Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARα protein degradation

Arsenic trioxide (As₂O₃) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As₂O₃-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As₂O₃, which results in initiation of PML-RARa degradation. However, after injection, As₂O₃ is rapidly methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid (MMA^III) and dimethylarsinous acid (DMA^III), therefore, it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against APL. Here we have shown the role of As₂O₃ (as iAs^III) and its intermediate metabolites (i.e., MMA^III/DMA^III) in NB4 cells. Inorganic iAs^III predominantly showed induction of cell differentiation, while MMA^III and DMA^III specifically showed to induce mitochondria and endoplasmic reticulum-mediated apoptosis, respectively. On the other hand, in contrast to iAs^III, MMA^III showed stronger binding affinity for ring domain of PML recombinant protein, however, could not induce PML protein SUMOylation and ubiquitin/proteasome degradation. In summary, our results suggest that the binding of arsenicals to the ring domain of PML proteins is not associated with the degradation of PML-RARa fusion protein. Moreover, methylated arsenicals can efficiently lead to cellular apoptosis, however, they are incapable of inducing NB4 cell differentiation.     

Elevated expression of HABP1 is correlated with metastasis and poor survival in breast cancer patients

Hyaluronan-binding protein 1 (HABP1) is a protein with high affinity for HA, and has been reported to be upregulated in cancer cells. In this study, we show that silencing HABP1 inhibits proliferation, and suppresses the migration and invasion ability of breast cancer cell lines. In addition, silencing HABP1 remarkably slows down tumor growth in mice. We examined the correlation between HABP1 expression and clinicopathological parameters using immunohistochemistry in patients with breast cancer. The results indicate that HABP1 is overexpressed in cancer tissue, and its high levels are related to lymph node metastasis (P = 0.032) and tumor stage (P = 0.041). Moreover, high HABP1 expression is correlated with poor overall survival in breast cancer patients (P = 0.018), and is a signifi cant independent prognostic indicator. Our fi ndings suggest that HABP1 regulates proliferation and migration of breast cancer cells. HABP1 may be a useful independent predictor of outcomes in patients with breast cancer.     

雌激素受体基因多态性与儿童孤独症临床表型特征的关联研究

【目的】 探讨雌激素受体(estrogen receptor,ER)基因多态性与儿童孤独症临床表型特征的关系。 【方法】 应用TaqMan荧光探针Real-Time PCR的分析方法对127名孤独症患儿进行ERα的单核苷酸多态性片断rs11155819和ERβ的单核苷酸多态性片断rs1152582的基因型测定。用儿童孤独症评定量表(Children Autism Rating Scale,CARS)评价孤独症患儿临床表型特征。 【结果】 孤独症病情严重程度在rs11155819和rs1152582的不同基因型之间的差异无统计学意义(P>0.05)。rs11155819基因型为C/T、T/T的孤独症儿童在语言交流项得分的差异有统计学意义(P=0.048)。rs1152582基因型为C/C、G/G的孤独症儿童在非言语交流项、活动水平项得分的差异有统计学意义(P=0.035;P=0.030)。 【结论】 rs11155819基因型中,携带T/T的患儿比携带C/T的患儿有更明显的语言交流障碍。rs1152582基因型中,携带C/C的患儿比携带G/G的患儿有更明显的非言语交流障碍和活动异常。     

行为问题儿童注意力及短时记忆力认知综合训练干预效果评价

目的探讨行为问题儿童的注意力与短时记忆能力的特点,进行认知综合训练干预,并对干预效果进行对比分析,探讨有效康复训练方案。方法收集在哈尔滨医科大学发育行为研究中心咨询和参训的6～14岁行为问题的儿童30例(包括26例注意力缺陷多动障碍儿童和4例高功能孤独症儿童)进行3.3.3系列智能学具和由国家医疗保健器具工程技术研究中心研发的智力流认知能力训练。选择年龄、性别、智商相匹配的正常儿童30名做为对照组。通过比较观察组自身前后结果以及观察组与对照组的结果比较分析干预效果。结果训练前行为问题儿童的注意力、记忆力、眼球运动水平明显低于正常儿童。经过认知综合训练后,观察组患儿的认知能力有明显提高,且效果显著。训练后的患儿注意力、记忆力及眼球追踪水平接近正常对照组儿童,且在比较分析中显示无统计学差异,干预效果明显。结论以3.3.3系列智能学具和智力流训练为主的综合认知训练对于改善行为问题儿童的注意力、短时记忆力及眼球追踪能力有显著的效果,可用于大范围开展此类患儿的康复治疗和训练。     

饮食诱导肥胖与肥胖抵抗大鼠糖类吸收比较

目的 探讨饮食诱导肥胖(DIO)大鼠与饮食诱导肥胖抵抗(DR)大鼠小肠糖类吸收功能的差异.方法 高脂饲料建立饮食诱导肥胖与肥胖抵抗大鼠模型,8周后比较2组大鼠体重、摄食量和食物效能;随机选取8只大鼠分别进行口服葡萄糖耐量试验和口服D-木糖耐量试验,比较各时间点血糖浓度和血清D-木糖浓度.结果 DIO大鼠摄食量(417.8 ±33.5) kJ/d和食物效能(1.5±0.1)×100 g/kJ均高于DR大鼠(379.3±40.2)kJ/d、(1.3±0.1)×100 g/kJ,差异均有统计学意义(均P＜0.05);口服葡萄糖耐量试验中DIO组曲线下面积[(16.5±1.2) mmol/(L·h)]＞DR组[(14.6±1.5) mmol/(L·h)],差异有统计学意义(t=-2.75,P＜0.05),口服D-木糖耐量试验2组大鼠曲线下面积差异无统计学意义.结论 高脂饮食诱导的肥胖与肥胖抵抗大鼠对葡萄糖的吸收存在差异,这可能在肥胖形成中起到一定作用.     

