Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells

Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.     

Renal vectorial transport of berberine mediated by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats

Berberine, a well‐known plant alkaloid derived from Rhizoma coptidis, has potential applications as a therapeutic drug for diabetic nephropathy. However, the transporter‐mediated renal transport of berberine remains largely unclear. This study aimed to investigate the renal transport mechanism of berberine using transfected cells, kidney slices and animal experiments. In Madin‐Darby canine kidney (MDCK) cells stably expressing rat OCT2 (MDCK‐rOCT2) and kidney slices, saturable and non‐saturable uptake of berberine was observed, and corticosterone could inhibit the uptake of berberine, with IC₅₀ values of 0.1 μm and 147.9 μm , respectively. In double‐transfected cells, the cellular accumulation of berberine into MDCK‐rOCT2 and MDCK‐rOCT2‐rMATE1 (MDCK cells stably expressing rOCT2 and rMATE1) cells was significantly higher than the uptake into MDCK cells. Meanwhile, berberine transcellular transport was considerably higher in double‐transfected MDCK‐rOCT2‐rMATE1 cells than in MDCK and MDCK‐rOCT2 cells. Corticosterone for MDCK‐rMATE1 and MDCK‐MDR1 and pyrimethamine for MDCK‐rMATE1 at high concentrations could inhibit the efflux of berberine. In animal experiments, compared with the berberine alone group, the cumulative urinary excretion of berberine significantly decreased in the corticosterone or pyrimethamine pretreatment groups. In the rat kidney, pyrimethamine increased, and a low dose of corticosterone (5 mg/kg) decreased, the berberine concentration. However, there was no apparent change in the renal concentration of berberine in rats pretreated with corticosterone (10 or 20 mg/kg). Thus, berberine is not only a substrate of OCT2 and P‐glycoprotein, but is also a substrate of MATE1. Both OCT2 and MATE1 mediate the renal vectorial transport of berberine.     

氨基糖苷类对禽肠道细菌的耐药判定标准研究进展

禽消化道细菌病是危害养禽业的主要问题之一,沙门菌病、大肠埃希菌病等家禽肠道细菌病的流行日趋复杂,越来越难以控制,且不断出现新的流行与致病特点,不仅会造成严重肠道疾病而且会产生死亡。氨基糖苷类抗生素是高效、广谱抗生素,在临床上广泛应用,但是养殖业用药的不合理导致细菌的氨基糖苷耐药性日趋严重,这在很大程度上降低了其临床应用的潜力。而耐药监测需要判定标准,目前我国并没有相关标准,主要参考美国临床和实验室标准化协会(CLSI)和欧盟抗菌药物敏感性试验委员会(EUCAST)中的折点。当前CLSI和欧盟EUCAST标准中氨基糖苷类抗生素对禽消化道细菌病折点的制定并不完全,所以要全面建立符合我国国情的流行病学临界值和药效学临界值,为折点的制定工作提供科学数据,以监测耐药性的产生,分析耐药现状和发展规律,更科学地指导临床用药和新药开发。     

2014-2016年六安市中医院医疗机构中药制剂的应用分析

目的：分析六安市中医院2014-2016年医疗机构中药制剂的使用情况,评价其存在的重要性,并对未来发展提出建议。方法：利用医院信息系统,分析2014-2016年我院中药制剂的使用情况。结果：2014-2016年我院中药制剂使用数量大,销售金额占一定比例,排名前五名的制剂分别为十味疏风通窍颗粒、归芍明目颗粒、十味利湿颗粒、芪归通络颗粒、扶正排毒颗粒,但是中药制剂在医院总药品中所占的比例较低,中药制剂使用量亟待提高。结论：医疗机构中药制剂仍有存在的必要性,为加强医院中药制剂的发展,应优化产业结构,加大对传统中药制剂的支持力度;核定制剂价格,提升中药制剂的院内地位;利用新技术研发新制剂,提高中药制剂研究水平;制剂纳入医保范围,提高中药制剂的使用率;转变思路,合理使用中药制剂。     

