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2.  Comparison of Bioabsorbable Suture Anchor Fixation on the Tibial Side for Anterior Cruciate Ligament Reconstruction Using Free Soft Tissue Graft: Experimental Laboratory Study on Porcine Bone 
Yonsei Medical Journal  2014;55(3):760-765.
Purpose
The use of graft tissue fixation using bioabsorbable interference screws (BISs) in anterior cruciate ligament (ACL) reconstruction offers various advantages, but limited pullout strength. Therefore, additional tibial fixation is essential for aggressive rehabilitation. We hypothesized that additional graft tissue fixation using bioabsorbable suture anchors (BSA) would provide sufficient pull-out strength.
Materials and Methods
Twenty four fresh frozen porcine distal femur and patellar tendon preparations were used. All specimens were divided into three groups based on additional fixation methods: A, isolated BIS; B, BIS and BSA; and C, BIS and post cortical screw. Tensile testing was carried out under an axial load. Ultimate failure load and ultimate failure load after cyclic loading were recorded.
Results
The ultimate failure loads after load to failure testing were 166.8 N in group A, 536.4 N in group B, and 438 N in group C; meanwhile, the ultimate failure loads after load to failure testing with cyclic loading were 140 N in group A, 466.5 N in group B, and 400 N in group C. Stiffness after load to failure testing was 16.5 N/mm in group A, 33.5 N/mm in group B, and 40 N/mm in group C. An additional BSA fixation resulted in a significantly higher ultimate failure load and stiffness than isolated BIS fixation, similar to post screw fixation.
Conclusion
Additional fixation using a BSA provided sufficient pullout strength for ACL reconstruction. The ultimate failure load of the BSA technique was similar to that of post cortical screws.
doi:10.3349/ymj.2014.55.3.760
PMCID: PMC3990092  PMID: 24719145
Anterior cruciate ligament reconstruction; graft; tissue fixation; suture anchor
3.  Exercise Training Improves Cardiac Autonomic Nervous System Activity in Type 1 Diabetic Children 
[Purpose] We investigated the effect exercise training has on cardiac autonomic nervous system (ANS) and cardiovascular risk profiles in children with type 1 diabetes mellitus (DM). [Subjects] Fifteen type 1 DM children (all boys; 13.0±1.0 years of age) were enrolled in the study. [Methods] The subjects received exercise training three times a week in a 12-week program. Each child was asked to walk on a treadmill to achieve an exercise intensity of VO2max 60%. ANS activity was measured by power spectral analysis of the electrocardiogram (ECG). Blood samples were obtained for serum lipid profiles. To evaluate Doppler-shifted Fourier pulsatility index (PI) analysis, a 5-MHz continuous wave Doppler (VASCULAB D10) set was used to measure forward blood flow velocity (FLOW) in the radial artery. [Results] Total and low-frequency (LF) power of heart rate variability increased significantly after exercise intervention. Total cholesterol (TC) levels were significant lower after exercise intervention. Total and high-frequency (HF) power were significantly correlated with higher TC levels, but diastolic blood pressure and HF was significantly correlated with lower TC levels. [Conclusion] Regular exercise intervention should be prescribed for children with type 1 DM.
doi:10.1589/jpts.26.111
PMCID: PMC3927020  PMID: 24567687
Autonomic nervous system; Exercise; Diabetes mellitus
4.  Charge-transfer interaction mediated organogels from 18β-glycyrrhetinic acid appended pyrene 
Summary
We describe herein the two-component charge-transfer (CT) interaction induced organogel formation with 18β-glycyrrhetinic acid appended pyrene (GA-pyrene, 3) as the donor, and 2,4,7-trinitrofluorenone (TNF, 4) as the acceptor. The use of TNF (4) as a versatile electron acceptor in the formation of CT gels is demonstrated through the formation of gels in a variety of solvents. Thermal stability, stoichiometry, scanning electron microscopy (SEM), optical micrographs, and circular dichroism (CD) are performed on these CT gels to investigate their thermal and assembly properties. UV–vis, fluorescence, mass spectrometric as well as variable-temperature 1H NMR experiments on these gels suggest that the CT interaction is one of the major driving forces for the formation of these organogels.
