[show abstract][hide abstract] ABSTRACT: Formaldehyde (FA) is toxic to the respiratory system, and nitric oxide (NO) dysfunction stimulates the onset of respiratory diseases. The involvement of dimethylarginine dimethylaminohydrolase (DDAH), the L-arginine analogue asymmetric dimethylarginine (ADMA) degrading enzyme, in FA-induced cell death in lung epithelial cells has not been investigated. In this study, we assessed the effect of FA on DDAH expression and endoplasmic reticulum (ER) stress in A549 cells. We also investigated the preventive effect of DDAH overexpression on ER stress and apoptosis in FA-induced cell death. FA decreased viability in A549 cells and decreased DDAH1 and DDAH2 mRNA and protein expression in a time-dependent manner (>4h). This coincided with increased phosphorylation of the ER stress proteins IRE1α, PERK, and eIF-2α, as well as increased expression of pro-apoptotic proteins such as Bax, C/EPB homologous protein (CHOP), cleaved PARP, and cleaved caspase-3, but decreased expression of the anti-apoptotic protein Bcl-2. ADMA treatment mimicked the effect of FA. Overexpression of DDAH1, but not DDAH2, prevented FA-induced decreases in cell viability, phosphorylation of IRE1α, PERK, and eIF2α, and expression of CHOP. Effects of DDAH1 overexpression, but not DDAH2 overexpression, restored FA-induced increases in Bax, CHOP, cleaved PARP, cleaved caspase-3 and decreases in Bcl-2. In conclusion, FA induces apoptosis of lung epithelial cells via a decrease of DDAH 1 through ER stress.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 10/2013; · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: Purpose: Stromal cell-derived factor 1 (SDF-1) and its interaction with chemokine receptor 4 (CXCR4) have been noted for participating in wound healing process, and may paradoxically develop hypertrophic scarring. With viewing pterygia as products of exaggerated wound formation, we evaluated the effects of SDF-1 and CXCR4 on determining the severity of pterygia. Methods: Human pterygial fibroblasts were cultured from excised tissues. Then, expression levels of SDF-1 and CXCR4 were assessed at both the mRNA and protein levels and analyzed with respect to the severity (grade T1 to T3) of pterygia. Expression patterns of SDF-1 and CXCR4 in pterygium tissues were evaluated by immunohistochemistry. Additionally, to investigate the SDF-1-induced myofibroblast transformation of pterygial fibroblasts, the correlation between SDF-1 and α-smooth muscle actin (α-SMA) expression levels was evaluated. Furthermore, α-SMA levels in pterygial fibroblasts were determined before and after knockdown of SDF-1 and blockade of CXCR4 by AMD3100. Results: SDF-1 and CXCR4 were expressed in identical areas in severe pterygium tissues (grade T3) and CXCR4-immunopositive cells were concentrated at perivascular regions. SDF-1 levels in cultured pterygial fibroblasts correlated positively with the severity of pterygia. SDF-1 levels had a significant positive correlation with α-SMA levels in pterygial fibroblasts. Furthermore, each knockdown of SDF-1 expression and blockade of SDF-1/CXCR4 signaling in severe pterygia significantly reduced α-SMA levels. Conclusions: SDF-1 expression is upregulated in severe pterygia. And SDF-1 and CXCR4 interaction may contribute to the myofibroblast transformation which can be possibly restored through the downregulation of the SDF-1/CXCR4 axis.
[show abstract][hide abstract] ABSTRACT: Severe hypoxic and ischemic injury leads to primary graft dysfunction after lung transplantation. Arginine methylation, which is responsible for the regulation of a variety of biological functions, is mediated by protein arginine methylation transferases (PRMTs). This study examined the role of hypoxia in PRMT activation in A549 human lung epithelial cells, as well as the role of ischemia in PRMT activation in the lung of miniature pigs. In A459 cells, hypoxia increased the expression of PRMT1 and PRMT5, and overexpression of PRMT1 and PRMT5 induced apoptosis. The transfection of PRMT1 and PRMT5 small interfering RNA (siRNA) prevented hypoxia-inducible factor (HIF)-1α expression and apoptosis in A549 cells. Hypoxia-induced expression of PRMT1 and PRMT5 was blocked by p38 and JNK mitogen-activated protein kinase (MAPK) inhibitors, but not by an inhibitor of extracellular signal-regulated kinases (ERK) 1/2. In the lungs of miniature pigs, ischemia stimulated PRMT1 and PRMT5 expression and induced phosphorylation of p38 MAPK (p-p38), phosphorylation of JNK (p-JNK), and apoptotic molecules. These results demonstrate that PRMT1 and PRMT5 are involved in hypoxia and ischemia-induced apoptosis via p-p38 MAPK and p-JNK in in vitro and in vivo models.
