Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

[Correlation of Serum Concentration of Nilotinib with Clinical Efficacy in Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients. METHODS: A total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry. RESULTS: Median Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)]. CONCLUSION: Cmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.

Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells.

Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor Î³ (PPARγ)/liver X receptor α (LXRα) in THP­1 macrophage-derived foam cells. THP­1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP­1 macrophage-derived foam cells.

[An experimental study on cardiopulmonary resuscitation by cardiac massage under diaphragmatic muscle for rabbit with cardiac arrest].

OBJECTIVE: To compare the hemodynamic effect of standard-cardiopulmonary resuscitation (S-CPR) and of CPR by cardiac massage under the diaphragmatic muscle (D-CPR), and to evaluate the feasibility of D-CPR. METHODS: Twenty healthy New Zealand rabbits were randomly divided into two groups: one group receiving S-CPR (n=10) and the other group receiving D-CPR (n=10). Cardiac arrest was induced by asphyxiation at the end expiration for 8 minutes. After the hemodynamic situation was stable for 5 minutes before asphyxiation, the readings of ascending aorta systolic pressure (AOS) and diastolic pressure (AOD), transcutaneous oxygen saturation (SpO(2)), right atrial systolic pressure (RASP), right atrial diastolic pressure (RADP), and electrocardiogram were recorded consecutively to the end of the experiment . The mean arterial pressure (MAP) of ascending aorta and coronary perfusion pressure (CPP) were calculated. The rate of restoration of spontaneous circulation (ROSC) and the survival rate in a short duration of 6 hours were observed. RESULTS: Five rabbits in S-CPR group and 8 in D-CPR group were successfully resuscitated and obtained ROSC (50%, 80%, P=20.05). Six hours survival rate was 40% in S-CRP group and 50% in D-CPR group. The comparisons between the two groups on AOS, AOD, MAP and CPP respectively showed that at 1 minute and 5 minutes during resuscitation the respective variables were higher in the D-CPR group than that in the S-CPR group (all P<0.05). Compared to the hemodynamics before asphyxiation, the MAP and CPP in the D-CPR group increased 54.1% and 33.4% of basic value at 1 minute, and they were 60.0% and 41.8% at 5 minutes, while the AOS and AOD in the S-CPR group only increased by an average of 37.3% and 16.5% at 1 minute, and they were 38.5% and 17.1% at 5 minutes, respectively. After ROSC, the hemodynamic variations of the D-CPR rabbits were more stable than those of S-CPR rabbits. CONCLUSION: D-CPR can provide higher arterial pressure, cardiac output, rate of ROSC and survival rate in a short period than S-CPR can induce, so that D-CPR is superior to S-CPR.