Q39, a novel synthetic Quinoxaline 1,4-Di-N-oxide compound with anti-cancer activity in hypoxia

Hypoxia is one of the inevitable circumstances in various tumors and results in tumor resistance to radiotherapy and chemotherapy. The present data showed that 3-(4-bromophenyl)-2-(ethylsulfonyl)-6-methylquinoxaline 1,4-dioxide (Q39), derived from Quinoxaline 1,4-Di-N-oxide, possessed high anti-cancer activity in hypoxia. Cytotoxicity assay demonstrated that Q39 is a potential and high efficient anti-cancer compound in all tested cell lines with IC50 values of 0.18+/-0.03-8.88+/-1.12 microM in hypoxia and 0.33+/-0.04-8.74+/-1.28 microM in normoxia . In the following work concerning the mechanism of Q39 in hypoxia, we confirmed that Q39 could cause the apoptosis of K562 cells in a time-dependent manner. By fluorescence stain assay, Q39-induced mitochondria membrane potential (Delta Psi m) loss was observed in K562 cells in hypoxia. Based on the western blotting, Q39 decreased the protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in hypoxia. The compound caused the activation of caspase-3 and subsequent cleavage of its substrate poly (ADP-ribose) polymerase (PARP) in hypoxia. Meanwhile, we found the upregulation of Bax by Q39 in K562 cells as well as the downregulation of Bcl-2. Q39 also influenced the expression of Mitogen-Activated Protein Kinase (MAPKs) and other proteins relative to mitochondria induced apoptosis. In addition, Q39-mediated apoptosis was not reversed after treatment with the JNK-specific inhibitor. In summary, the present study demonstrated Q39 was a novel compound against cancer cells in hypoxia. The mitochondrial pathway mediated by Bcl-2 protein family and MAPKs and the HIF-1 pathway might be involved in signaling Q39-induced apoptosis.     

宫颈癌放化疗患者心理健康现状分析与对策

目的 了解宫颈癌放化疗患者心理健康状况及相关影响因素,有针对性地对患者实施有效护理干预.方法 对60例宫颈癌放化疗患者应用抑郁自评量表(SDS)、焦虑自评量表(SAS)和自行设计的影响因素调查表进行调查分析,同期在潮汕4个地区抽取60名健康女性作为对照组进行调查对比;并结合影响因素对病例组实施护理干预7d后再次进行心理评估.结果 宫颈癌放化疗患者SDS、SAS得分分别为(56.1±7.7)、(45.2±7.5),显著高于健康女性调查得分(P＜0.001);进行护理干预7d后,宫颈癌放化疗患者SDS、SAS得分与干预前得分比较差异有统计学意义(P＜0.05).影响患者心理健康因素以担心住院费用、不了解与疾病有关的医学知识、对疾病感到恐惧、家庭社会影响、治疗副作用、担心预后最为突出.结论 宫颈癌放化疗患者这个特殊群体心理健康状况极差,在治疗疾病的同时,护理人员根据影响因素对患者进行心理疏导与支持,改善患者焦虑抑郁情绪,促进疾病康复,意义重大.     

Comparing EQ-5D-3L and EQ-5D-5L in measuring the HRQoL burden of 4 health conditions in China

The European Journal of Health Economics - EQ-5D-3L has been used in the National Health Services Survey of China since 2008 to monitor population health. The five-level version of EQ-5D was...     

腔隙性脑梗塞133例临床分析

本文对腔隙性脑梗塞（简称LI）133例进行了临床、CT及MRI分析，结果认为LI的病因是多方面的，有近半数的LI病例并无特异的阳性体征，过多分型无实际意义，MRI对LI的诊断优于CT，其中以T1T2加权都显示有病理意义，LI的典型临床表现需结合MRI的特点和CT来协助诊断。     

Interaction of six protoberberine alkaloids with human organic cation transporters 1, 2 and 3

1.?Organic cation transporters (OCTs) play an important role in drug safety and efficacy. Protoberberine alkaloids are ubiquitous organic cations or weak bases with remarkable biological actives. This study was to elucidate the potential interaction of alkaloids (coptisine, jatrorrhizine, epiberberine, berberrubine, palmatine and corydaline) with OCTs using Madin–Darby canine kidney (MDCK) cells stably expressing human OCT1, OCT2 and OCT3.

2.?All the tested alkaloids significantly inhibited the uptake of MPP⁺, a model OCT substrate, in MDCK-hOCTs cells with the IC₅₀ of 0.931–9.65?μM. Additionally, coptisine, jatrorrhizine and epiberberine were substrates of all the hOCTs with the K_m of 0.273–5.80?μM, whereas berberrubine was a substrate for hOCT1 and hOCT2, but not for hOCT3, the K_m values were 1.27 and 1.66?μM, respectively. The transport capacity of coptisine in MDCK cells expressing the variants of hOCT1-P341L or hOCT2-A270S was significantly higher than that in wild-type (WT) cells with the Cl_int (V_max/K_m) of 379?±?7.4 and 433?±?5.7?μl/mg protein/min, respectively.

3.?The above data indicate that the tested alkaloids are potent inhibitors, and coptisine, jatrorrhizine, epiberberine and berberrubine are substrates of hOCT1, hOCT2 and/or hOCT3 with high affinity. In addition, the variants (OCT1-P341L and OCT2-A270S) possess higher transport capacity to coptisine than WT hOCTs.