TPER) and time of peak filling rate (TPFR) were observed. Repeated measurement analysis of variance, independent-samples t test and Wilcoxon rank sum test were performed. Results In group A, the PER at 12 months after treatment ((3.11±0.48) end-di-astolic volume (EDV)/s) was lower than that before treatment ((3.60±0.62) EDV/s;F=3.447, t=0.60, P<0. 05), while there was no statistical difference between PER at 6 months after treatment ((3.34±0.57) EDV/s) and that before treatment (t=0.51, P>0. 05);the PFR at 6 months ((3.07±0.71) EDV/s) and 12 months after treatment ((2.84±0.54) EDV/s) declined significantly compared with that before treatment ((3. 57± 0. 81) EDV/s;F=5.345, t=0.82 and 0.75, both P<0. 05) . In group B, the PFR at 12 months after treat-ment ((2.86±0.55) EDV/s) declined significantly compared with that before treatment ((3.23±0. 87) EDV/s;F=3.214, t=0.84, P<0. 05) . The decrease of PFR at 6 months and 12 months after treatment in group A was greater than that in group B (-0.37(-0.78, 0. 15) vs -0.13(-0.44, 0.17) EDV/s; z=-1.569, P<0. 05) . Conclusions The gated equilibration ventriculography can effectively monitor the left ventricular function of breast cancer patients after targeted therapy. PER and PFR may be more sensitive than other pa-rameters to assess heart function changes. The lapatinib combined with taxeme-based chemotherapy can af-fect diastolic function more and earlier than lapatinib monotherapy.
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Background and purpose: 18F-FDG has been considered to be of limited value for the detection of bladder lesions because of interference by the 18F-FDG excreted in urine. Delayed pelvic images with“diluted and iflled bladder”use a method of 18F-FDG PET/CT with delayed images after oral hydration so as to increase the detection rate of 18F-lfuorodeoxyglucose(FDG) PET/CT imaging for the lesions of bladder. Methods:48 patients with bladder lesions(35 patients with bladder primary tumor and 13 patients with metastatic tumor) underwent 18F-FDG PET/CT detection and were required oral hydration of 1200-1800 mL water, urination frequently, holding urine when the more scan began. Lesions conifrmed by histopathology, MRI, CT or clinical follow-up at least 1 year. Results:89%(43/48) of patients were obtained good clearance and the urine SUVmax declined from 33.14(9-66.80)to 3.23(1.35-5.65) signiifcantly and the statistical difference was signiifcant (t=8.703, P<0.01). The interval time between two scan was 2 h approximately. At the same time, the SUVmax of bladder lesion was 2.8-25.0. Detection sensitivity, speciifcity and accuracy were 90.47%(19/21), 81.48%(22/27)and 85.41%(41/48), respectively. Conclusion: 18F-FDG activity in the bladder signiifcantly decreased in most patients with“diluted and iflled bladder”. The PET/CT scan can highly detect lesions of bladder tissues. Our method with high accuracy and better endurance could be applied to detect the lesions in bladder.