121 research outputs found
From the Eyes to the Suffering Brain: Can Eye Tracking be Considered as a Significant Digital Biomarker for Neurological Diseases?
No full textChondrogenic differentiation of mouse induced pluripotent stem cells (iPSCs) using the 3 three-dimensional culture with ultra-purified alginate gel (UPAL gel)
No full textAs articular cartilages have rarely healed by themselves because of their characteristics of avascularity and low cell density, surgical intervention is ideal for patients with cartilaginous injuries. Because of structural characteristics of the cartilage tissue, a three-dimensional culture of stem cells in biomaterials is a favorable system on cartilage tissue engineering. Induced pluripotent stem cells (iPSCs) are a new cell source in cartilage tissue engineering for its characteristics of self-renewal capability and pluripotency. However, the optimal cultivation condition for chondrogenesis of iPSCs is still unknown. Here we show that a novel chondrogenic differentiation method of iPSCs using the combination of three-dimensional cultivation in ultra-purified alginate gel (UPAL gel) and multi-step differentiation via mesenchymal stem cell-like cells (iPS-MSCs) could efficiently and specifically differentiate iPSCs into chondrocytes. The iPS-MSCs in UPAL gel culture sequentially enhanced the expression of chondrogenic marker without the upregulation of that of osteogenic and adipogenic marker and histologically showed homogeneous chondrogenic extracellular matrix formation. Our results suggest that the pluripotency of iPSCs can be controlled when iPSCs are differentiated into iPS-MSCs before embedding in UPAL gel. These results lead to the establishment of an efficient three-dimensional system to engineer artificial cartilage tissue from iPSCs for cartilage regeneration. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1086-1093, 2019
Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis
No full textCaveolin-1 is an essential component of membrane caveolae. It is an important regulator of cellular processes such as signal transduction and endocytosis. We report here, for the first time, that caveolin-1 is a target of the K-RAS oncogene in colon carcinogenesis. Caveolin-1 is induced in colon cancer cells and in human colon tumor samples, in response to K-RAS activating mutations. An activated K-RAS oncogene transcriptionally induces caveolin-1 expression in human colon cancer cells and this effect is not restricted to the type of activating K-RAS mutation. Inhibition of the P-I3 Kinase-AKT pathway, but not the ERK MAPK pathway, both important K-RAS effectors, leads to a decrease in caveolin-1 expression indicating that the AKT pathway is involved in caveolin-1 expression in response to an activated K-RAS. Increased AKT signaling induces caveolin-1 expression by increasing the activity of the transcription factor, Sp1. Interestingly; caveolin-1 depletion alters K-RAS-dependent signaling by decreasing Grb2-SOS activity. Consistent with these finding, caveolin-1-depleted cells shows decreased migration in vitro. However, caveolin-1 overexpression by itself does not increase migration whereas an activated Src can increase migration in a caveolin-1-dependent manner. This increased migration is highly dependent on the RhoA GTPase, indicating that an activated K-RAS modulates migration in part via caveolin-1 induction, and increasing RhoA activity via phospho-caveolin-1. Our findings indicate that K-RAS regulates both caveolin-1 expression and other factors affecting caveolin-1 functions in colon cancer-derived cell migration. What's new? The role of the membrane protein caveolin-1 in cancer development has been a subject of controversy. Here the authors report, for the first time, that caveolin-1 is a target of the K-RAS oncogene in colon carcinogenesis. They demonstrate that caveolin-1 is induced in response to mutant K-RAS through AKT activation in colon cancer. They also identify caveolin-1 as a novel activator of K-RAS-dependent signaling and cancer cell migration. The data suggest that caveolin-1 is a conditional "oncogene" in colon cancer whose activity depends on mutant K-RAS, and that a positive feedback loop exists between K-RAS-dependent caveolin-1 expression and signaling. Copyright © 2012 UICC
Hydrometallurgical treatment of lead blast furnace slag
No full textThe replacement of traditional smelting processes in the non-ferrous smelter industry, with new energy efficient and environmentally acceptable processes, combined with the need to maximize recoveries, has increased the need for slag treatment. Several approaches are available on a commercial basis, and the selection of any one approach will depend on a number of factors. This research deals with a novel, hydrometallurgical approach to recovering the primary non ferrous metal values from lead blast furnace slag.
