Active N-Ras and B-Raf inhibit anoikis by downregulating Bim expression in melanocytic cells

B-Raf and N-Ras proteins are often activated in melanoma, yet their roles in producing inherent survival signals are not fully understood. In this study, we investigated how N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis induced by detachment from the extracellular matrix (anoikis). We found that expression of constitutively active N-RAS(Q61K) and B-RAF(V600E) downregulated the proapoptotic Bim protein in an immortalized melanocyte cell line. Bim is one of the main proapoptotic mediators of anoikis. Western blot analysis showed that detachment increased Bim expression in melanocytes, and Annexin V staining indicated that detachment induced cell death significantly in melanocytes. Blocking Bim expression by using RNAi vectors or by expressing N-RAS(Q61K) significantly inhibited anoikis in melanocytes. In summary, this report indicates that N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis in part by downregulating Bim expression, suggesting that Bim is a possible treatment target for overriding melanoma's inherent defenses against cell death.     

HDV/HBV感染树鼩肝组织ICE表达及肝细胞凋亡

目的 探讨HDV/HBV感染树鼩肝组织中ICE表达与HDV感染之间的关系,以及ICE在丁型肝炎肝细胞凋亡中的作用。 方法 采用免疫组化技术对45份HDV感染树鼩肝组织中HDVAg,ICE的表达进行了检测;应用原位末端标记技术对肝组织凋亡进行检测;并应用免疫组化双重染色对HDVAg,ICE的表达以及肝细胞凋亡进行了检测。 结果 肝组织45份中有43份可检出ICE(阳性率96％),有41份可检出凋亡细胞(阳性率91％),ICE在肝细胞浆和(或)膜上表达,以肝细胞浆内表达为主,HDVAg表达与ICE表达之间有显著相关性X~2=36.2(P<0.05),HDVAg表达越强,ICE表达越强,凋亡阳性细胞在肝细胞索多呈散在分布,在坏死灶中也可检出,凋亡在HDVAg阳性和阴性细胞中均可发生,以在HDVAg阳性细胞内发生为主,ICE表达与肝细胞凋亡之间有显著相关性X~2=35.6(P<0.05),ICE表达越强,凋亡阳性细胞越多。 结论 丁型肝炎病毒感染和未感染的肝细胞均可发生凋亡,但凋亡只在少数细胞内发生;HDV可诱导ICE表达,ICE在肝细胞凋亡中起重要作用。     

Hyperthermia induces endoplasmic reticulum-mediated apoptosis in melanoma and non-melanoma skin cancer cells

Hyperthermia has been revived as a promising approach for cancer treatment. To understand the underlying mechanisms of hyperthermic killing of cancer cells, we examined the cytotoxic effects of hyperthermia on various skin cancer cell lines using cell viability, morphological analyses, and caspase activation assays. Hyperthermia induced cytotoxicity in a time- and temperature-dependent manner. At middle dose/time combinations, heat-induced apoptosis, whereas at higher doses, necrosis was the mechanism of cell death. To investigate the mechanisms of hyperthermia-induced apoptosis, we examined the activation of extrinsic (Caspase 8) and intrinsic (Caspase 9) apoptotic pathways. Hyperthermia did not activate Caspases 8 or 9, but did activate Caspase 3/7, suggesting a non-conventional apoptotic pathway. Last, analysis of Grp78 expression and Caspase 12 or 4 activation indicated that hyperthermia induced endoplasmic reticulum-mediated apoptosis. Thus, hyperthermia induced apoptosis in two types of skin cancer cells through endoplasmic reticulum-mediated apoptosis and not through the classical intrinsic or extrinsic apoptosis pathways. Hyperthermia may be a promising treatment for basal cell carcinoma and melanoma, bypassing the antiapoptotic defenses concentrated in the intrinsic and extrinsic apoptosis pathways. These results also raise the possibility that heat may be combined with other approaches for induction of apoptosis to achieve synergistic killing of skin cancers.     

