Coordinate Bonding Strategy for Molecularly Imprinted Hydrogels: Toward pH-Responsive Doxorubicin Delivery

Molecularly imprinted hydrogel (MIH) as drug delivery system has been studied. It still remains a challenge to construct the stimuli-responsive MIH. Here, we report a coordinate bond strategy for imprinting doxorubicin (Dox) in hydrogel capable of pH-responsive and sustained drug delivery. The imprinting condition such as template–monomer interactions induced by metal ion was carefully investigated by spectroscopic methods. The obtained Dox–MIH was evaluated by absorption and in vitro release experiments. It has been demonstrated that the cupric ion mediated interaction between Dox and 4-vinyl pyridine via coordination and the optimal coordinate ratio of Dox/Cu²⁺ was 2:1. The rebinding amount of MIH to Dox was 2.7-fold that of nonimprinted hydrogel and the Dox-loaded MIH showed a pH-responsive release property. Not more than 10% of loaded drug was released from Dox–MIH at pH 7.2 during a time course of 7 days. However, near to 60% of loaded drug was sustainedly released at pH 5.0 during the same period. These results indicated that Dox–MIH with pH-responsive behavior possessed great promising as sustained-release delivery system of anticancer drug.     

An Experimental Study on the Anti-Ehrlich Ascites Carcinoma Effect of Purified Toad Venom Extract

The objective of this paper was to study the anti-Ehrlich ascites carcinoma effect of purified toad venom extract and its mechanism. Mouse model of Ehrlich ascites carcinoma was established with cisplatin as the control to observe the inhibitory effect of purified toad venom extract on malignant peritoneal effusion in mice. The results showed that compared with the control group, ascites volume, number of tumour cells and tumour cell viability decreased and ascites inhibition rate reached over 50% in each treatment group, and with the increase of the dose, incidence of ascites showed a downward trend. The number of tumour cells in ascites and tumour cell viability in the purified toad venom high-dose group were lower than those of the cisplatin group. Compared with the model group, survival time was prolonged in varying degrees in the purified toad venom groups and cisplatin group. The study concluded that purified extract of toad venom has an anti-Ehrlich ascites carcinoma effect.     

Polymorphisms in arachidonic acid metabolism-related genes and the risk and prognosis of colorectal cancer

Cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LOX) and phospholipaseA2 (PLA2) played important roles in the modulation of apoptosis, angiogenesis, carcinogenesis and invasion of colorectal cancer (CRC). The polymorphisms in COX-2, 12-LOX and PLA2 may affect their roles. Therefore, we investigated if COX-2 ?1195G > A, 12-LOX 261Arg > Gln and PLA2 c.349 + 191A > G polymorphisms were associated with risk and prognosis of CRC as well as possible interactions with the environmental factors on the risk of CRC in Northeast of China. A case–control study with 451 cases and 631 controls were carried out, a cohort with 386 patients were followed up. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Compared with the 261Arg/Arg genotype, 12-LOX 261Arg/Gln genotype and 261Arg/Gln + Gln/Gln genotypes reduced the risk of rectal cancer by 33 % (adjusted OR = 0.67, 95 % CI 0.47–0.97, p = 0.03) and 32 % (adjusted OR = 0.68, 95 % CI 0.49–0.96, p = 0.03), respectively. The adjusted HR for the association between 12-LOX 261Gln/Gln genotype and overall survival in patients with CRC was 1.68 (95 % CI 1.06–2.68, p = 0.03). There was also evidence of an interaction between the PLA2 c.349 + 191 A > G genotypes and the overnight food consumption (adjusted OR_i = 1.92, 95 % CI 1.14–3.25, P _interaction = 0.01). These observations indicate that 12-LOX 261Arg > Gln polymorphism may affect risk of rectal cancer, and it may be a potential predictive marker for prognosis of CRC.     

