Platycodin-D exerts its anti-cancer effect by promoting c-Myc protein ubiquitination and degradation in gastric cancer.

Platycodin D (PD) is a triterpene saponin extracted from the root of Platycodon grandiflorum. It has been reported to exhibit multiple pharmacological and biological properties. There is substantial evidence to support that PD displays a wide range of anti-tumor activities. However, the detailed molecular mechanism still needs further elaboration. In the present study, to explore whether PD inhibits gastric cancer (GC) cell viability, eight GC cell lines and the GES-1 cell line (a gastric mucosal cell line) were tested. We found that PD exhibited better inhibitory activity on GC cell lines than on the non-tumor cell line. Besides, treatment with PD led to a significant cell cycle arrest, thereby causing subsequent apoptosis. Regarding the cell growth inhibition mechanism, PD can downregulate the protein level of c-Myc rather than its mRNA level in a dose-dependent manner. Further studies revealed that PD disturbed the overall ubiquitination level in GC cell lines and enhanced the ubiquitination-dependent degradation of c-Myc. Interestingly, the inhibition of cell viability by PD could be restored to a certain extent when the expression of c-Myc was recovered, suggesting that PD-mediated GC cell growth inhibition is closely associated with c-Myc expression. Our study proposes a novel molecular mechanism for PD inhibiting GC cell proliferation and growth by destabilizing the c-Myc protein. This work may lay a preliminary foundation for developing PD as an anti-cancer therapy.

Acceptance and needs of medication literacy education among children by their caregivers: A multicenter study in mainland China.

Background: This study aims to investigate the needs of child caregivers for popular science about safe medication for children, to deeply explore the characteristics of child caregivers' demand for safe medication and the shortcomings of current popular science work, and then to seek better coping strategies to ensure children's safe medication. Methods: A questionnaire was designed based on Lasswell's "5W" communication model to investigate the needs of child caregivers in terms of content, channels, and forms of popular healthcare science on the safe usage of children's medication. Results: The primary ways caregivers receive popular healthcare science education concerning safe medication usage knowledge are through medical institutions, notification by medical staff, and personal media. The caregivers of children have a high demand for the presentation of text, pictures, and videos in three forms of popular healthcare science content. Caregivers placed significant importance on the popularization of safe medication usage for children. The survey results showed that the top 3 ways for caregivers to think that the quality of popular healthcare science content was "very good" came from medical institutions, medical staff notifications, and personal media, effectively increasing popular healthcare information accuracy. The intelligibility and pertinence of content expression are urgently needed within the caregiver population. Conclusion: Caregivers are very concerned about the popular science of safe medication for children, and are willing to learn about relevant content. Guided by the demand, we should actively disseminate accurate and easy-to-understand popular science about safe medication for children to caregivers through online or offline channels so as to promote safe medication for children.

Differentiation of aggressive from non-aggressive pancreatic solid pseudopapillary neoplasms using computed tomography.

PURPOSES: Microscopic aggressive behaviors may be related with the prognosis of solid pseudopapillary neoplasms (SPNs). In this study, we investigate computed tomography (CT) features and differential diagnosis of aggressive and non-aggressive SPNs in pancreas. MATERIALS AND METHODS: 122 patients with pathologically proven SPNs in pancreas were included. Patients' age, tumor site, texture, shape, margins, exophytic growth, capsule, calcification, hemorrhage, pancreatic duct dilatation or pancreatic parenchyma atrophy, peripancreatic infiltration or metastases, vascular encasement, and enhancement pattern were assessed. The diagnostic accuracy was analyzed by using the receiver operating characteristic curve (ROC). RESULTS: There were 30 aggressive SPNs and 92 non-aggressive SPNs. Aggressive SPNs showed significantly higher frequencies of an ill-defined margin, patient age > 40.5 years, and tumor size < 42.1 mm, but lower frequencies of complete capsule, hemorrhage compared with non-aggressive SPNs (p < 0.05). Lack of complete capsule and age > 40.5 years were independent risk factors of aggressive SPNs (odd ratio 7.08 and 3.1, respectively). When we applied the two predictors in the logistic regression model, the area under the curve (AUC) was 0.77 with sensitivity of 86.7% and specificity of 55.4%. CONCLUSION: Size less than 42.1 mm, lack of complete capsule, ill-defined, and absent bleeding are useful CT imaging features for predicating aggressive SPNs. Patient age > 40.5 years and lack of complete capsule showed acceptable diagnostic performance for discriminating aggressive from non-aggressive SPNs.

