Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the biological characteristics of human bone marrow mesenchymal stem cells from bone marrow of different age donors. The experiments were divided into four groups by donors age, group A represented MSC derived from fetal bone marrow, group B represented MSC derived from bone marrow of 0-20 years old donors, group C represented MSC derived from bone marrow of 20-40 years old donors and group D represented MSC derived from bone marrow of donors older than 40. The growth, purification, proliferation and multipotential abilities of MSC in 4 groups were observed and their immunophenotypes were determined by flow-cytometry. The level of cytokines (IL-6, SCF, FLT-3L, SDF-1 and TGF-beta1) were assayed by ELISA method. Cell cycles were analyzed to show the proliferation index (PrI). MSCs derived from bone marrow of 4 groups were injected subcutaneous into NOD/SCID mouse to observe the safety. The results showed that different age donors bone marrow all gave rise to MSC. These cells were similar in morphology, antigenic phenotype, differentiation potential and cell cycle. The primary culture time of group B was shorter than other groups. The duration of passage 1 (P1) was 5.5 days, and the duration of P10 was 33 days, after P10 culture, (5.19 +/- 2.15) x 10(10) MSCs were obtained from 8 x 10(6) MNC of this group. The primary culture time of groups A, C, D were longer, the duration of P1 were 15, 7 and 13 days for group A, C and D respectively, and the duration of P10 was 50, 60 and 72 days for group A, C and D, respectively. After P10 culture, (4.98 +/- 2.08) x 10(10), (1.86 +/- 0.47) x 10(10), (0.64 +/- 0.22) x 10(10) MSCs were obtained from 8 x 10(6) MNC of group A, C and D respectively. The morphology of MSC of group A was longer and slender. The ability of expansion decreased after P15 for A group, P10 for B group and P8 for C and D groups. The levels of SCF, FLT3-L, IL-6 and SDF-1 in group B were higher than other groups. Karyotype analysis showed that MSCs from 4 groups were normal, and tumor-like tissues were not developed after cultured MSCs were inoculated in NOD/SCID mice. It is concluded that there was relationship between age and the biological characteristics of human bone marrow mesenchymal stem cells. For clinical use, especially in hematopoietic stem cell transplantation (HSCT), 0-20 years old donors were perfect MSCs donors who can provide sufficient MSCs in relatively short times. MSCs of group B can be used as stem cell source because the biological characteristics of MSCs of groups B are superior to that of other groups.
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PMID:[Age-related biological characteristics of human bone marrow mesenchymal stem cells from different age donors]. 1640 78

Tissue stem cells may serve as progenitors for malignant tumors derived from the same tissue. Here, we report the establishment of immortalized human mesenchymal stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous cells. Immortalization was achieved by introducing the genes for human telomerase reverse transcriptase and Bmi1. ihMSC retained the potential for multi-directional differentiation of the original MSC. To transform ihMSC, we introduced an oncogenic H-ras(Val12) gene, and established the cell line ihMSC-ras. ihMSC-ras had the phenotype of fully transformed cells and retained adipogenic and chondrogenic, but not osteogenic, potential. Interestingly, ihMSC-ras demonstrated morphological features of autophagy, and inhibition of the ERK pathway suppressed the production of autophagosomes, indicating that ras/ERK signaling is responsible for the induction of autophagy. Thus ihMSC will serve as a material with which to analyze the tumorigenic and differentiation-modifying effects of candidate oncogenes involved in the development of sarcomas.
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PMID:In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12. 1717 60

People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies.
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PMID:Repair and regeneration of osteochondral defects in the articular joints. 1793 65

The addition of antibiotics to intravaginal sponges used to synchronize ewe estrus is currently a recommended practice for the prevention of posttreatment vaginal infections. Application of this antibiotic treatment is usually done without withdrawal periods for milk, but official pharmaceutical instructions do not consider the extra-label use of antibiotics, which could result in the presence of antibiotic residues in milk. To understand the effects of the use of antibiotics on the performance of these hormonal treatments, milk collected from a group of Manchega ewes estrus synchronized by intravaginally inserted progestagen sponges jointly impregnated with antibiotics (benzyl penicillin procaine: 1,000,000 IU/25 sponges plus DH-streptomycin: 1 g/25 sponges) was evaluated for antibiotic residue persistence with 5 types of antibiotic screening tests (BRT, Copan CMT, Delvotest MSC, Eclipse 100, and New SNAP Beta-Lactams). Time to antibiotic residue depletion was established by a logistic regression model, and a significant response to milking order was observed in all methods. Positive or doubtful tests were observed after the insertion of intravaginal sponges for all assay screening tests at the time of the first milking and sometimes afterwards.
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PMID:Short communication: antibiotic residues in milk following the use of intravaginal sponges for estrus synchronization in dairy ewes. 1883 14

