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摘要：目的探讨SDF-1／CXCR7对胃癌SGC-7901细胞合成及分泌炎症因子的影响及其机制。方法采用CXCR7的shRNA慢病毒表达载体感染人胃癌SGC-7901细胞，Real-timePCR及Westernblot检测CXCR7mRNA和蛋白表达；应用SDF-1干预，分为4组：阴性对照组（LushRNA-NC），LV-shRNA-NC＋SDF-1组，CXCR7沉默组（LV-shRNA-CXCR7），LV—shRNA-CXCR7＋SDF-1组。采用Real-timePCR检测炎症因子TNF-a、IL-113、IL-6、IL-8的mRNA表达；采用ELISA检测细胞上清液TNF-a、IL-113、IL-6、IL-8的蛋白含量；采用Westernblot检测NF-kB通路的变化。结果①Real-timePCR及Westernblot结果提示，CXCR7沉默组sac-7901细胞CXCR7mRNA及蛋白的表达水平较阴性对照组显著降低（P均〈0．01），阴性对照组与空白对照组间无明显差异。②与LV-shRNA．Nc组相比，Lv-shRNA-NC＋SDF-1组IL-6及IL-8的mRNA表达及分泌明显增加（P〈0．01），LV-shRNA-CXCR7组IL-6及IL8mRNA表达及分泌减少（P〈0．05）；与LV—shRNA—NC＋SDF-1组相比，Lv-shRNA-CXCR7＋SDF-1组IL-6及IL-8mRNA表达及分泌明显减少（P〈0．01）。而TNF-Ⅸ及IL-18的mRNA表达及分泌在4组间无明显差异。③NF-eBp65核内表达、t-IkBa及p-IKBa表达在4组间均无明显差异。站论SDF-1可能通过CXCR7促进SGC-790l细胞合成及分泌炎症因子IL-6及IL-8，但不依赖于NF-KB通路。

目的探讨正常骨髓基质细胞对残留耐药Jurkat细胞凋亡的促进作用及其可能机制。方法体外分离培养急性淋巴细胞白血病患者和健康供者骨髓基质细胞（BMSCs）,分别模拟白血病和正常骨髓造血微环境,并与获得柔红霉素（DNR）耐药的Jurkat细胞（Jurkat/DNR细胞）共培养。绘制悬浮培养和与BMSCs共培养4d的Jurkat/DNR细胞的增殖曲线,并检测悬浮培养及共培养14、1、0d的Jurkat/DNR细胞的caspase3/7活性和bcl-2、bax、DAPK1 mRNA表达情况。结果与骨髓基质细胞共培养比较,悬浮培养的Jurkat/DNR细胞生长受到明显抑制。共培养41、0d后,Jurkat/DNR细胞caspase3/7活性升高,且共培养10d的活性高于共培养4d（P〈0.05）。共培养4、10d后,Jurkat/DNR细胞bcl-2表达增加,共培养14、1、0d后,死亡相关蛋白激酶1（DAPK1）表达增加（P〈0.05）。而bax表达在各时间点间差异无统计学意义（P〉0.05）。结论正常骨髓基质细胞能促进Jurkat/DNR凋亡,其机制可能与过表达的DAPK1诱导Jurkat/DNR细胞凋亡和bcl-2转录下调c、aspase3/7活性升高有关。

目的研究低强度氦氖（He-Ne）激光照射对小鼠骨髓基质细胞（BMSCs）表面细胞间黏附分子-1（ICAM-1）、血管细胞间黏附分-子1（VCAM-1）表达的影响。方法 30只小鼠随机分为3组：对照组（A组）,2.75J/cm2激光组（B组）,4.20J/cm2激光组（C组）,每组10只。激光组建立低强度He-Ne激光体外照射小鼠模型,对照组不作任何处理。分离小鼠BMSCs,并进行原代、传代培养。采用倒置相差显微镜、光镜及透射电镜对BMSCs形态进行观察;采用流式细胞术检测低强度He-Ne激光照射对小鼠BMSCs表面VCAM-1和ICAM-1蛋白表达的影响。结果倒置显微镜和光镜观察到BMSCs呈贴壁生长,细胞呈梭形或不规则,有突起;电镜观察到细胞内粗面内质网、分泌小泡、线粒体等细胞器丰富。激光组BMSCs增殖加快,达到80%细胞融合时间短。2.75J/cm2激光组和4.20J/cm2激光组均能增加小鼠BMSCs表面VCAM-1和ICAM-1蛋白的表达。其中,4.20J/cm2激光组较2.75J/cm2激光组作用更明显（P〈0.01）。结论低强度He-Ne激光能促进小鼠BMSCs表面VCAM-1和ICAM-1蛋白的表达。