doi:10.3762/bjoc.9.324
PMCID: PMC3869347  PMID: 24367453
charge transfer; glycyrrhetinic acid; organogel; self-assembly
5.  Proteomic analysis identifies proteins associated with curcumin-enhancing efficacy of irinotecan-induced apoptosis of colorectal cancer LOVO cell 
Objective: We wish to implement a proteomics-based approach to pick and identify the proteins associated with curcumin enhancing efficacy of irinotecan inducing apoptosis of colorectal cancer LOVO cells, and further explore their synergy mechanism by bioinformatics. Methods: A colorectal cancer cell line (LOVO cell) treated by curcumin combined with irinotecan in different ways respectively was used as our comparative model. Protein spots were analyzed through MALDI-TOF/TOF. The location and function of differential protein spots were analyzed through UniProt database. Protein-protein interactions were examined through String software. Results: A total of 54 protein spots differentially expressed with 1.5-fold difference were picked, 11 of which were repeated. They mainly were involved in intracellular calcium pathways, cellular respiratory chain pathway and intracellular redox reaction pathways of LOVO cell. According to the function of various protein points, combining with varying curves of protein points in each treatment groups, we selected five interesting protein spots, 4 of which exists Protein-protein interactions, and they were close to the formation and reduction of disulfides in intracellular endoplasmic reticulum (ER). Conclusion: We selected preliminary but comprehensive data about differential expression protein spots of LOVO cell. Among these, the five interesting differential expression protein spots identified in this study may provide new insight into LOVO cell therapeutic biomarkers. Curcumin may suppress GSTM5 expression to enhance the lethal effect of irinotecan on LOVO cells, and maybe their combination via the affection of PDI and PRDX4 to disturb the formation and reduction of disulfides results in inducing apoptosis of LOVO cell.
PMCID: PMC3885455  PMID: 24427321
Curcumin; irinotecan; proteomics; colorectal cancer
6.  Copper-Catalyzed Ortho-Acylation of Phenols with Aryl Aldehydes and Its Application in One-Step Preparation of Xanthones 
In the presence of triphenylphosphine, copper (II) chloride can catalyze an intermolecular ortho-acylation reaction of phenols with aryl aldehydes. The reaction proceeds smoothly with a wide range of starting materials, and furthermore, it can be used to synthesize xanthone derivatives in a single step with high-yields.
doi:10.1039/c2cc36176k
PMCID: PMC3496182  PMID: 23069775
7.  Tau in MAPK Activation 
The nature of “toxic” tau in Alzheimer’s disease (AD) has been unclear. During pathogenesis, the importance of tau oligomerization vs. tau phosphorylation is controversial and the investigation of both remains critical toward defining the “toxicity” of tau. The phosphorylation of tau on serines and/or threonines occurs early in the disease course and altering phosphorylation has been shown to disrupt neuropathogenesis. We have recently reported that in PC12-derived cells, tau had a role in signal transduction processes activated by NGF. By depleting tau, NGF-induced MAPK activation was attenuated and by restoring tau, MAPK activation was restored. Furthermore, the phosphorylation of tau on Thr231 was required for tau to potentiate MAPK activation. Here we report the effects of additional disease-related tau phosphorylation sites and tau isoform on the ability of tau to potentiate MAPK activation. Our findings, which tested three other sites of phosphorylation, showed that phosphorylation at these other sites mainly lessened MAPK activation; none potentiated MAPK activation. In comparing 0N3R tau to the other five brain tau isoforms, most showed a trend toward less MAPK activation, with only 2N4R tau showing significantly less activation. Since MAPK activation has been reported in AD brain and is characteristic of cell proliferation mechanisms, tau phosphorylation that promotes MAPK activation could promote cell cycle activation mechanisms. In neurons, the activation of the cell cycle leads to cell death, suggesting that abnormally phosphorylated tau can be a toxic species. The relationship between tau oligomerization and its ability to potentiate MAPK activation needs to be determined.
doi:10.3389/fneur.2013.00161
PMCID: PMC3797993  PMID: 24146661
tau; MAPK activation; phosphorylation; signal transduction; NGF
8.  Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells 
Cytotechnology  2012;64(4):421-428.
Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.
doi:10.1007/s10616-011-9419-9
PMCID: PMC3397113  PMID: 22274625
AEGA; Glycyrrhetinic acid derivative; Apoptosis; Mitochondrial membrane potential; Bcl-2/Bax; Human leukemic cells
9.  Hip structural analysis: a comparison of DXA with CT in postmenopausal Japanese women 
SpringerPlus  2013;2:331.
Geometry of the proximal femur is one determinant of fracture risk, and can be analyzed by a simple method using dual-energy X-ray absorptiometry (DXA). The aim of the present study was to investigate the accuracy of hip structural analysis (HSA) using clinical data in postmenopausal Japanese women. A total of 184 postmenopausal women aged 51–88 years (mean, 70.5 ± 8.7 years) who underwent artificial joint replacement surgery for osteoarthrosis of the hip or knee joint were included. Computed tomography (CT) data from preoperative assessment were utilized for analysis of proximal femoral geometry (CT-HSA) using QCTPro Software (Mindways Software Inc., Austin, TX) and compared with HSA results based on DXA (DXA-HSA). The results of femoral geometry were further compared with a CT-based finite-element method (CT/FEM). There was moderate to high correlation between DXA-HSA and CT-HSA (r=0.60-0.90, p<0.001), except for the buckling ratio in the intertrochanteric region. Moreover, the correlation of HSA with CT/FEM was similar between DXA-HSA and CT-HSA. The present results suggest that the geometry of proximal femoral cross sections can be reasonably well characterized using DXA.
doi:10.1186/2193-1801-2-331
PMCID: PMC3724983  PMID: 23961402
Hip structural analysis; CT-based finite-element method; Bone strength; QCT
10.  Jump exercise during hindlimb unloading protect against the deterioration of trabecular bone microarchitecture in growing young rats 
SpringerPlus  2013;2:35.
Three-dimensional femoral trabecular architecture was investigated in tail-suspended young growing rats and the effects of jump exercise during the period of tail-suspension were also examined. Eight-week-old male Wistar rats (n = 24) were randomly assigned to three body weight-matched groups: a tail suspended group (SUS, n = 8); a sedentary control group (CON, n = 8) and rats primed with jump exercise during the period of tail suspension (JUM, n = 8). The jump exercise protocol consisted of 30 jumps/day, five days/week with a 40 cm jump height. After 3 weeks of jump exercise, bone mineral density (BMD) of the entire right femur was measured using dual energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography (micro-CT). Tail suspension caused a decrease in femoral BMD (−5%, p < 0.001) and trabecular bone architectural deterioration. Deterioration in the trabecular network during hindlimb unloading was mostly attributed to the reduction of trabecular number (−32%, p < 0.001) in the distal femoral metaphysis. Jump exercise during the tail suspension period increased trabecular thickness (14%, p < 0.001) and the reduction of trabecular number was suppressed. The present data indicate that jump exercise applied during hindlimb unloading could be able to inhibit bone loss and trabecular bone architectural deterioration caused by tail suspension.
doi:10.1186/2193-1801-2-35
PMCID: PMC3597269  PMID: 23503945
Jump exercise; Tail suspension; Trabecular bone; Microarchitecture; Microcomputed tomography
11.  Therapeutic effect of transplanting magnetically labeled bone marrow stromal stem cells in a liver injury rat model with 70%-hepatectomy 
Summary
Background
There are only few reports about the use of bone marrow stromal stem cells (BMSCs) for the treatment of traumatic liver injury. This study aimed to study the therapeutic effect of fluorescence-labeled BMSCs administered to rats subject to traumatic liver injury.
Material/Methods
Male SD rats with a 70% resection of the liver were injected with feridex-labeled BMSCs which could be induced to functional hepatocytes in vitro. Liver function was assayed and the liver scanned by 1.5-T MRI at 12 hrs and on days 1, 3, 5, 7, and 14 post-operation. The pathological changes of liver sections were monitored.