农药作业工人血清胆碱酯酶和对氧磷酶活力的影响因素及相关性研究

目的探讨有机磷类和氨基甲酸酯类农药作业工人血清胆碱酯酶(ChE)活力和对氧磷酶(PON)活力的影响因素及相关性。方法以81名生产有机磷类和氨基甲酸酯类农药作业工人为暴露组,同时,选择94名非农药企业工人作为对照组,通过问卷调查收集相关信息,测定血清生化指标[丙氨酸氨基转移酶(ALT)、谷氨酸氨基转移酶(AST)、γ-转肽酶(γ-GGT)、乳酸脱氢酶(LDH)活力及总蛋白(TP)、白蛋白(ALB)、总胆红素(TBIL)、尿素氮(BUN)、肌酐(Crea)、胆固醇(T-CH)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)含量]以及ChE和PON活力。结果两组人群在年龄、性别、吸烟率和饮酒率以及各项血清生化指标间均无显著性差异;仅暴露组人群工龄低于对照组,差异有统计学意义(P<0.05)。农药暴露人群血清ChE和PON活力均低于对照组(P<0.05),女性血清ChE活力显著低于男性(P<0.05);年龄较高(>32岁)人群血清的PON活力水平低于年龄较低人群(≤32岁),工龄较长(>4.5年)人群血清ChE活力和PON活力明显低于工龄较短(≤4.5年)工人。对照组人群血清ChE活力与PON活力呈正相关(P<0.05),而暴露组人群血清ChE活力与PON活力间无明显的相关关系。结论人群血清PON和ChE活力可以作为有机磷类农药暴露早期敏感性生物标志物,但尚不能确定ChE活力与PON活力之间有相关关系。     

OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism

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Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo （a） pyrene and chemopreventive mechanisms

AIM: To explore the inhibition of conjugated linoleic acidisomers in different purity (75 % purity c9,t11-, 98 % purityc9,t11- and 98 % purity t10,c12-CLA) on the formation offorestomach neoplasm and cheopreventive mechanisms.METHODS: Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The numbers of tumorand diameter of each tumor in forestomach were counted;the mice plasma malondialdehyde (MDA) were measuredby TBARS assay; TUNEL assay was used to analyze theapoptosis in forestomach neoplasia and the expression ofMEK-1, ERK-1, MKP-1 protein in forestomach neoplasm werestudied by Western Blotting assay.RESULTS: The incidence of neoplasm in B(a)P group, 75 %purity c9, t11-CLA group, 98 % purity cg,t11-CLA groupand 98 % purity t10, c12-CLA group was 100 %, 75.0 %(P＞0.05), 69.2 % (P＜0.05) and 53.8 % (P＜0.05) respectivelyand the effect of two CLA isomers in 98 % purity onforestomach neoplasia was significant; CLA showed noinfluence on the average tumor numbers in tumor-bearingmouse, but significantly decreased the tumor size, the tumoraverage diameter of mice in 75 % purity c9,t11-CLA group,98 % purity cg,t11-CLA group and 98 % purity t10, c12-CLAgroup was 0.157±0.047 cm, 0.127±0.038 cm and 0.128±0.077 cm (P＜0.05) and 0.216±0.088 cm in B(a)P group;CLA could also significantly increase the apoptosis cellnumbers by 144.00±20.31, 153.75±23.25, 157.25±15.95(P＜0.05) in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10,c12-CLA group (30.88±3.72 in BP group); but there were no significant differencesbetween the effects of 75 % purity c9,t11-CLA and twoisomers in 98 % purity on tumor size and apoptotic cellnumbers; the plasma levels of MDA in were increased by75 % purity c9,t11-ClA, 98 % purity c9,t11-CLA and 98 %purity t10,c12-CLA. The 75 % purity c9,t11-CLA showedstronger inhibition; CLA could also inhibit the expression ofERK-1 protein and promote the expression of MKP-1 protein,however no influence of CLA on MEK-1 protein was observed.CONCLUSION: Two isomers in 98 % purity show strongerinhibition on carcinogenesis. However, the inhibitorymechanisms of CLA on carcinogenesis is complicated, whichmay be due to the increased mice plasmaMDA, the inducingapoptosis in tumor tissues. And the effect of CLA on theexpression of ERK-1 and MKP-1 may be one of themechanisms of the inhibition of CLA on the tumor.     

“营养与食品卫生学”国家级精品资源共享课建设体会

文章总结了我院进行“营养与食品卫生学”国家级精品资源共享课建设的经验和体会,就课程建设原则和要求、课程设置、教学资源准备以及课程建设管理等方面进行了探讨,旨在为其他建设单位提供借鉴.     

巯基棉富集—火焰原子吸收法测定饮用水中镉铜铅的研究

采用巯基棉富集—火焰原子吸收法测定饮用水中镉、铜和铅，就其富集酸度、洗脱液及其温度进行了探讨。此法简单，快速，线性范围镉和铜是０．００４～０．０４μｇ／ｍｌ，铅是０．１～１．０μｇ／ｍｌ；相关系数镉０．９９９１，铜０．９９９６，铅０．９９９９；回收率镉９６．９％～１０５．０％，铜９８．１％～１０１．３％，铅１００．０％～１０１．０％；变异系数镉３．５％，铜１．７６％，铅５．２５％。