目的探讨趋化因子SDF-1及其受体CXCR4在上皮性卵巢肿瘤组织中的表达及临床意义。方法应用免疫组织化学SP法检测10例正常卵巢上皮组织、21例卵巢良性肿瘤、19例交界性卵巢肿瘤、30例卵巢癌原发灶和11例相应盆腔腹膜转移灶组织中SDF-1和CXCR4蛋白表达情况。结果正常卵巢上皮组织SDF-1和CXCR4表达阴性，卵巢良性肿瘤低表达SDF-1（9．52％），CXCR4表达阴性，与正常卵巢及良性卵巢肿瘤相比，交界性卵巢肿瘤、卵巢癌原发灶及转移灶表达较高水平的SDF-1与CXCR4（63．16％、93．33％、90．91％；47．37％、63．33％、63．64％）。交界性卵巢肿瘤中SDF-1和CXCR4表达无显著相关性（P=0．460）；而卵巢癌原发灶中SDF-1和CXCR4表达呈正相关（P〈0．05）；SDF-1的表达与卵巢癌患者的临床分期、组织学分级无显著相关性（P〉0．05），而与患者有无腹水有一定相关性（P〈0．05），CXCR4的表达与卵巢癌患者的临床分期、组织学分级及患者有无腹水无显著相关性（P〉0．05）。结论SDF-1／CXCR4的表达与细胞的恶性转化有关，可能参与了卵巢恶性肿瘤的发生、发展、侵袭与转移。

Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.

The importance of the vascular supply for bone is well-known to orthopaedists but is still rather overlooked within the wider field of skeletal research. Blood supplies oxygen, nutrients and regulatory factors to tissues, as well as removing metabolic waste products such as carbon dioxide and acid. Bone receives up to about 10% of cardiac output, and this blood supply permits a much higher degree of cellularity, remodelling and repair than is possible in cartilage, which is avascular. The blood supply to bone is delivered to the endosteal cavity by nutrient arteries, then flows through marrow sinusoids before exiting via numerous small vessels that ramify through the cortex. The marrow cavity affords a range of vascular niches that are thought to regulate the growth and differentiation of hematopoietic and stromal cells, in part via gradients of oxygen tension. The quality of vascular supply to bone tends to decline with age and may be compromised in common pathological settings, including diabetes, anaemias, chronic airway diseases and immobility, as well as by tumours. Reductions in vascular supply are associated with bone loss. This may be due in part to the direct effects of hypoxia, which blocks osteoblast function and bone formation but causes reciprocal increases in osteoclastogenesis and bone resorption. Common regulatory factors such as parathyroid hormone or nitrates, both of which are potent vasodilators, might exert their osteogenic effects on bone via the vasculature. These observations suggest that the bone vasculature will be a fruitful area for future research.

Acute myeloid leukemia （AML） is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow （BM） niche is critical to the maintenance and retention of hematopoietic stem cells （HSC）, including leukemia stem cells （LSC）, and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

Mesenchymal stromal cells（MSCs） are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like ＂wounds that do not heal.＂ In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.

Sites of implantation with compromised biology may be unable to achieve the required level of angiogenic and osteogenic regeneration. The specific function and contribution of different cell types to the formation of prevascularized, osteogenic networks in co-culture remains unclear. To determine how bone marrow-derived mesenchymal stromal cells （BMSCs） and endothelial cells （ECs） contribute to cellular proangiogenic differentiation, we analysed the differentiation of BMSCs and ECs in standardized monolayer, Transwell and co-cultures. BMSCs were derived from the iliac bone marrow of five patients, characterized and differentiated in standardized monolayers, permeable Transwells and co-cultures with human umbilical vein ECs （HUVECs）. The expression levels of CD31, von Willebrand factor, osteonectin （ON） and Runx2 were assessed by quantitative reverse transcriptase polymerase chain reaction. The protein expression of alkaline phosphatase, ON and CD31 was demonstrated via histochemical and immunofluorescence analysis. The results showed that BMSCs and HUVECs were able to retain their lineage-specific osteogenic and angiogenic differentiation in direct and indirect co-cultures. In addition, BMSCs demonstrated a supportive expression of angiogenic function in co-culture, while HUVEC was able to improve the expression of osteogenic marker molecules in BMSCs.

Osteoporosis is a serious public bone metabolic disease. However, the mechanisms underlying bone loss combined with ageing, which is known as senile osteoporosis, remains unknown. Here we show the detailed phenotype of this disease caused by SIRT6 knock out （KO） in mice. To the best of our knowledge, this is the first study to reveal that SIRT6 is expressed in both bone marrow stroma cells and bone-related cells in both mouse and human models, which suggests that SIRT6 is an important regulator in bone metabolism. SIRT6-KO mice exhibit a significant decrease in body weight and remarkable dwarfism. The skeleton of the SIRT6-KO mouse is deficient in cartilage and mineralized bone tissue. Moreover, the osteocalcin concentration in blood is lower, which suggests that bone mass is markedly lost. Besides, the tartrate-resistant acid phosphatase 5b （TRAP5b） concentration is much higher, which suggests that bone resorption is overactive. Both trabecular and cortical bones exhibit severe osteopenia, and the bone mineral density is decreased. Moreover, double-labelling analysis shows that bone formation is much slower. To determine whether SIRT6 directly regulates bone metabolism, we cultured primary bone marrow stromal cells for osteogenesis and osteoclastogenesis separately to avoid indirect interference in vivo responses such as inflammation. Taken together, these results show that SIRT6 can directly regulate osteoblast proliferation and differentiation, resulting in attenuation in mineralization. Furthermore, SIRT6 can directly regulate osteoclast differentiation and results in a higher number of small osteoclasts, which may be related to overactive bone resorption.