Results
The serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin in the transplantation group were significantly lower than the control group. The MRI showed rats of the transplantation group had an oval low signal area at 12 hr after operation; the low signal range gradually expanded and the signal intensity gradually decreased over 14 days after operation. The low signal range in the control group disappeared 12 hr after the operation. After Prussian blue staining, rats of the transplantation group contained blue granules with no significant hypertrophy or edema in hepatocytes, while the control group showed no blue granules with significant hypertrophy and edema.
Conclusions
The BMSCs transplanted into the injured rat liver gradually migrate to the surrounding liver tissue and partially repair the liver surgical injury in rats. BMSCs may represent an effective therapeutic approach for acute liver injury.
doi:10.12659/MSM.883476
PMCID: PMC3560556  PMID: 23018343
bone marrow stromal stem cells; traumatic liver injury; cell transplantation; MRI; rat
12.  Surgical Management of Aortic Root Dilatation with Advanced Aortic Regurgitation: Bentall Operation versus Valve-sparing Procedure 
Background
Although the aortic valve-sparing procedure has gained popularity in recent years, it still remains challenging in patients with advanced aortic regurgitation (AR). We compared the long-term outcomes of the aortic valve-sparing procedure with the Bentall operation in patients with advanced aortic regurgitation secondary to aortic root dilatation.
Materials and Methods
A retrospective review of 120 patients who underwent surgery for aortic root dilatation with moderate to severe AR between January 1999 and June 2009 was performed. Forty-eight patients underwent valve-sparing procedures (valve-sparing group), and 72 patients underwent the Bentall procedure (Bentall group). The two groups' overall survival, valve-related complications, and aortic valve function were compared.
Results
The mean follow-up duration was 4.9±3.1 years. After adjustment, the valve-sparing group had similar risks of death (hazard ratio [HR], 0.61; p=0.45), and valve related complications (HR, 1.27; p=0.66). However, a significant number of patients developed moderate to severe AR in the valve-sparing group at a mean of 4.4±2.5 years of echocardiographic follow-up (p<0.001).
Conclusion
Both the Bentall operation and aortic valve-sparing procedure showed comparable long-term clinical results in patients with advanced aortic regurgitation with aortic root dilatation. However, recurrent advanced aortic regurgitation was more frequently observed following valve-sparing procedures.
doi:10.5090/kjtcs.2012.45.3.141
PMCID: PMC3373968  PMID: 22708080
Aortic root; Aortic valve insufficiency; Bentall operation; Aortic valve repair
13.  Cardiac Angiosarcoma on the Right Atrium: Two Cases 
We detected two cases of right atrial angiosarcoma that had a similar appearance on imaging studies. Although the surgical findings were similar for the two patients, one had a clear resection margin, while the other had tumor cells in the resection margin on frozen biopsy. We suggest that preoperative data on magnetic resonance imaging and computed tomography in patients with angiosarcomas may not predict the exact extent of surgical resection or prognostic outcomes.
doi:10.5090/kjtcs.2012.45.2.120
PMCID: PMC3322182  PMID: 22500283
Heart neoplasms; Malignant tumor; Hemangiosarcoma
14.  Axillofemoral Bypass to Treat Severe Heart Failure Caused by Takayasu's Arteritis 
Takayasu's arteritis is an inflammatory vasculitis that primarily affects the aorta and its major branches. Involvement of the thoracic and abdominal aortas, although rare, causes marked hypertension and may lead to severe heart failure. We report the improvement of cardiac function after axillofemoral bypass grafting in a 59-year-old woman who had this condition.
doi:10.5090/kjtcs.2012.45.2.124
PMCID: PMC3322183  PMID: 22500284
Takayasu's arteritis; Arterial bypass
15.  A 69-year-old Woman with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery: Surgical Repair Using a Trap-door Flap 
We present a patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), which was diagnosed and corrected in her 60 s. The patient is the oldest documented survivor of ALCAPA who underwent a surgical repair. ALCAPA should be corrected surgically to restore the dual coronary system at any age and this case shows that the surgical procedure may be performed safely even in an elderly patient.
doi:10.5090/kjtcs.2011.44.5.358
PMCID: PMC3249340  PMID: 22263188
Coronary artery pathology; ALCAPA syndrome
16.  Clinical, Pharmacokinetic, and Pharmacogenetic Determinants of Clopidogrel Resistance in Korean Patients with Acute Coronary Syndrome 
Background
Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS.