Differentiation of hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinoma using contrast-enhanced computed tomography.

Hypovascular pancreatic neuroendocrine tumors (hypo-PNETs) are often misdiagnosed as pancreatic ductal adenocarcinoma (PDAC). However, the treatment options and prognosis of PNETs and PDAC are substantially different. This retrospective study differentiated hypo-PNETs from PDAC using contrast-enhanced CT (CE-CT). Clinical data and CE-CT findings, including tumor location, size, boundary, pancreatic duct dilatation, local invasion or metastases, tumor contrast enhancement, and tumor-to-pancreas enhancement ratio, were compared between 39 PDACs and 18 hypo-PNETs. At CT imaging, hypo-PNETs showed a higher frequency of a well-defined margin and lower frequencies of pancreatic duct dilatation and local invasion or metastasis when compared with PDAC (p < 0.05 for all). The mean attenuation of hypo-PNETs at the arterial and portal venous phase was significantly higher than that of PDAC (p < 0.001, p = 0.003, respectively). Similar results were observed in tumor-to-pancreas enhancement ratio. Tumor attenuation and tumor-to-pancreas enhancement ratio at the arterial phase showed the largest area under the curve (AUC) of 0.888 and 0.812 with 83.3-88.9% of sensitivity and 61.6-77.0% of specificity. Pancreatic duct dilatation, local invasion or metastasis, and tumor attenuation at the portal venous phase also showed acceptable AUC (0.703-0.748). Thus CE-CT features, especially the enhancement degree at the arterial phases, may be useful for differentiating hypo-PNETs from PDAC using CE-CT.

The differentiation of pancreatic neuroendocrine carcinoma from pancreatic ductal adenocarcinoma: the values of CT imaging features and texture analysis.

BACKGROUND: Imaging findings for pancreatic neuroendocrine carcinoma (PNEC) and pancreatic ductal adenocarcinoma (PDAC) often overlap. The aim of this study was to demonstrate the value of computed tomography (CT) imaging features and texture analysis to differentiate PNEC from PDAC. METHODS: Twenty-eight patients with pathologically-proved PDAC and 14 patients with PNEC were included in this study. CT imaging findings, including tumor boundary, size, enhancement degree, duct dilatation and parenchymal atrophy were used to compare PDAC and PNEC. CT texture features were extracted from CT images at the arterial and portal phases. RESULTS: More PNEC than PDAC had well-defined margins (57.1% vs 25.0%, p = 0.04). Parenchymal atrophy was more common in PDAC than in PNEC (67.9% vs 28.1%, p = 0.02). CT attenuation values (HU) and contrast ratios of PNEC inthe arterial and portal phases were higher than those of PDAC (p < 0.05 or 0.01). Entropy was lower and uniformity was higher in PNEC compare to PDAC at the arterial phase (p < 0.05). Contrast ratio showed the highest area under curve (AUC) for differentiating PNEC from PDAC (AUC = 0.98-0.99). Entropy and uniformity also showed an acceptable AUC (0.71-0.72). CONCLUSIONS: Our data indicate that CT imaging features, including tumor margin, enhanced degree and parenchymal atrophy, as well as texture parameters can aid in the differentiation of PNEC from PDAC.

Design, synthesis, and biological characterization of tamibarotene analogs as anticancer agents.

