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61.

Background

Mesenchymal stromal cell (MSC)–based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.

Methods

Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model.

Results

The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5?×?106) and low (0.5?×?106) cell-injected groups. Injection of 2.5?×?106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5?×?106 constitutive IL-4 or NFκB-sensing IL-4–secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFκB-sensing IL-4–secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)α and IL-1β secretion were observed between the MSC-transplanted and control groups in the explant culture.

Discussion

Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4–secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.  相似文献   
62.
Effect of Magnetic Field on Chick Morphogenesis   总被引:1,自引:0,他引:1  
It is well known that development of organisms, as well as normal functioning of different systems, is to a large extent affected by environmental factors. To study the effect of magnetic field on the chick morphogenesis, fresh fertilized eggs of White Leghorn were incubated to the definitive primitive streak stage [Hamburger-Hamilton (H.H.) stage 4]. The embryos were mounted on a watch glass using News in vitro culturing technique and then exposed to a homogeneous magnetic field of 5000 ± 200 Oe for 1 h. The controls were maintained simultaneously without the magnetic field. The experimental and control embryos were further incubated for 24 h so as to obtain the H.H. stage 12 in the controls. It was observed that experimental embryos were considerably retarded, as evidenced by shortening of the embryonic long axis and by other malformations. In 14 out of the 25 experimental embryos, the brain was poorly developed with open neural tube. In 18 of the 25 experimental embryos, the somites were diffused, and in 12 of the 25 experimental embryos, the heart was developed with slight displacement. All the controls developed normal to H.H. stage 12. Histological observations of the neural structures in the sectioned experimental embryos show increase in the number of dividing cells and their dispersed distribution throughout the neuroepithelium. The malformations recorded are attributed to the environmental stress effect caused by the magnetic field as manifested by its effect on mitotic activity, interkinetic nuclear migration in neuroepithelium and cell locomotion in general.  相似文献   
63.
  1. The "glucose-bleached" cells of Chlorella protothecoides, whichwere obtained by the method described previously, were transferredto a glucose-free medium containing basal mineral nutrientsalone in the dark, and after a certain period of time, the cellsuspension was supplied with urea and light to induce the greeningof cells. At different times before and after the provisionof urea and light, the inhibitors were applied to the cultureto test their effects upon the process of greening.
  2. Markedgreening of the glucose-bleached cells occurred aftera lagperiod in the control culture. 5-Fluorouracil inhibitedthecell greening strongly when it was applied at differenttimesbefore the provision of urea and light. When applied aftertheprovision of urea and light, the suppressive effect of 5-fluorouracilgradually decreased with the delay of its application. No inhibitiveeffect was observed when the uracil analogue was added laterthan the 12th hr after the provision of urea and light, thetime around which the chlorophyll formation started in the controlculture. On the other hand, the cell division was much morestrongly affected by 5-fluorouracil. Even when it was appliedat the 18th hr after the provision of urea and light, the celldivision was completely halted, indicating that the greeningand division of the glucose-bleached cells are separate processes.Different mechanisms of action of the uracil analogue towardsthese two processes were suggested.
  3. Dihydrostreptomycin showedits strongest suppressive effectwhen added at the beginningof the dark incubation of algalcells in the glucose-free medium,and with the delay of application,its effect was progressivelyreduced, even during the periodof the dark incubation. Thesuppression, however, was stillmarked when it was applied atthe 15th hr.
  4. Chloramphenicol was found to inhibit stronglythe chlorophyllformation and protein synthesis, but, to a muchlesser extent,RNA synthesis. Acridine orange suppressed thecell greeningand division at such a low concentration as 1.5µg/ml.
  5. Based on these observations it was concludedthat synthesesof nucleic acid and protein are essential processesfor thegreening of the glucose-bleached algal cells. Successiveeventsoccurring in the greening process were discussed.
(Received March 9, 1965; )  相似文献   
64.
Electrophoretic studies of the enzymes produced by sixty-four independently derived hybrid clones have made possible the detection of autosomal linkages on human chromosomes.  相似文献   
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Although environmental factors are important, there is considerable evidence that genes also have a significant role in the pathogenesis of obesity. We conducted a population-based study to investigate the relationship between candidate genes for obesity (UCP1, UCP2, ADRA2B, ADRB3, LEPR, VDR and ESR1) and adiposity measures (body mass index, body fat percentage, weight, waist circumference and waist–hip ratio) in terms of individual gene and gene × gene interaction in models unadjusted and adjusted for covariates (age, years since menopause, educational level and total energy intake). Postmenopausal women with TC genotype of ESR1 gene had higher body fat percentage than those with TT genotype in the models unadjusted and adjusted for the covariates (P = 0.006 in adjusted model). In multiple logistic regression analysis, BsmI and ApaI SNPs of VDR genes were significantly associated with overweight and obesity. The UCP2–VDR ApaI interaction to susceptibility of overweight and obesity was first observed from logistic regression analysis, and then confirmed in the multifactor dimensionality reduction method unadjusted and adjusted for the covariates. This interaction had 69.09% prediction accuracy for overweight and obesity (P = 0.001, sign test). In conclusion, the study suggests the significant association of ESR1 and VDR genes with adiposity measures and the UCP2VDR ApaI interaction to susceptibility to being overweight and obesity in postmenopausal Vietnamese women.  相似文献   
70.
RNA metabolism of Indian rice grass seeds was studied in relation to imbibition and germination. These seeds germinate only after scarification of the seed coats. The hard seed coats restrict germination but not water intake or changes in the quantity and quality of RNA formed during early hours of soaking. These changes differ markedly from those in scarified (H2SO4 treated) seeds which are able to germinate. Gibberellic acid hastens germination of scarified seeds and causes changes in the population of RNA transcribed.  相似文献   
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