ABSTRACT
@#Population bioequivalence (PBE) is a statistical approach recommended by FDA to evaluate the consistency of particle size distribution of numerous nanoparticle products.However, when particle size distribution (PSD) profile exhibits multiple peaks or other complex distributions, the traditional descriptors D50 and SPAN are no longer suitable to describe PSD.Earth mover''s distance (EMD) is a new statistical metric for assessing the difference between distributions.In this study, we used EMD to measure the discrepancy between PSD and then PBE was applied to perform statistical test to establish equivalence.Our results showed that the proposed method can effectively reject an unequivalent product and pass an equivalent product, thus indicating its helpfulness in guiding the optimization of formulation and preparation process.
ABSTRACT
OBJECTIVE@#To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms.@*METHODS@#Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, =5)or normal saline (control group, =5) for 24 d. Tumor weight and body weight were calculated.@*RESULTS@# experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all <0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all <0.05); and the secretion of lactic acid was also markedly reduced (all <0.05). experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (<0.05), but no difference in body weights between two groups was observed.@*CONCLUSIONS@#High dose VC may inhibit proliferation of breast cancer cells both and through reducing glycolysis and protein synthesis.
Subject(s)
Animals , Humans , Mice , Ascorbic Acid , Pharmacology , Breast Neoplasms , Drug Therapy , Cell Line, Tumor , Cell Proliferation , Glycolysis , Mice, Nude , Protein BiosynthesisABSTRACT
OBJECTIVE@#To investigate the effects of Honokiol on cognitive function in mice with epilepsy.@*METHODS@#Kainic acid (38 mg/kg) was intraperitoneally injected in 5 weeks old male ICR mice to induce epilepsy. Honokiol at dose of 3, 10, 30 mg/kg was given to epilepic mice by intraperitoneal injection for 10 days. Fluoro-Jade B staining was used to assess neuronal death; Morris water maze and Y maze tests were used to measure cognitive function such as learning and memory; Western blot was performed to detect the expression of acetylated superoxide dismutase (SOD), microtubule associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and P62 in hippocampus tissue; thiobarbituric acid and WST-1 methods were used to detect malondialdehyde (MDA) and SOD.@*RESULTS@#Compared with control group, the levels of acetylated-SOD, MDA, LC3-Ⅱ, P62 and neuronal death increased, cognitive function and SOD decreased in model group (<0.05 or <0.01). Honokiol at the dose of 10 mg/kg and 30 mg/kg decreased SOD acetylation, MDA content, expression of LC3-Ⅱ and P62, as well as neuronal death, and the cognitive function was improved (<0.05 or <0.01), especially in 30 mg/kg Honokiol group.@*CONCLUSIONS@#Honokiol alleviates oxidative stress and autophagy degradation disorder, decreases neuronal death, and therefore improves cognitive function in epilepsy mice.