ABSTRACT
We observed the effect of calcium dobesilate (CaD) on apoptosis induced by cisplatin in human proximal tubular epithelial cells (HK-2) and explored the possible mechanism. Based on HK-2 cells apoptosis model induced by cisplatin, CCK-8 method was used to detect the effect of CaD on the proliferation of HK-2. Apoptosis was detected by flow cytometry. Reactive oxygen species (ROS) assay was used to evaluate the level of oxidative stress. The mitochondrial membrane potential was measured by JC-1 method. The expression levels of p53, caspase-3, bcl-2 and bax in cisplatin-induced HK-2 were detected by Western blot. The expression of renal injury factor 1(KIM-1) and neutrophil gelatin-related apolipoprotein (NGAL), markers of acute kidney injury, were detected by ELISA. The results showed that CaD could reduce the oxidative stress level induced by cisplatin and inhibit apoptosis in renal tubular epithelial cells. Cisplatin can up-regulate the protein expressions of p53, caspase-3, bax, KIM-1 and NGAL, and reduce the expression of bcl-2. After using CaD, the protein levels of KIM-1, NGAL, p53, caspase-3 and bax were significantly reduced, while the levels of bcl-2 were increased. This study has shown that CaD can alleviate cisplatin-induced HK-2 injury and inhibit HK-2 apoptosis, which may be related to the regulation of bax/bcl-2/caspase-3 apoptosis signaling pathway.
ABSTRACT
Objective To prepare the resveratrol-DPPC liposomal dry powder inhalations (RDLDPIs), and solve the problem of lower bioavailability of resveratrol after oral administration. Methods The RDLDPIs were prepared by film-dispersion and freeze drying. The formulation was optimized by orthogonal design. The particle size, entrapment efficiency, electric potential, in vitro release, and lung deposition were characterized. The broth microdilution method was used to evaluate the antibacterial activity and determine the minimal inhibitory concentration (MIC) in vitro. Results The optimized ratio of DPPC/cholesterol, resveratrol/DPPC, and mannitol/DPPC was 3:1, 1:3, and 2:1 in the prescription of RDLDPIs, respectively; And hydration time was 15 min. The entrapment efficiency of RDLDPIs was (69.8 ± 1.6)%, the drug loading was (2.4 ± 0.9)%, the particle size was (191.5 ± 4.5) nm, and the zeta potential was (12.4 ± 1.5) mV. The aerodynamic particle size of the powder was (3.2 ± 0.2) μm and the in vitro pulmonary deposition ratio was 28.1% in vitro. The antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Streptococcus pneumoniae, and Pseudomonas aeruginosa was evaluated in vitro. The crude drug group had no antibacterial activity in four species of bacteria, while RDLDPIs had antibacterial activity of Staphylococcus aureus and Acinetobacter baumannii, and MIC was 4 mg/mL and 2 mg/mL, respectively. Conclusion The prepared RDLDPIs have small size and uniform distribution with good stability and high lung deposition rate and in vitro antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, which is expected to be an substitute for traditional antibiotics for the treatment of bacterial pneumonia.
ABSTRACT
Objective·To analyze the clinical features and prognostic factors of desmoplastic small round cell tumor (DSRCT). Methods·Clinical datum of 140 patients with DSRCT published from Nov. 2003 to Jul. 2012 were collected and studied retrospectively by searching Medline and Embase databases. The observation indicators were progression-free survival (PFS) or overall survival (OS). Survival rates were calculated using the Kaplan-Meier method and compared between groups using a log-rank test. Multivariate analysis was performed using the Cox model to determine the prognostic factors. Results·Patient median age was (23.2±12.7) years (range 4-74 years, the ratio of male and female was 3.12:1). Frequent symptoms were abdominal pain (35.7%) and evidence of a palpable mass (20.0%). 106 cases tumors were in the abdominal or pelvic cavity, the remaining were extra-abdominal tumors. The frequency of patients receiving conventional chemotherapy, cytoreductive surgery, neoadjuvant chemotherapy, adjuvant chemotherapy or first-line chemotherapy was 76.4%, 52.1%, 17.1%, 47.9% and 38.6%, respectively. Some patients received adjuvant radiotherapy (17.1%), hyperthermic intraperitoneal chemotherapy (4.1%) and bone marrow transplantation (7.3%). By univariate analysis, male gender, absence of metastasis, effective cytoreductive surgery, chemotherapy and multimodal therapy were significant prognostic factors for prolonged OS (all P<0.05). Primary tumor site, extra-abdominal tumors, absence of metastasis and effective cytoreductive surgery were associated with improved PFS (all P<0.05). Cox regression analysis showed effective cytoreductive surgery and chemotherapy were independent prognostic factors. Conclusion·Multimodal therapeutics that clear tumors by surgery, adjuvant therapy are favorable prognostic factors for improved survival level in DSRCT patients.