PI-3K/Akt/GSK-3p signaling cascades stimulated by insulin like growth factor-Ⅰcontribute to multiple myeloma cells proliferation and survival

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Significant progress in molecular mechanisms of signaling pathways underlying the survival and/or proliferation of these cells has been achieved. Interleukin 6 (IL-6) is an important cytokine leading to multiple myeloma (MM) cells growth and survival. However, some MM cells isolated from MM patients are poorly responsive to IL-6 stimulation or IL-6 independent. This phenomenon raises the possibility that other growth factors may also be involved in the development of MM. Insulin like growth factor-Ⅰ(IGF-Ⅰ) plays an important role in the     

Role of Baicalein in the regulation of proliferation and apoptosis in human myeloma RPMI8226 cells

Multiple myeloma （MM） is a uniformly fatal disease characterized by a clonal proliferation of neoplastic plasma cells in the bone marrow and is the second most commol hematological malignancy.1 At present, a cure for multiple myeloma has not been achieved with chemotherapeutic regimen, and many patients die of drug-resistant disease. Thus, the development of new effective anticancer agents to treat both early and advanced MM seems to be an attractive perspective.     

Relation Between Cellular Senescence and Liver Diseases

Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline.Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.     

Matrine and CYC116 Synergistically Inhibit Growth and Induce Apoptosis in Multiple Myeloma Cells

Objective:To investigate whether CYC116 can potentiate matdne-dependent growth inhibition and apoptosis in multiple myeloma(MM)cells.Methods:The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established.Myeloma RPMI8226cells were treated with matrine alone or combined with CYC116 for 24 h.Cell proliferation was measured using an MTT-T assay and apoptosis induction was evaluated by flow cytometry.Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.Results:Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells.Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments.Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9,caspase-3,and poly adenosine diphosphate ribose polymerase(PARP)and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factorκB(NF-κB).Conclusions:CYC116 enhances the growth inhibitory and apoptotic effects of matdne on MM cells.     

Human cytomegalovirus protects multiple myeloma cell line KM3 cells from apoptosis induced by growth factor withdrawal

Background There is a higher rate of cytomegalovirus (CMV) reactivation in patients with multiple myeloma after an autologous stem cell transplantation, but no attention has been given thus far to a possible pathogenetic interplay between CMV and multiple myeloma. CMV can infect many kinds of cells, and CMV infection has been shown to inhibit apoptotic responses in several cell systems. In this study the authors investigated the alterations in apoptosis in the multiple myeloma cell line KM3 after infection with CMV and DroDosed a Possible mechanism.Methods KM3 cells were infected with 100, 10, or 1 TCID50 of CMV and then cultured in serum-free RPMI 1640. An RT-PCR-based assay was used to detect mRNA expression of CMV-IE,glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and IL-6 in CMV-infected and mock-infected cells. Flow cytometry was used to detect apoptotic cells. CMV particles and apoptotic cells were also examined with an electron microscope.Results CMV-infected KM3 cells clearly expressed immediate early (IE) antigen mRNA when compared to uninfected cells, and there were fewer apoptotic cells among cells treated with 100 or 10 TCID50 of CMV after culturing in serum-free RPMI 1640. CMV particles were observable in infected cells under an electron microscope. Expression of IL-6 mRNA increased after infection.Conclusion CMV can infect the multiple myeloma cell line KM3, inhibit the apoptotic response in these cells after apoptosis induction in serum-free culture, and increase the expression of IL-6 mRNA.     

Effects of arsenic trioxide on voltage-dependent potassium channels and on cell proliferation of human multiple myeloma cells

Arsenic trioxide （ATO） can induce cellular apoptosis ,and inhibit the activities of multiple myeloma （MM）cells in vitro, but how it works is not very clear. Recent studies showed that ATO worked on the voltagedependent potassium channel and L-type calcium channel in myocardial cells, but the effect of ATO on ion channels of tumor cells was rarely reported. As the potassium channel plays an important role in controlling cell proliferation, we studied the effects of ATO on the voltage-dependent potassium current （Ikv） of the voltage-dependent potassium channel in an MM cell line, and probed into the relationship between changes of the Ikv caused by ATO and cell proliferation.     