Methods
Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed.
Results
A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value<0.0001).
Conclusions
The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.
doi:10.3343/kjlm.2011.31.2.91
PMCID: PMC3116006  PMID: 21474982
Acute coronary syndrome; Clopidogrel resistance; CYP2C19; Korean; Platelet inhibition
17.  Deuterium-depleted water inhibits human lung carcinoma cell growth by apoptosis 
To investigate the in vivo and in vitro inhibitory effects of deuterium-depleted water (DDW) on human lung cancer and the possible mechanisms underlying these effects, we cultured and treated human lung carcinoma cell line A549 and human embryonic lung fibroblasts HLF-1 with various concentrations of DDW from 2 to 72 h. Cellular growth inhibition rates were determined using the 3-(4, 5-dimethyldiazol-2-yl)-2, 5-diphenyltetrazolium-bromide) (MTT) proliferation assay. A549 cells were treated with 50±5 ppm DDW, and the morphology and structure of cells were observed by scanning electron microscopy (SEM). We observed alterations in the cellular skeleton by transmission electron microscopy (TEM) and changes in cell cycle by flow cytometry. Our data showed that DDW significantly inhibited the proliferation of A549 cells at a specific time point, and cells demonstrated the characteristic morphological changes of apoptosis under SEM and TEM. The length of the S phase increased significantly in cells treated with 50 ppm DDW, whereas the G0 to G1 phase and G2 to M phase were decreased. We observed DDW-induced cellular apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and DNA fragment analyses. In addition, we established a tumor transplantion model by injecting H460 tumor cells into subcutaneous tissue of BALB/c mice treated with DDW for 60 days. We determined the tumor inhibition rate of treated and control groups and found that the tumor weight was significantly decreased and the tumor inhibition rate was approximately 30% in the DDW group. We conclude that DDW is a promising new anticancer agent with potential for future clinical application.
doi:10.3892/etm_00000043
PMCID: PMC3445928  PMID: 22993540
deuterium-depleted water; lung cancer; inhibition; apoptosis
18.  Hybrid Procedure for a Traumatic Aortic Rupture Consisting of Endovascular Repair and Minimally Invasive Arch Vessel Transposition without Sternotomy 
Journal of Korean Medical Science  2009;25(1):142-144.
Emergency surgical repair for acute traumatic aortic ruptures has been associated with a high peri-procedural mortality rate. Endovascular stent-grafting, as a less invasive procedure, has shown encouraging results. This report describes a patient with a short landing zone, who was treated by transposing the supra-aortic branch without sternotomy, followed by covered stent-grafting with an extended proximal bare portion to enhance fixation.
doi:10.3346/jkms.2010.25.1.142
PMCID: PMC2800019  PMID: 20052360
Aorta; Wounds and Injuries; Stent-graft
19.  Spectroscopic Interpretation of PAH-Spectra in Minerals and Its Possible Application to Soil Monitoring 
Sensors (Basel, Switzerland)  2010;10(4):3868-3881.
In order to properly assess the feasibility of using Laser-Induced Fluorescence (LIF) spectroscopy for soil monitoring, the variation of fluorescence intensity due to the heterogeneity and complexity of soil media was investigated. Different soil minerals showed fluorescence spectral structures distinguishable from the contaminants, implying dissimilar interactions or the binding of contaminants on mineral surfaces. More interestingly, solvent and water addition showed different responses in the fluorescence spectral structure showing their effect on the interactions between contaminants and minerals. These results support the claim that the spectral structure contains information on contaminant-mineral interactions; therefore contaminants can be used as a fluorescence probe for these interactions.
doi:10.3390/s100403868
PMCID: PMC3274252  PMID: 22319331
PAH; fluorescence; spectral structure; contaminant-soil interaction
20.  Benzyl 3-dehydr­oxy-1,2,5-oxadiazolo[3′,4′:2,3]oleanolate 
The title compound, C37H50N2O3, is a benzyl ester derivative of oleanolic acid, a penta­cyclic triterpene, with a five-membered oxadiazole ring fused to the ring A. The triterpene A and C rings adopt slightly distorted half-chair conformations, whereas the remaining three six-membered rings are in chair forms.