The results have illustrated that a two stage leach is necessary for recovering the zinc and lead from the slag. This two stage leach produced a zinc/iron solution and a lead solution and the former was then treated by solvent extraction which was aimed at separating the zinc and the iron present in the leach liquor. This separation was enhanced by using metallic zinc as a reductant in a low concentration sulfuric acid strip solution to reduce and strip the ferric iron from Di (2 - ethylhexyl) phosphoric acid which was used as the solvent extractant. The effects of temperature, acid concentration, ultrasound leaching, extractant concentration, pH, stripping time, stripping volume, phase ratio and nitrogen sparging were examined. An optimum set of process conditions for maximizing the zinc concentration in the pregnant solution has been determined --Abstract, page iv
Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs
No full textBackground: Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. Methods: Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. Findings: Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. Interpretation: These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. Funding: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/
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Regulation and Function of Caveolin-1 in Colorectal Carcinogenesis
No full textColon cancer is the second leading cause of cancer deaths in the United States of America. It is caused by the accumulation of mutations in tumor suppressors and oncogenes. The APC tumor suppressor is mutated in most diagnosed cases of colorectal cancer. Mutations in the K-RAS oncogene occur at later stages of colon cancer progression. In the present study, the transcriptional regulation of a novel target of these two genes, caveolin-1, was studied. Caveolin-1 is transcriptionally regulated by the APC tumor suppressor gene, via induction of its inducer, FOXO1 and the suppression of its transcriptional repressor, C-MYC. An activated K-RAS oncogene induces caveolin-1 transcription via activation of the P-I3 Kinase pathway. In addition to transcriptional regulation of caveolin-1, the influence of caveolin-1 expression on cellular phenotypes like signal transduction and polyamine uptake were assessed. The present studies demonstrate that caveolin-1 expression affects basal levels of AKT and ERK signaling, with an increased signaling associated with caveolin-1 expression in these colon tumor-derived cells. In addition, caveolin-1 expression positively affects signaling in response to an inflammatory stimulus like TPA. Interestingly, caveolin-1 expression leads to a decrease in the uptake of pro-tumorigenic molecules like polyamines, in the colon cell lines tested. Taken together, the data from this study suggests that caveolin-1 is transcriptionally regulated by the APC and the K-RAS gene at different stages of colorectal tumorigenesis and this in turn, leads to different phenotypes influenced by caveolin-1 expression
HIV Infection and Adipose Tissue Resident Stem Cells: Their Involvement in Pathology and Treatment
No full textApplication of Polymeric Nanoparticles for Brain Targeting
No full textNanocarrier holds a widespread application in drug targeting and effective delivery to the desired site for the treatment of numerous disease conditions. Reaching the brain is truly arduous for the therapeutic moieties due to the BBB and other protective measures. A series of diverse nanocarrier systems and novel approaches have been explored to deliver bioactives to the brain effectively. Polymeric nanoparticles embrace significant capabilities for effective brain delivery by virtue of the unique characteristics of individual polymers. Chitosan, PLGA, alginate, PEG, PAMAM, etc., and their inimitable combinations or derivatives, are often used for brain targeting. The characteristic features of these polymers and nanosize facilitate the permeation of the drug-carrier system through BBB by various mechanisms like enhanced permeation, passive diffusion, active transport via receptor-mediated endocytosis, or carrier-mediated transcytosis. The surface flexibility allows the enhanced targeting via surface decoration with specialized moieties for definite functions such as PEG for stealth nature and protects from the RES system. Antibodies, high-molecular-weight proteins, and peptides and ligands against cell surface receptors like GLUT, transferrin, and lactoferrin promote carrier or receptor-mediated transport. At the same time, drug release in a controlled manner assures the therapeutic activity for prolonged duration and limits drug clearance. This chapter highlights the application of polymeric nanoparticles for brain targeting with special emphasis on various types of polymers suitable for brain delivery, including natural and synthetic polymers, methods of synthesis of polymeric nanoparticles, brain targeting approaches, and toxicological aspects
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