AbstractThe paw paw tree, Asimina triloba. (L.) Dunal (Annonaceae), contains more than 50 bioactive components, primarily annonaceous acetogenins. Some therapeutic activities have been associated with this material, but the potential to mediate a cancer chemopreventive effect has not been reported. In this study, a standardized extract from the twigs, in which bullatacin, asimicin, and trilobacin represent the most potent and major bioactive acetogenins, was tested in the N.-methyl-N.-nitrosourea–induced mammary carcinogenesis model. With Sprague-Dawley rats given a diet containing paw paw extract (1250 and 2500 mg/kg diet; based on maximum tolerated dose studies), mammary tumor latency was increased from 55 to 66 days. However, mammary tumor incidence and multiplicity were not affected by extract consumption. 相似文献
Background and aimsEfficient analysis strategies for complex network with cardiovascular disease (CVD) risk stratification remain lacking. We sought to identify an optimized model to study CVD prognosis using survival conditional inference tree (SCTREE), a machine-learning method.Methods and resultsWe identified 5379 new onset CVD from 2006 (baseline) to May, 2017 in the Kailuan I study including 101,510 participants (the training dataset). The second cohort composing 1,287 CVD survivors was used to validate the algorithm (the Kailuan II study, n = 57,511). All variables (e.g., age, sex, family history of CVD, metabolic risk factors, renal function indexes, heart rate, atrial fibrillation, and high sensitivity C-reactive protein) were measured at baseline and biennially during the follow-up period. Up to December 2017, we documented 1,104 deaths after CVD in the Kailuan I study and 170 deaths in the Kailuan II study. Older age, hyperglycemia and proteinuria were identified by the SCTREE as main predictors of post-CVD mortality. CVD survivors in the high risk group (presence of 2–3 of these top risk factors), had higher mortality risk in the training dataset (hazard ratio (HR): 5.41; 95% confidence Interval (CI): 4.49–6.52) and in the validation dataset (HR: 6.04; 95%CI: 3.59–10.2), than those in the lowest risk group (presence of 0–1 of these factors).ConclusionOlder age, hyperglycemia and proteinuria were the main predictors of post-CVD mortality.Trial registrationChiCTR-TNRC-11001489. 相似文献
Many drugs are nature derived. Low drug productivity has renewed interest in natural products as drug-discovery sources. Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary-metabolite gene clusters in selected species. It can be hypothesized that drug-like structures probably are distributed in selective groups of species. We compared the species origins of 939 approved and 369 clinical-trial drugs with those of 119 preclinical drugs and 19,721 bioactive natural products. In contrast to the scattered distribution of bioactive natural products, these drugs are clustered into 144 of the 6,763 known species families in nature, with 80% of the approved drugs and 67% of the clinical-trial drugs concentrated in 17 and 30 drug-prolific families, respectively. Four lines of evidence from historical drug data, 13,548 marine natural products, 767 medicinal plants, and 19,721 bioactive natural products suggest that drugs are derived mostly from preexisting drug-productive families. Drug-productive clusters expand slowly by conventional technologies. The lack of drugs outside drug-productive families is not necessarily the result of under-exploration or late exploration by conventional technologies. New technologies that explore cryptic gene clusters, pathways, interspecies crosstalk, and high-throughput fermentation enable the discovery of novel natural products. The potential impact of these technologies on drug productivity and on the distribution patterns of drug-productive families is yet to be revealed. 相似文献