In vitro assessment of cytotoxicity and labeling efficiency of 99mTc-HMPAO with stromal vascular fraction of adipose tissue

IntroductionNoninvasive radionuclide imaging of cells using technetium99m-hexamethylpropyleneamine oxime (^99mTc-HMPAO) is a potential diagnostic tool for several applications. Herein we aimed to evaluate the labeling efficiency and cellular toxicity of ^99mTc-HMPAO with Stromal Vascular Fraction (SVF) of adipose tissue to develop a process tool for theranostic purposes, in particular imaging cardiac stem cell therapy.MethodsTen million cells of SVF were labeled with ^99mTc-HMPAO complex and excess radiolabel was cleared off through washing in PBS. The labeling efficiency of ^99mTc-HMPAO was detected in labeled cells and their subsequent supernatant wash using isotope dose calibrator and gamma camera. The cytotoxicity was assessed for the comparative reactive oxygen species (ROS) by H₂DCFDDA, apoptotic events by annexin-V and TUNEL assay and mitochondrial potential by JC-1.ResultsAn encouraging labeling efficiency of 33% was observed with ^99mTc-HMPAO complex. The radionuclide labeling of SVF demonstrated significant safety profile as evaluated by apoptotic assays.Conclusion^99mTc-HMPAO labeling efficiency of 33% of total SV fraction would produce sufficient radioactive signals that would enable for in vivo tracking of cells by SPECT-CT. The radionuclide did not demonstrate any significant impact on the structural or functional organization of the labeled cells. Our study indicates that SVF can be safely labeled with ^99mTc-HMPAO without adverse cytotoxic events and for its potential role in imaging cardiac stem cell therapy.     

生髓健骨胶囊对酒精性骨质疏松大鼠骨密度、骨矿含量影响的研究

目的从基因分子水平探讨酒精性骨质疏松(alcoholic osteoporosis,AOP)大鼠的发病机制,观察生髓健骨胶囊对AOP大鼠骨密度(bone mineral density,BMD)、骨矿含量(bone mineral content,BMC)表达的影响,探讨生髓健骨胶囊对AOP大鼠模型的中药防治作用机理。方法选取成年雄性(清洁级)SD大鼠120只,称体重,随机分为4组,每组各30只,用白酒灌胃法造模,同时分别给予生理盐水、碳酸钙阿法D3、生髓健骨胶囊灌胃给药。于造模8、12、16周末取材,检测股骨上端BMD、BMC指标。结果检测造模干预8、12、16周后BMD、BMC指标变化,模型组BMD、BMC与正常组比较明显降低,且差异有统计学意义(P0.01),结果表明饮酒大鼠确实存在骨量减少,BMD、BMC降低;中药干预组BMD、BMC与模型组相比显著升高(P0.01);中药干预组BMD、BMC与西药对照组相比,明显升高(P0.05)。结论通过观察生髓健骨胶囊对AOP大鼠的实验指标,证明了生髓健骨胶囊能够提高AOP大鼠骨密度,增加骨矿含量,抑制矿物质丢失,改善大鼠的骨代谢。     

Laparoscopic versus open pancreatoduodenectomy: an individual participant data meta-analysis of randomized controlled trials

BackgroundRandomized trials have compared laparoscopic pancreatoduodenectomy (LPD) to open pancreatoduodenectomy (OPD) with conflicting results. An IPDMA may give more insight into the differences between LPD and OPD, and could identify high-risk subgroups.MethodsA systematic literature search was performed in the Pubmed, Embase, and the Cochrane library databases (October 2019). Out of 1410 studies, three randomized trials were identified. Primary outcome was major complications (Clavien-Dindo grade ≥ III). Subgroup analyses were performed for high-risk subgroups including patients with BMI of ≥25 kg/m2, pancreatic duct <3 mm, age ≥70 years, and malignancy.ResultsData from 224 patients were collected. After LPD, major complications occurred in 33/114 (29%) patients compared to 34/110 (31%) patients after OPD (adjusted odds ratio (OR) 0.62; 95% confidence interval (CI) 0.3–1.4, P = 0.257). No differences were seen for major complications and 90-day mortality LPD 8 (7%) vs OPD 4 (4%) (adjusted OR 0.2; 95% CI 0.02–1.3, P = 0.080). With LPD, operative time was longer (420 vs 318 min, p < 0.001) and hospital stay was shorter (mean difference ?6.97 days). Outcomes remained stable in the high-risk subgroups.ConclusionLPD did not reduce the rate of major postoperative complications as compared to OPD. LPD increased operative time and shortened hospital stay with 7 days.