Purpose: Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin have been hampered by its extreme water insolubility. To overcome this limitation, this study is aimed to develop liposomal quercetin and investigate its distribution in vivo and antitumor efficacy in vivo and in vitro. Experimental Design: Quercetin was encapsulated in polyethylene glycol 4000 liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg in tumor-bearing mice was detected by high-performance liquid chromatography. Induction of apoptosis by liposomal quercetin in vitro was tested.The antitumor activity of liposomal quercetin was evaluated in the immunocompetent C57BL/6N mice bearing LL/2 Lewis lung cancer and in BALB/c mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and survival time were observed. The mechanisms underlying the antitumor effect of quercetin in vivo was investigated by detecting the microvessel density, apoptosis, and heat shock protein 70 expression in tumor tissues. Results: Liposomal quercetin could be dissolved in i.v. injection and effectively accumulate in tumor tissues. The half-time of liposomal quercetin was 2 hours in plasma. The liposomal quercetin induced apoptosis in vitro and significantly inhibited tumor growth in vivo in a dosedependent manner. The optimal dose of liposomal quercetin resulted in a 40-day survival rate of 40%. Quantitative real-time PCR showed that liposomal quercetin down-regulated the expression of heat shock protein 70 in tumor tissues. Immunohistochemistry analysis showed that liposomal quercetin inhibited tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis. Conclusions: Our data indicated that pegylated liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be a potential application in the treatment of tumor.
Background: Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon.
BackgroundThere has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs).MethodsA quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis.ResultsSignificant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67–0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50–0.76); p < 0.0001), and number of hospital admissions per 100 ED presentations (0.61 (0.43–0.85); p = 0.004) were noticed in the experimental hospital after the intervention; while there were no significant differences between intervention and control hospitals before the intervention. Pre-test and post-test comparison in the intervention hospital also presented significant decreases in ED presentation rate (0.75 (0.65–0.86); p < 0.0001) and hospital admission rate per RACF bed (0.66 (0.54–0.79); p < 0.0001), and a non-significant reduction in hospital admission rate per ED presentation (0.82 (0.61–1.11); p = 0.196).ConclusionsHospital in the Nursing Home program could be effective in reducing ED presentations and hospital admissions from RACF residents. Implementation of the program across a variety of settings is preferred to fully assess the ongoing benefits for patients and any possible cost-savings.
Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.
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Brain functional network properties are globally disrupted in multiple musculoskeletal chronic pain conditions. Back pain with lumbar disk herniation (LDH) is highly prevalent and a major route for progression to chronic back pain. However, brain functional network properties remain unknown in such patients. Here, we examined resting-state functional magnetic resonance imaging-based functional connectivity networks in chronic back pain patients with clear evidence for LDH (LDH-chronic pain n = 146), in comparison to healthy controls (HCs, n = 165). The study was conducted in China, thus providing the opportunity to also examine the influence of culture on brain functional reorganization with chronic pain. The data were equally subdivided into discovery and validation subgroups (n = 68 LDH-chronic pain and n = 68 HC, for each subgroup), and contrasted to an off-site data set (n = 272, NITRC 1000). Graph disruption indices derived from 3 network topological measurements, degree, clustering coefficient, and efficiency, which respectively represent network hubness, segregation, and integration, were significantly decreased compared with HC, across all predefined link densities, in both discovery and validation groups. However, global mean clustering coefficient and betweenness centrality were decreased in the discovery group and showed trend in the validation group. The relationship between pain and graph disruption indices was limited to males with high education. These results deviate somewhat from recent similar analysis for other musculoskeletal chronic pain conditions, yet we cannot determine whether the differences are due to types of pain or also to cultural differences between patients studied in China and the United States.
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