lncRNA/miRNA在胰腺癌发生发展中的研究进展

ncRNA/miRNA在多种实体肿瘤中表达异常，参与肿瘤的增殖、侵袭、转移。胰腺癌是发病率较高、死亡率高的恶性肿瘤，通过深入研究lncRNA/miRNA在胰腺癌发生发展中的分子机制，可为胰腺癌的治疗提供新的靶点。     

Extracellular Enzyme Activities by Basidiobolus and Conidiobolus Isolates on Solid Media./Extrazelluläre Enzymaktivitäten bei Basidiobolus- und Condiobolus-Isólaten auf festen Medien

Summary: Fifty-seven isolates of Basidiobolus from reptiles and amphibians, and 7 other obtained from the American Type Culture Collection (ATCC) in Maryland were studied for their extracellular enzyme activities on solid media. The Conidiobolus isolates studied included 4 recovered from Nigerian soil and additional 4 obtained from the ATCC All these isolates produced active extracellular lipase and protease and failed to exhibit amylase, deoxyribonuclease and ribonuclease activities. The significance of the findings is discussed.
Zusammenfassung: Fünfundsiebzig Basidiobolus-Isolate aus Reptilien und Amphibien und sieben weitere aus der American Type Culture Collection (ATCC) in Maryland wurden auf Aktivtäten extrazellulärer Enzyme auf festen Medien untersucht Die untersuchten Conidiobolus-Isolate schlossen vier aus nigerianischen Böden und vier weitere aus der ATCC ein. Alle Isolate zeigten extrazellulär Lipase- und Proteaseaktivität Amylase-, Desoxyribonuclease- und Ribonucleaseaktivität war jedoch nicht nachzuweisen. Die Bedeutung dieser Befunde wird diskutiert.     

角膜基质细胞体外长期培养过程中生物学特性的改变

目的 研究兔角膜基质细胞在体外长期培养传代过程中,细胞增殖能力和胞外基质表达水平的改变。方法 取体外培养兔角膜基质细胞,由光镜对各代细胞的形态学变化进行观测。通过对各代细胞生长曲线的绘制,得出其各自的群体倍增时间;MTT法比较各代细胞增殖能力的改变。RT-PCR和Western杂交检测各代细胞中Ⅰ、Ⅲ型胶原表达水平的改变;爱茜蓝法检测糖胺聚糖(GAG)的含量。结果 体外培养兔角膜基质细胞随着传代的进程,逐渐显现衰老的形态特征。细胞群体倍增时间由第7代起显著延长(P<0.01);MTT比色法的结果亦显示,第7代细胞的增殖能力开始大幅下降(P<0.01)。第9-11代时,Ⅰ、Ⅲ型胶原在mRNA和蛋白水平的表达都有明显减少(P<0.01),降至第1代细胞的30％左右;GAG的含量也降至40％左右。结论 兔角膜基质细胞经历长期体外培养后,细胞增殖能力和胞外基质表达水平显著下降,逐渐丧失原有的功能。但作为构建组织工程化角膜的种子细胞,在它的生物学特性未发生改变之前,经3次传代培养,获取的细胞量达到组织块消化所得细胞的240倍左右,已足以用于构建之用。     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

Antisense Smad2 inhibits high glucose-stimulated production of extracellular matrix in cultured rat glomerular mesangial cells

Transforminggrowthfactor-β1(TGF-β1)is amultifunctionalpolypeptidethatregulatesanum-berofcellularprocesses,includingcellprolifera-tion,differentiation,apoptosis,migration,matrix synthesis,andtheimmuneresponse[1,2].Inchron-icrenaldiseases,TGF-β1isakeymediatorofex-tracellularmatrix(ECM)accumulation[3].Oneof thetargetrenalcellsforTGF-β1isglomerular mesangialcellsthatarecapableofproducingcom-ponentsofECM,suchascollagens,lamininand fibronectin[4,5].Recentstudiesindicatedthatinhi-bitionofT…     

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

RELAXATION OF MESENTERIC ARTERY OF STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS BY CALCIUM REMOVAL

1. The time courses of the relaxation, induced by removal of extracellular Ca2+, of K-depolarized mesenteric artery preparations from stroke prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were compared. 2. The time course of the decline in extracellular Ca2+ was estimated from the time course of the relaxation and the concentration-response curve of K(+)-depolarized preparations to Ca2+. The time course of the decline in the intracellular free Ca2+ concentration was also estimated from the reported relation between Ca2+ concentration and the contraction of skinned vascular smooth muscle. 3. The time course of relaxation was exponential, the curve being made up of three components. The time course was slower in preparations from SHRSP, especially the first component of the relaxation curve. 4. The time courses of the decline in the intracellular and extracellular Ca2+ concentrations were also exponential, being made up of three components and were also slower in the preparation made from SHRSP. 5. The wall and muscle layer of the mesenteric arteries used in the present experiments were significantly thicker in the SHRSP preparations. 6. Calculation of the half relaxation time, based on the diffusion of Ca2+ across the blood vessel wall, suggested that the slower relaxation in preparations from SHRSP is due largely to the thicker muscle layer, although differences in Ca2+ sequestration by the smooth muscle cells may also be involved.     

Effects of immunosuppressors and cytostatics on the extracellular matrix production in experimental nephropathy

Methylprednisolone increased the content of laminine, cyclosporin increased the content of fibronectin, and cyclophosphamide suppressed the extracellular matrix production in experimental nephrotoxic nephritis and puromycin aminonucleoside nephrosis. Therapy should be chosen with due consideration of the extracellular matrix structure in different morphological variants of chronic glomerulonephritis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 584–587, November, 1998