Role of silencing phosphatase of regenerationg liver-3 expression by microRNA interference in the growth of gastric cancer

Background Accumulated evidences demonstrate that phosphatase of regeneration liver-3 （PRL-3） is associated with metastasis of multiple tumor types, and has been validated as a potential therapeutic target for metastasis. High expression of PRL-3 was implicated in lymph node metastasis of gastric cancer. In the present study, we investigated the role of silencing PRL-3 expression by microRNA （miRNA） interference in gastric cancer growth. Methods RNA interference, mediated by recombinant lentivirus expressing artificial PRL-3 miRNA, was employed to knockdown PRL-3 expression in human SGC7901 gastric cancer cells. MTT assay and tumor implantation experiment were conducted to determine the role of PRL-3 in the proliferation of SGC7901 cells and tumor growth. Results Transfection of recombinant lentivirus expressing artificial PRL-3 miRNA significantly suppressed the proliferation of SGC7901 cells in vitro. The implanted tumor size of the PRL-3 transfection group was （1.92±0.18） cm^3, significantly smaller compared with controls （P 〈0.001）. Conclusions Knockdown of PRL-3 significantly suppressed the proliferation of SGC7901 cells in vitro and tumor growth in vivo. PRL-3 plays a key role in the growth of gastric cancer. PRL-3 should be considered as a potential therapeutic target.     

Yb3+/Er3+/Tm3+三掺YF3上转换发光性质的研究

以氟化钇（YF₃）为基质材料,采用共沉淀法合成了YF₃：Yb³⁺/Er³⁺/Tm³⁺上转换发光材料。采用X射线衍射仪（XRD）、热重差热分析仪（DTA）和荧光光谱分析对材料的物相结构、烧结温度和发光性质进行了研究。结果表明,掺入稀土离子没有改变YF₃晶体结构,在980 nm近红外波长激发下,出现了多个波段的发光现象,Yb³⁺、Er³⁺、Tm³⁺不同的掺杂量分别对应于材料不同的发光规律。本文还探讨了上转换发光机制,确定了该体系荧光粉的最佳烧结温度。     

SiO2-Bi2O3-BaF2-AlPO4玻璃掺杂Ho3+/Tm3+/Yb3+的发光性能

以铋硅酸盐玻璃（SiO₂-Bi₂O₃-BaF₂-AlPO₄）为基质,通过掺杂Ho³⁺、Tm³⁺、Yb³⁺稀土离子,制备激光波长为2 μm的光纤激光器。对玻璃的声子能量、物理和光学性能进行了研究,确定基质配方为50SiO₂-40Bi₂O₃-5BaF₂-5AlPO₄（SBBA,其中化学式前的系数为对应物质的摩尔分数,下同）。在玻璃基质中分别掺杂0.5Ho₂O₃-2.0Yb₂O₃（HY）、0.5Ho₂O₃-0.5Tm₂O₃-2.0Yb₂O₃（0.5HTY）及0.75Ho₂O₃-0.75Tm₂O₃-3.0Yb₂O₃（0.75HTY）,研究了980 nm激发波长下样品的吸收、发射光谱和Judd-Oflet理论光谱参数。研究发现SBBA-0.75HTY中Ho³⁺的吸收截面、发射截面（σ_em）、FWHM（半峰宽）×σ_em数值最大,分别为7.38×10^-21、10.54×10^-21 cm²和19.71×10^-26 cm³。掺入Tm₂O₃改善了玻璃激光器性能,且当Yb³⁺/Tm³⁺/Ho³⁺物质的量之比一定时,增加稀土离子含量,可加强红外发光及增益效果。     

