Various treatment methods for tracheal defects have been attempted, such as artificial implants, allografts, autogenous grafts, and tissue engineering; however, no perfect method has been established. We attempted to create an effective artificial trachea via a tissue engineering method using 3D bio-printing. A multi-layered scaffold was fabricated using a 3D printer. Polycaprolactone (PCL) and hydrogel were used with nasal epithelial and auricular cartilage cells in the printing process. An artificial trachea was transplanted into 15 rabbits and a PCL scaffold without the addition of cells was transplanted into 6 rabbits (controls). All animals were followed up with radiography, CT, and endoscopy at 3, 6, and 12 months. In the control group, 3 out of 6 rabbits died from respiratory symptoms. Surviving rabbits in control group had narrowed tracheas due to the formation of granulation tissue and absence of epithelium regeneration. In the experimental group, 13 of 15 animals survived, and the histologic examination confirmed the regeneration of epithelial cells. Neonatal cartilage was also confirmed at 6 and 12 months. Our artificial trachea was effective in the regeneration of respiratory epithelium, but not in cartilage regeneration. Additional studies are needed to promote cartilage regeneration and improve implant stability.
Abstract. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer insensitive to chemotherapy. Efforts are, therefore, directed toward understanding the molecular mechanisms of chemotherapy insensitivity and the development of new anticancer drugs. Ginsenoside Rh2, one of the components in ginseng saponin, has been shown to have anti-proliferative effect on human NSCLC cells and is being studied as a therapeutic drug for NSCLC. microRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in cancer progression and prevention. However, the miRNA portrait of ginsenoside Rh2-treated NSCLC cells has not yet been studied. In this study, we identified a unique set of changes in the miRNA expression profile in response to Rh2 treatment in the human NSCLC cell line A549. Using miRNA microarray analysis, we identified 44 and 24 miRNAs displaying changes in expression greater than 2-fold in Rh2-treated A549 cells. In addition, using an miRNA target prediction program, we discovered that these miRNAs are predicted to have several target genes related to angiogenesis, apoptosis, chromatic modification, cell proliferation and differentiation. Thus, these results may assist in the better understanding of the anticancer mechanism of Rh2 in NSCLC.
How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21 WAF1 , a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2-dependent Slug degradation and that this p53 function is mimicked by p53 R273H , a mutant lacking trans-activating activity. These actions of p21 and p53 are induced by c-irradiation of cells and also operate in vivo. This is the first study to elucidate a mechanism involving p53 and p21 cooperation.
Tracheal resection has limited applicability. Although various tracheal replacement strategies were performed using artificial prosthesis, synthetic stents and tissue transplantation, the best method in tracheal reconstruction remains to be identified. Recent advances in tissue engineering enabled 3D bioprinting using various biocompatible materials including living cells, thereby making the product clinically applicable. Moreover, clinical interest in mesenchymal stem cell has dramatically increased. Here, rabbit bone marrow-derived mesenchymal stem cells (bMSC) and rabbit respiratory epithelial cells were cultured. The chondrogenic differentiation level of bMSC cultured in regular media (MSC) and that in chondrogenic media (d-MSC) were compared. Dual cell-containing artificial trachea were manufactured using a 3D bioprinting method with epithelial cells and undifferentiated bMSC (MSC group, n = 6) or with epithelial cells and chondrogenic-differentiated bMSC (d-MSC group, n = 6). d-MSC showed a relatively higher level of glycosaminoglycan (GAG) accumulation and chondrogenic marker gene expression than MSC in vitro. Neo-epithelialization and neo-vascularization were observed in all groups in vivo but neo-cartilage formation was only noted in d-MSC. The epithelial cells in the 3D bioprinted artificial trachea were effective in respiratory epithelium regeneration. Chondrogenic-differentiated bMSC had more neo-cartilage formation potential in a short period. Nevertheless, the cartilage formation was observed only in a localized area.
The recent explosion of publicly available biology gene sequences and chemical compounds offers an unprecedented opportunity for data mining. To make data analysis feasible for such vast volume and high-dimensional scientific data, we apply high performance dimension reduction algorithms. It facilitates the investigation of unknown structures in a three dimensional visualization. Among the known dimension reduction algorithms, we utilize the multidimensional scaling and generative topographic mapping algorithms to configure the given high-dimensional data into the target dimension. However, both algorithms require large physical memory as well as computational resources. Thus, the authors propose an interpolated approach to utilizing the mapping of only a subset of the given data. This approach effectively reduces computational complexity. With minor trade-off of approximation, interpolation method makes it possible to process millions of data points with modest amounts of computation and memory requirement. Since huge amount of data are dealt, we represent how to parallelize proposed interpolation algorithms, as well. For the evaluation of the interpolated MDS by STRESS criteria, it is necessary to compute symmetric all pairwise computation with only subset of required data per process, so we also propose a simple but efficient parallel mechanism for the symmetric all pairwise computation when only a subset of data is available to each process. Our experimental results illustrate that the quality of interpolated mapping results are comparable to the mapping Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. To copy otherwise, to republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. HPDC '10 Chicago, Illinois USA Copyright 2010 ACM X-XXXXX-XX-X/XX/XX ...$10.00. results of original algorithm only. In parallel performance aspect, those interpolation methods are well parallelized with high efficiency. With the proposed interpolation method, we construct a configuration of two-million out-of-sample data into the target dimension, and the number of out-of-sample data can be increased further.
Transdermal delivery systems have been intensively studied over the past 2 decades, with the focus on overcoming the skin barrier for more effective application of pharmaceutical and cosmetic products. Although the cosmeceutical industry has made a substantial progress in the development and incorporation of new and effective actives in their products, the barrier function of the skin remains a limiting factor in the penetration and absorption of these actives. Enhancement via modification of the stratum corneum by hydration, acting of chemical enhancers on the structure of stratum corneum lipids, and partitioning and solubility effects are described. This review summarizes the advances in the development and mechanisms of action of chemical components that act as permeation enhancers, as well as the advances in appropriate vehicles, such as gels, emulsions, and vesicular delivery systems, that can be used for effective transdermal delivery.
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