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

In the present study, we aimed to prepare poloxamer 403/407 mixed micelles in order to improve the solubility and oral bioavailability of genistein.Genistein was incorporated in the mixed poloxamer micelles by thin-film hydration method, and its physicochemical properties, including particle size, zeta potential, entrapment efficiency and drug loading, were investigated.In vitro release of genistein from the mixed micelles was monitored by dialysis method, and pharmacokinetic study of genistein loaded mixed micelles was carried out in rats. We found that the particle size and zeta potential of mixed micelles were (20.31±0.43) nm and (–8.94±0.35) mV, with encapsulation efficiency 90.59%±0.67% and drug loading 7.74%±0.05%. Solubility of genistein in mixed micelles reached 3.80 mg/mL, which was about 130 times higher than that in water.Genistein-loaded mixed micelles showed sustained release characteristics in vitro with no burst release phenomenon, but it was faster than suspension.The AUC_0–t andAUC_0–∞ of mixed micelles were 196.74% and 204.62% greater than that of genisein suspension, respectively.Consequently,poloxamer 403/407 mixed micelles significantly improved the solubility and oral bioavailability of genistein, which could be used as an effective drug delivery system for oral administration of poorly soluble drugs.     

三种乳腺癌化疗方案的药物经济学分析

目的 从药物经济学角度评价乳腺癌术后3种化疗方案的经济学效果,为临床合理用药提供参考。方法 90例乳腺癌术后患者分为3组(TAC、PEC、AC),采用药物经济学的成本-效果分析法对3种化疗方案进行临床病例的回顾性分析比较(T：多西他赛,A：多柔比星,C：环磷酰胺,P：紫杉醇脂质体,E：表柔比星)。结果 3组化疗方案的总体有效率分别为71.87%,73.07%,65.62%;治疗成本分别为11713.49元,18197.79元和7795.82元;成本-效果比分别为162.98,249.04,118.80。化疗不良反应方面,PEC组发生率高于TAC组及AC组,差异有显著性(P≤0.05)。结论 TAC为乳腺癌术后化疗较佳的治疗方案,值得推广。     

Association between dietary zinc intake and mortality among Chinese adults: findings from 10-year follow-up in the Jiangsu Nutrition Study

Purpose

Population studies of the association between zinc intake and mortality yield inconsistent findings. Using data from Jiangsu Nutrition Study, we aimed to assess the association between zinc intake and mortality among Chinese adults.

Methods

We prospectively studied 2832 adults aged 20 years and older with a mean follow-up of 9.8 years. At baseline, food intake was measured by 3-day weighed food record (WFR) between September and December in 2002. Death occurrence was assessed in 2012 during a household visit as well as by data linkage with the regional death registry. Hazard ratios (HRs) and 95% CI were calculated using competing risks regression (CVD and cancer mortality) and Cox proportional hazards analysis (all-cause mortality).

Results

During 27,742 person-years of follow-up, there were 184 deaths [63 cancer deaths and 70 cardiovascular disease (CVD) deaths]. Dietary zinc to energy ratio was positively associated with cancer and all-cause mortality. Across quartiles of the zinc to energy ratio from low to high, the HR (95% CI) for all-cause mortality was 1.00, 1.80 (95% CI 1.10–2.95), 1.55 (95% CI 0.96–2.50), and 1.85 (95% CI 1.11–3.07), respectively. Comparing the extreme quartiles of the zinc to energy ratio, the HR for cancer mortality was 2.28 (95% CI 1.03–5.04).

Conclusion

Zinc intake was positively related to all-cause mortality and cancer mortality.

     

Cefquinome-loaded microsphere formulations against Klebsiella pneumonia infection during experimental infections

The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7?mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8?±?3.6?μm). The encapsulation efficiency and drug loading of cefquinome were 91.6?±?2.6% and 18.7?±?1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1β and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.