大鼠脂肪干细胞定向分化为成骨细胞及体外增殖过程中地塞米松的抑制性干预

背景:不同浓度的地塞米松在体外诱导脂肪千细胞向成骨细胞分化过程中所起的作用是不同的,其作用机制尚不明确.目的:验证脂肪干细胞向成骨细胞分化的能力,观察成骨细胞分化早期不同浓度地塞米松对脂肪干细胞体外增殖的抑制效果.设计、时间及地点:细胞学体外观察,于2008-01/03在南方医科大学组织工程研究中心完成.材料:5周龄雄性SD大鼠10只,由南方医科大学实验动物中心提供.地塞米松为Sigma公司产品.方法:切取大鼠腹股沟皮下脂肪组织,用酶消化法分离培养脂肪干细胞,传至第3代后,加入条件培养液(含胎牛血清、维生素C、β-甘油磷酸钠、青霉素、链霉素的DMEM高糖完全培养基)进行体外预培养.设立2组:地塞米松组分别于细胞传代后第0,2,4天向培养基中加入10-6mol/L地塞米松1mL,空白对照组仅加入等量条件培养液.主要观察指标:倒置显微镜下观察细胞生长及成骨分化情况.采用MTT比色法检测细胞增殖情况.结果:①原代培养中贴壁细胞多数呈长梭形,少数呈小圆形或三角形,六七天后进行传代;传代后细胞生长速度较原代细胞明显增快,至第15代细胞仍未出现明显衰老现象;第3代细胞在加入地塞米松后逐渐呈均一的长梭形,随时间延长呈叠形多层排列,细胞外基质明显增多,并逐渐形成多个小结样结构.空白对照组细胞形态不一,部分细胞呈多边形或三角形,细胞外基质明显少于地塞米松组,罕见小结样结构.②在体外传代培养过程中,空白对照组脂肪干细胞能够保持持续分裂增殖的能力.与空白对照组比较,细胞传代培养后0,2 d加入地塞米松,干预6,8,10,12 d时细胞数量均明显下降(P<0.05);传代培养后4 d加入地塞米松,干预6,8,10,12 d时细胞数量无明显变化(P>0.05).结论:传代的脂肪干细胞经地塞米松处理后,细胞形态趋于成熟,生长速度减慢,可定向分化为成骨细胞.在向成骨细胞分化早期,地塞米松能够抑制脂肪干细胞的体外增殖.     

免疫耐受性树突状细胞在移植免疫中的作用及其分子机制

新的研究发现一种半成熟树突状细胞亚群,其高表达主要组织相容性复合体II、中等表达CD40、CD80和CD86等分子,在自身免疫性疾病中表现出诱导免疫耐受的潜能,其与未成熟树突状细胞一道被认为是致耐受细胞.这使过去将树突状细胞分为未成熟和成熟两种类型的概念受到挑战.但是,它们在移植免疫中的具体作用和机制仍未完全明了.文章对致耐受树突状细胞的体内迁移过程、在移植免疫中分子机制和体外获得等方面的最新进展进行综合分析和热点追踪,为进一步理解和研究致耐受树突状细胞在移植免疫反应中的作用拓宽视野.     

In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles

AIM： To synthesize antisense oligonucleotides （ASODNs） of midkine （MK）, package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma （HCC） growth using these nanoparticles. METHODS： HepG2 cell proliferation was analyzed in vitro using the 3-（4,5-dimethythiazol-2-yl）-5- （3-carboxymethoxyphenyl）-2-（4-sulfophenyl）- 2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction （PCR）. RESULTS： The in vitro proliferation of HepG2 cells was significantly inhibited by the nanoparticles packaged with MK-ASODNs （NANO-ASODNs）. Furthermore, the NANOASODNs significantly inhibited the growth of HCC in the mouse model. CONCLUSION： NANO-ASODNs can significantly suppress the growth of HCC in vitro and in vivo.     

Mathematical modelling of glycosaminoglycan production by stem cell aggregates incorporated with growth factor‐releasing polymer microspheres

Systems composed of high density cells incorporated with growth factor‐releasing polymer microspheres have recently been shown to promote chondrogenic differentiation and cartilage formation. Within these systems, the effects of spatial and temporal patterning of growth factor release on hyaline cartilage‐specific extracellular matrix production have been examined. However, at present, it is unclear which microsphere densities and growth factor delivery profiles are optimal for inducing human mesenchymal stem cell differentiation and glycosaminoglycan production. A mathematical model to describe glycosaminoglycan production as a function of initial microsphere loading and microsphere degradation rate over a period of 3 weeks is presented. Based on predictions generated by this model, it may be feasible to design a bioactive microsphere system with specific spatiotemporal growth factor presentation characteristics to promote glycosaminoglycan production at controllable rates. Copyright © 2014 John Wiley & Sons, Ltd.     

Surgical outcome evaluation of perforated gastric cancer: from the aspects of both acute care surgery and surgical oncology

Background: Perforated gastric cancer (PGC) is a rare condition of gastric cancer (GC). In this study, we sought to assess the outcome of PGC from the aspects of both acute care surgery and surgical oncology at a single institute, Chang Gung Memorial Hospital (CGMH).

Methods: From 1997 to 2013, 6864 patients were diagnosed with GC and 2738 were diagnosed with gastroduodenal perforation at CGMH. In total, 29 patients with PGC were identified. Immediate surgical and long-term oncologic outcomes were evaluated after an appropriate matching process was performed.

Results: The immediate surgical outcome of PGC, i.e., the hospital mortality rate within 30 d after surgery, did not significantly differ from that of non-cancer related gastroduodenal perforation. The long-term oncologic outcome, with matching by age, gender, year of surgery and AJCC 7th stage grouping, also did not significantly differ from that of GC without perforation.

Conclusions: Aggressive surgical treatment, including an initial emergency procedure for containing peritonitis and radical surgery for GC, may benefit PGC patients in terms of both the immediate and oncologic outcomes.     

Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF,and CX3CL1 genes as hypomethylated in osteoarthritis

Clinical Rheumatology - The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation...     

Acute psychoactive and toxic effects of D. metel on mice explained by 1H NMR based metabolomics approach

Metabolic Brain Disease - Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious...     

Protein Quality Control Dysfunction in Cardiovascular Complications Induced by Anti-Cancer Drugs

Cardiovascular complications, including heart failure, hypertension, ischemic syndromes and venous thromboembolism, have been identified in patients treated with anti-cancer drugs. Oxidative stress, mitochondrial dysfunction and DNA synthesis inhibition are considered to be responsible for the cardiotoxicity induced by these agents. Protein quality control (PQC) has 3 major components, including the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, and participates in protein folding and degradation to maintain protein homeostasis. We have demonstrated that PQC dysfunction is a new causal mechanism for the development of cardiac hypertrophy and failure. Increasing evidence shows that anti-cancer drugs, such as tyrosine kinase inhibitors, proteasome inhibitors, anthracyclines and autophagy inhibitors, cause PQC dysfunction. Here, we provide an overview of the potential role of PQC dysfunction in the development of cardiovascular complications induced by anti-cancer drugs.