SRSV/3T3和NIH/3T3细胞膜的分离和蛋白质组分的初步比较

应用甘油低渗两相分配法分离了SRSV/3T3细胞质膜(SM)和NIH/3T3细胞质膜(NM)。经Na~+、K~+-ATP酶和葡萄糖-6-磷酸酶等标志酶活性鉴定,表明SM和NM纯度较高。经SDS-PAGE分析比较,发现SM和NM的蛋白质组分有较明显差异。SM有7种独特的组分,分子量分别为2.29×10~(-22)、2.18×10~(-22)、9.79×10~(-23)、9.60×10~(-23)、8.63×10~(-23)、5.49×10~(-23)和4.78×10~(-23)kg。NM有两种特有的组分(1.15×10~(-22)和4.17×10~(-23)kg)。在彼此共有的蛋白质组分中,也有许多组分在含量和电泳迁移速度上存在着程度不同的区别。     

ErbB3/HER3和erbB4/HER4在肺癌中的表达

目的：探讨HER3和HER4(Human epidermal-growth-factor receptor 3 amd 4)过度表达与肺癌临床病理的关系，明确erbB3和erbB4癌基因在肺癌生长中的作用。方法：用免疫组化法分别检测20例非癌肺石蜡组织及70例肺癌（43例鳞癌和27例腺癌）石蜡组织中HER3和HER4的表达，并采用肺癌组织染色减去癌旁上皮组织染色≥2 的标准，对它们在肺癌中是否呈过度表达进行判断。结果：HER3和HER4在支气管粘膜细胞及肺泡细胞存在阳性表达（ ）；HER4在正常支气管细胞和肺泡细胞表达率的差异有统计学意义；肺癌中存在HER4的过度表达，但无HER3的过度表达；肺癌中HER4的过度表达与肺癌病理类型、分化程度无相关性，而与肺癌淋巴结转移、TNM分期、患者术后生存率相关。结论：erbB4是晚期肺癌生长的调控基因之一，人为地干预HER4的过度表达可能是一种治疗晚期肺癌的有效方法。ErbB3基因在肺癌细胞增殖中可能作用有限。     

PHBV在玻璃化转变温度以上的物理老化行为

研究了聚（3-羟基丁酸酯-3-羟基戊酸酯） （简称PHBV）和含成核剂氮化硼（BN）的PHBV在30 ℃等温条件下老化过程中的热性能和弹性性能随老化时间的变化规律。根据聚合物三相模型理论,通过调制式差示扫描量热法（MDSC）计算得到PHBV的可动无定形相含量（X_MA）、刚直无定形相含量（X_RA）和结晶相含量（X_c）。结果表明,成核剂的加入对抑制PHBV的老化有明显效果。通过热性能、弹性性能和晶体形貌分析进一步证实了这一结果。     

gpc3/mxr7基因的原核表达及其多克隆抗体的制备

目的：通过原核表达并纯化GPC3蛋白，免疫家兔获得抗—GPC3多克隆抗体，为深入研究gpc3／mxr7基因的功能及其临床应用奠定基础。方法：将gpc3／mxr7基因片段亚克隆至pPROEX^TM HTb原核表达载体，采用融合6—his的融合蛋白方法原核表达GPC3蛋白质，纯化蛋白后免疫家兔，鉴定并纯化出抗—GPC3多克隆抗体。结果；原核诱导表达出GPC3蛋白，免疫家兔后获得多克隆抗体，经鉴定为抗--GPC3特异性多克隆抗体，并能识别原核、真核表达的外源性及HepG2和Hu-h7细胞内源性GPC3蛋白。结论：GPC3蛋白多克隆抗体能特异识别GPC3蛋白，可应用于gpc3／mxr7基因的功能研究，并为临床原发性肝癌的血清学早期诊断提供新的标记物。     