Pyrolytic carbon mechanical heart valves (MHVs) are widely used to replace dysfunctional and failed heart valves. As the human heart beats around 40 million times per year, fatigue is the prime mechanism of mechanical failure. In this study, a finite element approach is implemented to develop a model for fatigue analysis of MHVs due to the impact force between the leaflet and the stent and cavitation in the aortic position. A two-step method to predict crack propagation in the leaflets of MHVs has been developed. Stress intensity factors (SIFs) are computed at a small initiated crack located on the leaflet edge (the worst case) using the boundary element method (BEM). Static analysis of the crack is performed to analyse the stress distribution around the front crack zone when the crack is opened; this is followed by a dynamic crack analysis to consider crack propagation using the finite element approach. Two factors are taken into account in the calculation of the SIFs: first, the effect of microjet formation due to cavitation in the vicinity of leaflets, resulting in water hammer pressure; second, the effect of the impact force between the leaflet and the stent of the MHVs, both in the closing phase. The critical initial crack length, the SIFs, the water hammer pressure, and the maximum jet velocity due to cavitation have been calculated. With an initial crack length of 35 microm, the fatigue life of the heart valve is greater than 60 years (i.e. about 2.2 x 10(9) cycles) and, with an initial crack length of 170 microm, the fatigue life of the heart valve would be around 2.5 years (i.e. about 9.1 x 10(7) cycles). For an initial crack length greater than 170 microm, there is catastrophic failure and fatigue cracking no longer occurs. A finite element model of fatigue analysis using Patran command language (PCL custom code) in MSC software can be used to evaluate the useful lifespan of MHVs. Similar methodologies can be extended to other medical devices under cyclic loads.
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PMID:A finite element model on effects of impact load and cavitation on fatigue crack propagation in mechanical bileaflet aortic heart valve. 1902 59

In the mammalian testis, junctional adhesion molecule-B (JAM-B) is found at the blood-testis barrier between Sertoli cells and the apical ectoplasmic specializations between Sertoli and germ cells. The expression of JAM-B is tightly regulated to allow the transit of developing germ cells across the blood-testis barrier and the timely release of mature spermatids at stage VIII. In this study, the basal transcription of JAM-B in the mouse Sertoli cell line, MSC-1 cells, was examined. We found that the constitutive expression of JAM-B is carried out by the binding of specificity proteins (Sps), ETS domain transcription factor Elk-1 (Elk1), neuron-restrictive silencer factor (NRSF), and E2F transcription factor 3 (E2F3) to various cis-acting elements including TG interacting factor (TGIF), Elk-1, NRSF, and proximal Sp1 (pSp1) + E2F binding motifs. We also investigated the effects of two cytokines IL-1alpha and TGF-beta2 on JAM-B expression. IL-1alpha promotes JAM-B expression by facilitating the binding of Elk-1 to TGIF and pSp1 + E2F motifs in a p38-dependent manner, which leads to an additive effect on Sp1- and NRSF-mediated JAM-B transactivation. TGF-beta2 inhibits JAM-B transcription via the activation of mothers against decapentaplegic (Smad) proteins and activated Smads compete with specificity proteins (Sp1 and Sp3) for the TGIF motif, resulting in JAM-B repression. IL-1alpha and Smad3 expression have been reported to be stage specific. IL-1alpha is absent in the seminferous epithelium at stages VII-VIII, whereas a high level of nuclear Smad3 level is found at the same stages. This study shows for the first time that IL-1alpha and TGF-beta2 regulate JAM-B expression in an opposite manner, and in vitro data obtained herein provide some clues on how junctions are regulated in the testis.
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PMID:Opposite effects of interleukin-1alpha and transforming growth factor-beta2 induce stage-specific regulation of junctional adhesion molecule-B gene in Sertoli cells. 1916 72

Bone marrow derived mesenchymal stem cells (BM-MSC) can differentiate into chondrocytes. Understanding the mechanisms and growth factors that control the MSC stemness is critical to fully implement their therapeutic use in cartilage diseases. The activated type 1 insulin-like growth factor receptor (IGF-IR), interacting with the insulin receptor substrate-1 (IRS-1), can induce cancer cell proliferation and transformation. In cancer or transformed cells, IRS-1 has been shown to localize in the cytoplasm where it activates the canonical Akt pathway, as well as in the nucleus where it binds to nuclear proteins. We have previously demonstrated that IGF-I has distinct time-dependent effect on primary BM-MSC chondrogenic pellets: initially (2-day culture), IGF-I induces proliferation; subsequently, IGF-I promotes chondrocytic differentiation (7-day culture). In the present study, by using MSC from the BM of IRS-1(- / - ) mice we show that IRS-1 mediates almost 50% of the IGF-I mitogenic response and the MAPK-MEK/ERK signalling accounts for the other 50%. After stimulation with IGF-I, we found that in 2-day old human and mouse derived BM-MSC pellets, IRS-1 (total and phosphorylated) is nuclearly localized and that proliferation prevails over differentiation. The IGF-I mitogenic effect is Akt-independent. In 7-day MSC pellets, IGF-I stimulates the chondrogenic differentiation of MSC into chondrocytes, pre-hypertrophic and hypertrophic chondrocytes and IRS-1 accumulates in the cytoplasm. IGF-I-dependent differentiation is exclusively Akt-dependent. Our data indicate that in the physiologically relevant model of primary cultured MSC, IGF-I induces a temporally regulated nuclear or cytoplasmic localization of IRS-1 that correlate with the transition from proliferation to chondrogenic differentiation.
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PMID:Subcellular localization of IRS-1 in IGF-I-mediated chondrogenic proliferation, differentiation and hypertrophy of bone marrow mesenchymal stem cells. 1963 89