doi:10.1107/S1600536809026695
PMCID: PMC2977140  PMID: 21583566
21.  1,2,5-Oxadiazolo[3,4-b]glycyrrhetinic acid 
The title compound [systematic name: 11-oxo-2,3-(oxy­dinitrilo)olean-12-en-29-oic acid], C30H42N2O4, contains a linear array of five six-membered rings and a five-membered heterocyclic ring. The C ring, containing an α,β-unsaturated ketone, has a slightly distorted half-chair conformation, as does the A ring, with N—C—C angles 125.3 (5), 111.2 (4), 124.9 (5) and 109.2 (5)°, while the other three six-membered rings adopt chair conformations. The enanti­omer has been assigned by reference to unchanging chiral centres in the synthetic procedure. An intramolecular C—H⋯O interaction is present. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules.
doi:10.1107/S1600536809020996
PMCID: PMC2969501  PMID: 21582833
22.  CT-Guided Percutaneous Vertebroplasty in the Treatment of an Upper Thoracic Compression Fracture 
Korean Journal of Radiology  2009;10(2):185-189.
Percutaneous vertebroplasty (PVP) has been used to relieve pain and to prevent further collapse of the vertebral body in patients with an osteoporotic compression fracture. The most commonly affected site for the use of PVP is the thoracolumbar junction. There are few reports that have described on the usefulness of PVP in the treatment of a high thoracic compression fracture. We report a case of an upper thoracic compression fracture that was treated with computed tomography (CT)-guided PVP. It was possible to obtain easy access to the narrow thoracic pedicle and it was also possible to monitor continuously the proper volume of polymethylmethacrylate employed, under CT guidance.
doi:10.3348/kjr.2009.10.2.185
PMCID: PMC2651434  PMID: 19270865
Compression fracture; Computed tomography (CT)-guided PVP; High thoracic; Polymethylmethacrylate
23.  Bone morphogenetic protein 4 stimulates neuronal differentiation of neuronal stem cells through the ERK pathway 
Experimental & Molecular Medicine  2009;41(2):116-125.
Bone morphogenic protein 4 (BMP4), a member of the TGF-β superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker β-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/β-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3β (GSK3β) activating the Wnt/β-catenin pathway. The BMP4-mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.
doi:10.3858/emm.2009.41.2.014
PMCID: PMC2679327  PMID: 19287192
bone morphogenetic protein 4; cell differentiation; extracellular signal-regulated MAP kinases; neurons; stem cells; valproic acid
24.  Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the beta-catenin-Ras-ERK-p21Cip/WAF1 pathway 
BMC Cell Biology  2008;9:66.
Background
Valproic acid (VPA), a commonly used mood stabilizer that promotes neuronal differentiation, regulates multiple signaling pathways involving extracellular signal-regulated kinase (ERK) and glycogen synthase kinase3β (GSK3β). However, the mechanism by which VPA promotes differentiation is not understood.
Results
We report here that 1 mM VPA simultaneously induces differentiation and reduces proliferation of basic fibroblast growth factor (bFGF)-treated embryonic day 14 (E14) rat cerebral cortex neural progenitor cells (NPCs). The effects of VPA on the regulation of differentiation and inhibition of proliferation occur via the ERK-p21Cip/WAF1 pathway. These effects, however, are not mediated by the pathway involving the epidermal growth factor receptor (EGFR) but via the pathway which stabilizes Ras through β-catenin signaling. Stimulation of differentiation and inhibition of proliferation in NPCs by VPA occur independently and the β-catenin-Ras-ERK-p21Cip/WAF1 pathway is involved in both processes. The independent regulation of differentiation and proliferation in NPCs by VPA was also demonstrated in vivo in the cerebral cortex of developing rat embryos.
Conclusion
We propose that this mechanism of VPA action may contribute to an explanation of its anti-tumor and neuroprotective effects, as well as elucidate its role in the independent regulation of differentiation and inhibition of proliferation in the cerebral cortex of developing rat embryos.
doi:10.1186/1471-2121-9-66
PMCID: PMC2639384  PMID: 19068119

Results 1-24 (24)