Chaetocin:a review of its anticancer potential and mechanisms

Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines.Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo.Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression,inducing cancer cell apoptosis(intrinsic and extrinsic),enhancing autophagy,inducing cell cycle arrest,as well as inhibiting tumour angiogenesis,invasion and migration.The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper,and the prospective applications of chaetocin in cancer prevention and therapy are also discussed.Our review provides the theoretical basis for exploiting the clinical application of chaetocin in cancer treatment.

The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture

Previous studies have proved that dynamic culture could facilitate nutrients transport and apply mechanical stimulation to the cells within three-dimensional scaffolds,thus enhancing the differentiation of stem cells towards the osteogenic phenotype.However,the effects of macropore size on osteogenic differentiation of stem cells under dynamic condition are still unclear.Therefore,the objective of this study was to investigate the effects of macropore size of hydroxyapatite(HAp)scaffolds on osteogenic differentiation of bone mesenchymal stem cells under static and perfusion culture conditions.In vitro cell culture results showed that cell proliferation,alkaline phosphate(ALP)activity,mRNA expression of ALP,collagen-I(Col-I),osteocalcin(OCN)and osteopontin(OPN)were enhanced when cultured under perfusion condition in comparison to static culture.Under perfusion culture condition,the ALP activity and the gene expression of ALP,Col-I,OCN and OPN were enhanced with the macropore size decreasing from 1300 to 800 mm.However,with the further decrease in macropore size from 800 to 500 mm,the osteogenic related gene expression and protein secretion were reduced.Computational fluid dynamics analysis showed that the distribution areas of medium-and high-speed flow increased with the decrease in macropore size,accompanied by the increase of the fluid shear stress within the scaffolds.These results confirm the effects of macropore size on fluid flow stimuli and cell differentiation,and also help optimize the macropore size of HAp scaffolds for bone tissue engineering.

生长分化因子-5(GDF-5)促进人退行性变髓核细胞外基质表达情况的研究（英文）

目的：研究腺病毒介导的GDF-5对人退行性变椎间盘髓核细胞生长和细胞外基质表达的影响，探索椎间盘退行性变基因治疗的新途径。创新点：首次验证了GDF．5对人退行变的髓核细胞的生长和细胞外基质的分泌均具有明显的促进作用，为椎间盘退行性变疾病早期基因治疗提供了新的途径。方法：利用腺病毒介导的GDF．5转染人退变的髓核细胞，设空白对照组、阴性对照组（绿色荧光蛋白（GFP）组）和实验组（GDF-5组）三个组，3、7、14和21天四个时问点。在预定的时间点，通过蛋白质免疫印迹（Westernblotting）、番红-O染色、免疫组化染色、酶联免疫法定量检测（ELISA）、逆转录聚合酶链式反应（RT-PCR）和细胞外基质的定量分析等手段，验证GDF-5对退变髓核细胞外基质表达的影响，同时对GDF．5对髓核细胞生长情况的促进作用进行了表征。结论：Ad—GDF-5能成功转染人退变的髓核细胞（图1），能有效地促进人退变髓核细胞细胞外基质Aggreean和Ⅱ型胶原（CollagenⅡ）分泌（图4-7），RT-PCR的结果表明Aggrecan和CollagenII基因表达也得到了明显的增强（图8）。同时GDF-5对人退变的髓核细胞的生长也有一定的促进作用（图9）。因此，Ad-GDF-5是椎间盘退行性变早期基因治疗的新途径。

新型壳聚糖水凝胶结合软骨细胞修复兔关节软骨缺损的实验研究(英文)

目的：评估壳聚糖水凝胶结合肋软骨细胞构建的新型组织工程软骨对兔关节软骨缺损的修复效果。创新点：利用自主研发的具有良好生物相容性和稳定性的壳聚糖水凝胶与软骨细胞，在体外初步构建组织工程软骨，并尝试利用其修复缺损的关节软骨，从而为关节软骨缺损的修复提供了一种新的治疗方法。方法：取兔肋软骨体外培养扩增，获得P2代软骨细胞，将其种植到冻干的壳聚糖水凝胶上，体外培养一周，获得初步构建的组织工程软骨。构建兔膝关节软骨缺损模型，并分为3组：实验组植入组织工程软骨；对照组植入壳聚糖水凝胶；空白组不做任何处理。分别于术后4、8和12周取材，通过大体观察、苏木精．伊红染色、番红-O染色及Ⅱ型胶原免疫组化染色等方法观察缺损关节软骨的修复情况，并用国际关节软骨修复协会（ICRS）制定的评分法进行大体及组织学评分。结论：兔肋软骨细胞能在实验室自主构建的壳聚糖水凝胶上增殖并分泌细胞外基质（图2），植入到兔关节软骨缺损处后，对缺损关节软骨具有良好的修复作用（图3和5），且修复是一种完全的结构性的修复（图5～7）。

携载生长分化因子5质粒的壳聚糖-透明质酸-硫酸软骨素微球在骨关节炎基因治疗中的应用（英文）

目的:骨关节炎是临床上的一种常见病和多发病。本研究尝试利用壳聚糖、透明质酸和硫酸软骨素为载体,制备一种携载生长分化因子5(GDF-5)质粒的纳米微球用于骨关节炎的基因治疗。创新点:首次利用壳聚糖、透明质酸、硫酸软骨素三种原料制备可携载GDF-5质粒的三元纳米微球,并将其应用到骨关节炎的治疗中。方法:在55°C下,按不同比例混合壳聚糖、透明质酸钠、硫酸软骨素和GDF-5质粒,利用静电吸附原理制备携载GDF-5质粒的三元纳米微球。分别利用扫描电镜和激光粒度散射仪测试微球的形貌和粒径;利用凝胶电泳检测质粒与微球的结合情况;利用CCK-8检测微球的细胞毒性。将携载GDF-5质粒的微球与软骨细胞共培养,并将脂质体和空载组作为对照组,在预定的时间点通过免疫荧光染色、免疫组化染色以及生化成分分析,观察微球对软骨细胞外基质分泌情况的影响。最后将该纳米微球注射到骨关节炎模型兔体内,通过大体观察、苏木精-伊红(H&E)染色、免疫荧光染色和免疫组化分析该微球对骨关节炎的作用。结论:本研究成功地利用壳聚糖、透明质酸和硫酸软骨素为原料,制备出携载GDF-5质粒的纳米微球。其中GDF-5质粒可以有效地促进软骨细胞外基质的分泌,透明质酸和硫酸软骨素是临床上常见的治疗骨关节炎的药物。微球具有良好的理化性能,其细胞毒性小,转染效率高,在体内外均能有效地促进软骨细胞外基质的分泌,能够在一定程度上延缓骨关节炎的进展。该纳米微球将是一种极具希望的可应用于骨关节炎基因治疗的载体。