O3/UV和O3/H2O2氧化法处理聚丙烯酰胺采油废水

为降低油田采油废水的化学需氧量（COD）负荷,提高其可生化性,采用O₃/UV和O₃/H₂O₂氧化法对聚丙烯酰胺采油废水进行处理,分别考察了氧化时间、H₂O₂与O₃物质的量之比、pH以及紫外灯功率对采油废水处理效果的影响。结果表明,与采用单独臭氧氧化相比,O₃/UV以及O₃/H₂O₂联用技术对采油废水中的COD及聚丙烯酰胺（PAM）的去除效果更为显著,废水可生化性均有所提高,且O₃/H₂O₂氧化法对采油废水的可生化性提高程度更大。O₃/UV氧化法对于聚丙烯酰胺采油废水可生化性影响的最佳条件为：pH=8.0,O₃质量浓度为19.7 mg/L,紫外灯功率为18 W,氧化时间为30 min,可生化性（B/C）提高至0.092;O₃/H₂O₂氧化法对于聚丙烯酰胺采油废水可生化性影响的最佳条件为：pH=8.0,O₃质量浓度为19.7 mg/L,H₂O₂与O₃物质的量之比为0.3,氧化时间为30 min,B/C提高至0.175。氧化预处理提高了废水的可生化性,减轻了后续生化处理压力。     

体外观察维甲酸对NIH/3T3细胞的抑制作用

目的评价维甲酸(RA)对NIH/3T     

新风胶囊通过miR-23a-3p/PTEN/PI3K/AKT/mTOR抑制骨关节炎CD4+T与软骨细胞共培养的免疫炎症

目的 观察新风胶囊（XFC）含药血清通过调控miR-23a-3p /PTEN/PI3K/AKT/mTOR信号通路抑制骨关节炎（OA）CD4+T与软骨细胞共培养中免疫炎症反应的作用机制。方法 选取30例OA患者（OA组）及30例正常人（NC组）检测miR-23a-3p、10号染色体同源丢失性磷酸酶-张力蛋白基因（PTEN）、磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶B（AKT）、哺乳动物雷帕霉素靶蛋白（mTOR）的表达,观察临床指标：红细胞沉降率（ESR）、超敏C反应蛋白（hs-CRP）、IgA、IgG、IgM、补体 C3、补体C4的表达,并观察通路与临床指标的相关性。观察 30 例 OA 患者经 XFC 治疗后通路及临床指标的变化。分离及提取 OA-CD4 +T 细胞,transwell小室培养OA-CD4+T细胞与OA-CH,SD大鼠给药灌胃制备XFC含药血清;采用CCK8法检测OA-软骨细胞的细胞增殖;双荧光素酶报告实验分析miR-23a-3p和PTEN的靶向关系;RT-PCR技术检测共培养细胞中miR-23a-3p、PTENmRNA、PI3KmRNA、AKTmRNA、mTORmRNA 的表达;采用 ELISA 法检测 IL-1β、IL-6、IL-10、TNF-α的水平;Western blotting 检测PTEN、PI3K、AKT、p-AKT、mTOR、p-mTOR蛋白表达。结果 与NC组相比,OA组miR-23a-3p、PTEN、PI3K、AKT、IL-1β、IL-6、TNF-α表达显著上调,而PTEN、IL-10表达显著下调（P<0.01）;相关性分析表明：miR-23a-3p与IL-6呈正相关（P<0.01）,PI3K与IL-10呈正相关,mTOR与IL-6、IL-10、补体C3、补体C4呈正相关（P<0.01或P<0.05）;加入XFC含药血清,miR-23a-3p及PI3K/AKT/mTOR通路被抑制,L-1β、IL-6、TNF-α表达水平下降、IL-10表达水平升高（P<0.01）;Model组miR-23a-3p、PI3K、AKT、mTOR、IL-1β、IL-6和TNF-α表达水平升高,PTEN、IL-10表达水平降低（P<0.01）;miR-23a-3p经过表达后,miR-23a-3p、PI3K、AKT、mTOR、IL-1β、IL-6和TNF-α表达水平显著升高,PTEN、IL-10表达水平显著降低（P<0.01或P<0.05）;XFC组IL-1β、IL-6、TNF-α表达降低,IL-10表达升高,miR-23a-3p、PI3K、AKT、mTOR表达下调,PTEN表达上调（P<0.01或P<0.05）。结论 XFC可通过下调miR-23a-3p的表达,抑制PTEN/PI3K/AKT/mTOR通路的活化,改善IL-1β、IL-6,IL-10和TNF-α的表达,降低OA患者炎症反应。