Pancreatic islet beta-cell replenishment can be driven by epithelial cells from exocrine pancreas via epithelial-mesenchymal transition (EMT) and the reverse process MET, while specified pancreatic mesenchymal cells control islet cell development and maintenance. The role of human islet-derived precursor cells (hIPCs) in regeneration and support of endocrine islets is under investigation. Here, we analyzed hIPCs as to their immunophenotype, multilineage differentiation capacity, and gene profiling, in comparison to human bone marrow-derived mesenchymal stem cells (hBM-MSCs). hIPCs and hBM-MSCs display a common mesenchymal character and express lineage-specific marker genes upon induction toward pancreatic endocrine and mesenchymal pathways of differentiation. hIPCs can go further along endocrine pathways while lacking some core mesenchymal differentiation attributes. Significance analysis of microarray (SAM) from 5 hBM-MSC and 3 hIPC donors mirrored such differences. Candidate gene cluster analysis disclosed differential expression of key lineage regulators, indicated a HoxA gene-associated positional memory in hIPCs and hBM-MSCs, and showed as well a clear transition state from mesenchyme to epithelium or vice versa in hIPCs. Our findings raise new research platforms to further clarify the potential of hIPCs to undergo complete MET thus contributing to islet cell replenishment, maintenance, and function.
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PMID:Functional signature of human islet-derived precursor cells compared to bone marrow-derived mesenchymal stem cells. 1989 35

Using human MSCs (mesenchymal stem cells) lacking VEGF (vascular endothelial growth factor) receptors, we show that the pro-angiogenic receptor neuropilin-1 associates with phosphorylated PDGFRs [PDGF (platelet-derived growth factor) receptors], thereby regulating cell signalling, migration, proliferation and network assembly. Neuropilin-1 co-immunoprecipitated and co-localized with phosphorylated PDGFRs in the presence of growth factors. Neuropilin-1 knockdown blocked PDGF-AA-induced PDGFRalpha phosphorylation and migration, reduced PDGF-BB-induced PDGFRbeta activation and migration, blocked VEGF-A activation of both PDGFRs, and attenuated proliferation. Neuropilin-1 prominently co-localized with both PDGFRs within MSC networks assembled in Matrigel and in the chorioallantoic membrane vasculature microenvironment, and its knockdown grossly disrupted network assembly and decreased PDGFR signalling. Thus neuropilin-1 regulates MSCs by forming ligand-specific receptor complexes that direct PDGFR signalling, especially the PDGFRalpha homodimer. This receptor cross-talk may control the mobilization of MSCs in neovascularization and tissue remodelling.
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PMID:Neuropilin-1 regulates platelet-derived growth factor receptor signalling in mesenchymal stem cells. 2010 35

The current study was undertaken with the goal being isolation, cultivation, and characterization of ovine mesenchymal stem cells (oMSC). Furthermore, the objective was to determine whether biological active polycaprolactone-co-lactide (trade name PCL) scaffolds support the growth and differentiation of oMSC in vitro. The oMSC were isolated from the iliac crest of six merino sheep. Three factors were used to demonstrate the MSC properties of the isolated cells in detail. (1) Their ability to proliferate in culture with a spindle-shaped morphology, (2) presence of specific surface marker proteins, and (3) their capacity to differentiate into the three classical mesenchymal pathways, osteoblastic, adipogenic, and chondrogenic lineages. Furthermore, embroidered PCL scaffolds were coated with collagen I (coll I) and chondroitin sulfate (CS). The porous structure of the scaffolds and the coating with coll I/CS allowed the oMSC to adhere, proliferate, and to migrate into the scaffolds. The coll I/CS coating on the PCL scaffolds induced osteogenic differentiation of hMSC, without differentiation supplements, indicating that the scaffold also has an osteoinductive character. In conclusion, the isolated cells from the ovine bone marrow have similar morphologic, immunophenotypic, and functional characteristics as their human counterparts. These cells were also found to differentiate into multiple mesenchymal cell types. This study demonstrates that embroidered PCL scaffolds can act as a temporary matrix for cell migration, proliferation, and differentiation of oMSC. The data presented will provide a reliable model system to assess the translation of MSC-based therapy into a variety of valuable ovine experimental models under autologous settings.
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PMID:Ovine bone marrow mesenchymal stem cells: isolation and characterization of the cells and their osteogenic differentiation potential on embroidered and surface-modified polycaprolactone-co-lactide scaffolds. 2049 Jul 6


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