In our efforts of developing novel compounds as potential anticancer agents, a series of tamibarotene analogs containing Zn(2+) -binding moieties were designed and developed. Biological characterization identified compound 7b as the most potent one with improved antiproliferative activities against multiple cancer cell lines, compared to parent compound tamibarotene. Further characterization also demonstrated that compound 7b exhibited moderate activities as a histone deacetylase inhibitor with IC50 of 1.8 ± 0.1 µm, thus suggesting that this could contribute to the improved antiproliferative activities of 7b. Pharmacokinetic studies revealed that compound 7b could release tamibarotene after administration and prolong the circulation time of tamibarotene, and this may also potentially contribute to the improved antiproliferative activities. Collectively, the results demonstrated that compound 7b could serve as a new lead for further development of more potent analogs as potential anticancer agents.

Liposome encapsulated of temozolomide for the treatment of glioma tumor: preparation, characterization and evaluation.

Temozolomide plays a critical role in curing glioma at present. The purpose of this work was to develop a suitable drug delivery system which could prolong the half-life, improve the brain targeting, and reduce the systemic effect of the drug. Temozolomide-liposomes were formulated by the method of proliposomes. They were found to be relatively uniform in size of 156.70 ± 11.40 nm with a narrow polydispersity index (PI) of 0.29 ± 0.04. The average drug entrapment efficiency and loading capacity were 35.45 ± 1.48% and 2.81 ± 0.20%, respectively. The pH of temozolomide-liposomes was 6.46. In vitro release studies were conducted by a dynamic dialysis. The results showed that temozolomide released slowly from liposomes compared with the solution group. The release behavior of temozolomide-liposomes was in line with First-order kinetics and Weibull equation. The pharmacokinetics study was evaluated by pharmacokinetics parameters. The t(1/2ß) and MRT of temozolomide-liposomes were 3.57 times and 1.27 times greater than that of temozolomide solution. The Cmax and AUC values of temozolomide-liposomes were 1.10 times and 1.55 times greater than that of temozolomide solution. The results of pharmacokinetics study showed temozolomide-liposomes prolonged the in vivo circulation time and increased AUC. Furthermore, the biodistribution in mice showed that temozolomide-liposomes preferentially decreased the accumulation of temozolomide in heart and lung and increased the drug concentration in brain after i.v. injection, which implied that temozolomide-liposomes improved the therapeutic effect in the brain and reduced the toxicity in lung and heart.

Development of etoposide-loaded bovine serum albumin nanosuspensions for parenteral delivery.

Nanosuspensions emerge as a promising strategy for delivery of poorly water-soluble drugs. Albumin is a versatile protein carrier for drug delivery and targeting. The purpose of this study was to develop a formulation of etoposide-loaded bovine serum albumin (BSA) nanosuspensions, to study in vitro characterization, and to estimate the in vivo safety and tissue distribution of etoposide-loaded BSA nanosuspensions for parenteral delivery. Etoposide-loaded BSA nanosuspensions were prepared by high-pressure homogenization-solvent precipitation method. The particle size, zeta potential, drug entrapment efficiency, and drug loading of the lyophilized formulation were 182.3 nm, -22.18 mV, 86.44%, and 8.49% respectively. In vitro release files of the formulation presented sustained release properties. Preliminary safety study was conducted to evaluate the delivery system, and results indicated that myelosuppression effect of the etoposide-loaded BSA nanosuspensions group was significantly lower than the Injection® group. Furthermore, results of tissue distribution studies showed that the concentration and AUC of etoposide were increased significantly in lung, liver, spleen while reduced in heart, kidney compared with the etoposide injection® group after i.v. administration of etoposide-loaded BSA nanosuspensions. The formulation played a role in targeting delivery to lung, reduce toxicity, and side effects of etoposide. In conclusion, etoposide-loaded BSA nanosuspensions were promising for parenteral delivery of etoposide.

Novel PEG-grafted nanostructured lipid carrier for systematic delivery of a poorly soluble anti-leukemia agent Tamibarotene: characterization and evaluation.

Tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL), loaded nanostructured lipid carrier (Am80-NLC) was developed and characterized previously. The purpose of the present work was to develop PEGylated nanostructured lipid carrier (PEG-NLC) for intravenous delivery of Am80, with the aim to further extend the circulation in blood and decrease the adverse events. Am80-loaded PEG-NLC (Am80-PEG-NLC) modified with PEG-40 stearate (PEG40-SA, molecular weight 2000 Da) was formulated by the method of melt-emulsification and low temperature-solidification technique. Am80-NLC was developed as well as control. Based on the optimized results of single-factor screening experiment, the average drug entrapment efficiency, the mean particle size, and zeta potential of Am80-NLC and Am80-PEG-NLC were found to be 89.8-94.3%, 178.9-201.6 nm, and -37.74 to -20.1 mV, respectively. In vitro drug release of Am80-NLC and Am80-PEG-NLC possessed a sustained release characteristic and their release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous (i.v.) injection to rats, the mean residence time (MRT) of Am80-PEG-NLC group was significantly prolonged and the AUC value was improved as well compared with the Am80-NLC group. Furthermore, the biodistribution in mice showed that Am80-PEG-NLC preferentially decreased the accumulation of Am80 in kidney and increased the drug concentration in brain after i.v. injection. In conclusion, Am80-PEG-NLC may be a potential delivery system for Am80 in the treatment of APL.

A novel approach for systematic delivery of a hydrophobic anti-leukemia agent tamibarotene mediated by nanostructured lipid carrier.

The present work evaluated the feasibility of nanostructured lipid carriers (NLC) for the intravenous delivery of tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL). The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects. The tamibarotene-loaded-NLC (Am80-NLC) nanosuspension was formulated by the method of melt-emulsification at a high temperature and solidified by ice bath. Based on the optimized results of single-factor screening experiment, the Am80-NLC was found to be relatively uniform in size (189.38+/- 8.07 nm) with a narrow poly-dispersity index (PI) (0.27+/-0.02) and a negative zeta potential (-34.69+/-3.05 mV). The average drug entrapment efficiency and loading capacity was 90.85+/- 1.03% and 9.08+/- 0.10%, respectively. The differential scanning calorimetry (DSC) analysis indicated that Am80 was not in crystalline state in Am80-NLC. The in vitro release profile of Am80-NLC possessed a sustained release characteristic and the release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous injection to mice, Am80-NLC showed a longer retention time and higher AUC values compared with the Am80 solution. In addition, biodistribution results clearly demonstrated that Am80-NLC preferentially decreased the drug distribution in kidney and liver of mice after intravenous injection. These results revealed that injectable Am80-NLC may serve as a promising carrier for Am80 to increase therapeutic efficacy on APL and reduce adverse events.

[Intestinal absorption of enteric coating potassium sodium dehydroandroan drographolide succinate pellets in rat and in vivo pharmacokinetics study].

OBJECTIVE: To develop a method for determination the content of Potassium Sodium Dehydroandroan drographolide Succinate (PSDS) in rat intestinal contents and plasma and investigate the intestinal absorption of PSDS pellets in rat and in vivo pharmacokinetics of PSDS pellets. METHODS: The content of PSDS in rat intestinal contents and plasma was determined by HPLC. In vivo pharmacokinetic properties and intestinal absorption of PSDS pellets in rat were investigated. RESULTS: Two hours after administration, pellets were not found in the small intestine and large intestine, four hours after administration, the largest number of pellets were found in the small intestine and the concentration of PSDS was the highest in the intestinal contents (3593.13 microg). The characteristics of plasma concentration-time curve was consistent with a single compartment model. The main drug pharmacokinetic parameters were calculated. t1/2, T(max), C(max) and AUC were 2.69 h, 5 h, 3.02 microg/mL and 6.42 microg x h/mL, respectively. CONCLUSION: PSDS has a good absorption in the rat small intestine and it is feasible to prepare PSDS enteric-coated pellets for oral administration.