ABSTRACT
Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.
Subject(s)
Antineoplastic Agents , Ovarian Neoplasms , Prodrugs , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cisplatin/pharmacology , Cisplatin/therapeutic use , Female , Humans , Lactones , Ovarian Neoplasms/drug therapy , Platinum/pharmacology , Platinum/therapeutic use , Polyethylene Glycols/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , Sesquiterpenes, EudesmaneABSTRACT
BACKGROUND: Blackened intestines in slaughtered pigs have been commonly observed in China in recent years. However, no cause has been reported. OBJECTIVES: We attempted to determine whether the blackening of the pig intestine was related to an excess of copper (Cu) in their feed. METHODS: In this study, we observed and collected porcine intestines in small- and large-scale pig slaughterhouses in Shandong province from May to October 2018. Twelve types of metal ions were detected in the black intestinal samples. RESULTS: The Cu level in the intestine samples was mostly higher than the Chinese national limit for food. Further study showed that Cu supplementation in most commercial porcine feed also exceeded the national standard. An animal model (mouse) that could mimic the intestinal blackening in pigs was established. Compared to control mice, Cu accumulated in the liver and intestines of mice fed an excessive Cu level, confirming the excessive Cu in the feed may be considered the major cause of blackened porcine intestines. Microscopic examination revealed that black intestines had many particles containing Cu in the lamina propria of the intestinal mucosa, and the intestinal mucosal epithelial cells showed degeneration and necrosis. CONCLUSIONS: In conclusion, overuse of Cu in animal feed can lead to animal poisoning and Cu accumulation in animal products. Such overuse not only harms the health of livestock but can also affect public health.
Subject(s)
Animal Feed/adverse effects , Copper/toxicity , Food Safety , Intestines/pathology , Animals , China , Female , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestines/drug effects , Male , Mice , Mice, Inbred BALB C , Random Allocation , Sus scrofaABSTRACT
The effects of ethanol treatment on quality characteristics of cherry tomatoes were investigated over 11â¯days of storage at room temperature (25⯰C). Results showed that sensory quality was improved after ethanol treatment, with redder, softer fruits at the edible stage (11â¯days) compared with control fruit. In addition, the contents of ascorbic acid, sucrose and fructose were elevated after ethanol treatment as well as the concentration of 6-methyl-5-hepten-2-one. Conversely, decreased levels of methyl salicylate (MeSA), guaiacol, (Z)-3-hexenal and (E)-2-hexenal were observed. Selected consumers showed a preference for ethanol-treated cherry tomato fruits compared with controls. Taken together, 0.1% ethanol application has the potential to improve the quality characteristics of cherry tomatoes stored at room temperature.
Subject(s)
Ethanol/pharmacology , Solanum lycopersicum/drug effects , Aldehydes/chemistry , Ascorbic Acid/analysis , Chromatography, High Pressure Liquid , Discriminant Analysis , Flavoring Agents/analysis , Fruit/chemistry , Fruit/drug effects , Fruit/metabolism , Humans , Least-Squares Analysis , Solanum lycopersicum/chemistry , Solanum lycopersicum/metabolism , Salicylates/chemistry , Sugars/analysis , Temperature , Volatile Organic Compounds/analysis , Volatile Organic Compounds/isolation & purificationABSTRACT
Effects of postharvest methyl jasmonate (MeJA) treatment on the contents of ascorbic acid and carotenoids, as well as the compositions and contents of volatile organic compounds (VOCs) in cherry tomato fruits were investigated during 11â¯days of storage at room temperature (25⯰C). The results showed that MeJA treatment significantly increased the contents of ascorbic acid and carotenoids, especially lycopene in postharvest cherry tomato fruits. Moreover, MeJA treatment improved the contents of carotenoids derived VOCs such as 6-methyl-5-hepten-2-one (MHO), while had no effect on firmness, sugars and titratable acidity. All above results suggested that the exogenous MeJA application is potential in enhancement of main health-promoting components and VOCs in postharvest cherry tomato fruits.