"Making a connection": BSN students' perceptions of their reminiscence experiences with older adults

The projected increase in the diversity of the older adult population in the United States has generated a demand for nurses prepared to care for older adults from different cultural backgrounds. Nurse educators are challenged to develop innovative experiences to help prepare students who are competent in gerontological nursing and sensitive to cultural differences. The purpose of this study was to examine baccalaureate nursing students' perceptions of their reminiscence experiences with older adults. Forty-one nursing students who participated in a reminiscence education program during their clinical practicum completed an open-ended questionnaire. Data were analyzed, and three major themes emerged: "Making a Connection," "Seeing the World Through Their Eyes," and "Benefits of Reminiscence." Results indicate that implementing reminiscence education programs in clinical experiences can help students develop gerontological nursing skills, increase their cultural sensitivity, and improve their care of older adults.     

糖尿病大鼠卵巢组织中细胞色素C、线粒体Ca2+变化与灵芝孢子粉的干预

目的:以卵巢组织中细胞色素C、线粒体Ca2 和性激素水平为观察指标,观察灵芝孢子粉对2型糖尿病大鼠卵巢组织的保护作用。方法:实验于2006-06/08在佳木斯大学黑龙江省小儿神经康复重点实验室完成。①实验对象:Wistar雌性大鼠50只,随机分为对照组10只,2型糖尿病模型组20只,灵芝孢子粉组20只。②实验方法:大鼠禁食16～18h,自由饮水,模型组及灵芝孢子粉组大鼠经尾静脉一次性按25mg/kg注射2%链脲佐菌素,正常对照组尾静脉注射等量柠檬酸钠-柠檬酸缓冲液。正常饮食喂养2周后,进行糖耐量试验,模型组和灵芝组以糖耐量异常者保留,余去除,并改喂高脂高糖饮食,灵芝孢子粉组另加灵芝孢子粉[250mg/(kg·d)]持续10周,实验结束前一天再次做糖耐量试验。③实验评估:实验结束后,各组动物均禁食12h,乙醚吸入浅麻醉,内眦静脉取血待测血清胰岛素。解剖出卵巢,待测线粒体细胞色素C、线粒体Ca2 含量。结果:选用Wistar雌性大鼠50只,结果分析数量每组8只。①葡萄糖耐量试验:实验开始及实验12周时,模型组大鼠均表现出糖耐量异常的变化(P<0.05),1h血糖增高显著(P<0.05)达到高峰,2h血糖仍较高;对照组大鼠30min血糖达到峰值,2h血糖基本恢复正常。②血清胰岛素和卵巢性激素水平:模型组血清胰岛素明显升高(P<0.05)。而灵芝孢子粉组与对照组比较差异无显著性。模型组雌二醇含量明显降低(P<0.05),卵胞刺激素含量、睾酮含量明显升高(P<0.05),而灵芝孢子粉组与对照组比较差异无显著性。③胞浆细胞色素C、线粒体细胞色素C、线粒体钙变化:模型组卵巢组织胞浆细胞色素C含量明显升高(P<0.05),模型组卵巢组织线粒体细胞色素C含量明显降低(P<0.05),模型组卵巢组织线粒体钙含量明显降低(P<0.05);而灵芝孢子粉组与对照组比较差异均无显著性。结论:灵芝孢子粉可降低糖尿病大鼠血清胰岛素、卵巢组织卵胞刺激素、睾酮、胞浆细胞色素C含量,调节卵巢组织雌二醇、线粒体细胞色素C、钙含量,对糖尿病大鼠卵巢组织具有一定保护作用。     

"Nobody ever asked me before": understanding life experiences of African American elders.

With the unprecedented growth in the African American elderly population, there exists an urgent need to prepare nurses to deliver culturally competent care. The purpose of this study was to increase the knowledge available about the cultural heritage, worldviews, and life experiences of African American elders. Reminiscence interviews were conducted with African American elders living in a medium-sized northeast urban community. Data were analyzed using Spiegelberg's phenomenological Method. The following themes emerged: (a) nobody ever asked me before, (b) stories of discrimination, (c) coping with discrimination, (d) the hurt of discrimination, and (e) self-discoveries. Nurses, through the use of reminiscence, can gain insight into the cultural heritage, worldviews, and life experiences of African American elders and improve their ability to deliver culturally competent care to this population.