Biochemical and Biophysical Research Communications 10/2013; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examine the effect of rosmarinic acid (RA) in chemical hypoxia-induced injury in rat hepatocytes. Cell viability was significantly decreased by cobalt chloride (CoCl2), a well-known hypoxia mimetic agent in a time- and dose- dependent manner. RA pretreatment before exposure to CoCl2 significantly attenuated the CoCl2-induced decrease of cell viability. Additionally, pretreatment with RA potentiated the decrease of Bcl-2 expression and attenuated the increase of Caspase-3 expression by CoCl2. CoCl2 treatment resulted in an increase of intracellular ROS generation, which is inhibited by RA or N-acetyl-cysteine (NAC, a ROS scavenger), and p38MAPK phosphorylation, which is also blocked by RA or NAC. CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3 expression was attenuated by RA, NAC and SB203580 (p38MAPK inhibitor). CoCl2-induced decrease of cell viability was also attenuated by RA, NAC and SB203580 pretreatment. Additionally, RA inhibited CoCl2-induced COX-2 expression and prostaglandin E2 (PGE2) secretion. Similar to the effect of RA, both NAC and NS-398 (COX-2 inhibitor) blocked CoCl2-induced COX-2 expression and PGE2 secretion. NS-398 attenuated not only CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3 expression, but decrease of cell viability. Taken together, RA protects primary cultured rat hepatocytes against CoCl2-induced cell injury through inhibition of ROS-activated p38MAPK and COX-2/PGE2 pathway.
Archives of Pharmacal Research 10/2013; · 1.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although recent findings showed that the bioactive lipid metabolites can regulate the ES cell functions, the physiological relevance of interaction between sphingosine-1-phosphate (S1P) and Flk-1 and its related signaling molecules are not yet clear in ES cell proliferation. In the present study, S1P1-5 receptors were expressed in mouse ES cells and S1P increased S1P1-3 receptor expression level. S1P treatment stimulated the cellular proliferation in S1P1/3-dependent manner, located in lipid rafts. In response to S1P, β-arrestin was recruited to S1P1/3 receptor and c-Src was activated. S1P also increased the binding of S1P1/3 receptor with Flk-1. Similar to responses for VEGF, S1P increased Flk-1 phosphorylation, which was blocked by β-arrestin siRNA, and PP2, but not by VEGF-A164 antibody or VEGF siRNA. In addition, S1P induced VEGF expression and VEGFR2 kinase inhibitor (SU1498) blocked the S1P-induced cellular proliferation. However, VEGF-A164 antibody or VEGF siRNA partially blocked S1P-induced cellular proliferation, suggesting that both VEGF-dependent Flk-1 activation and VEGF-independent Flk-1 activation are involved in S1P-induced ES cell proliferation. S1P and VEGF-induced phosphorylation of ERK and JNK were blocked by pretreatment with SU1498. Moreover, inhibition of ERK and JNK blocked S1P-induced cellular proliferation. In conclusion, S1P-elicited transactivation of Flk-1 mediated by S1P1/3-dependent β-arrestin/c-Src pathways stimulated mouse ES cell proliferation.
Stem cell research 09/2013; 12(1):69-85. · 3.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Angiogenin (ANG) was originally identified as an angiogenic tumor factor, and recently its biological activity is extended to stimulating cell proliferation. With viewing pterygium as a tumorigenic mimicry, we investigated ANG profiles within pterygia.
Expression levels of ANG were assessed using immunohistochemistry, RT-PCR and Western blotting through examination of both excised specimens and cultured fibroblasts from pterygium and conjunctiva tissues. The phenotypes of pterygia were classified by four grading indices including recurrence, growth activity, pterygium body translucency (T) and vascularity (V). Then, ANG levels in pterygia were differentiated according to phenotypes of pterygia, and were compared to levels in normal conjunctiva. Furthermore, to investigate ANG-related acquisition of proliferative potency in fibroblasts, the correlation between ANG and alpha-smooth muscle actin (α-SMA) levels was evaluated.
In immunohistochemistry, ANG was strongly expressed in pterygium stroma with all of four severe phenotypes (with recurrence, active growth, thick body [T3] and marked vascularization [V3]), especially at the perivascular areas. There was a trend toward higher ANG expression in cultured fibroblasts of pterygia with severe phenotype, compared to those without and normal conjunctiva. However, pterygium body vascularity (V) had a weak association with ANG expression. Additionally, Western blotting revealed a significant positive correlation between the expression levels of α-SMA and ANG.
Overexpression of ANG in pterygium body fibroblasts might be involved in active pterygium growth with thick pterygium body formation and increased risk of recurrence. A possible mechanism for this finding includes ANG-related transition of pterygium fibroblasts to the proliferative state.
[show abstract][hide abstract] ABSTRACT: In type 2 diabetes mellitus (T2DM) patients, the gradual loss of pancreatic β-cell function is a characteristic feature of disease progression that is associated with sustained hyperglycemia. Recently, G protein-coupled receptor 119 (GPR119) has been identified as a promising anti-diabetic therapeutic target. It is predominantly expressed in pancreatic β-cells, directly promotes glucose stimulated insulin secretion and indirectly increases glucagon-like peptide 1 (GLP-1) levels reducing appetite and food intake. Activation of GPR119 leads to insulin release in β-cells by increasing intracellular cAMP. Here, we identified a novel structural class of small-molecule GPR119 agonists, HD0471042, consisting of substituted a 3-isopropyl-1,2,4-oxadiazol-piperidine derivative with promising potential for the treatment of T2DM. The GPR119 agonist, HD0471042 increased intracellular cAMP levels in stably human GPR119 expressing CHO cell lines and HIT-T15 cell lines, hamster β-cell line expressing endogenously GPR119. HD0471042, significantly elevated insulin release in INS-1 cells of rat pancreatic β-cell line. In in vivo experiments, a single dose of HD0471042 improved glucose tolerance. Insulin and GLP-1 level were increased in a dose-dependent manner. Treatment with HD0471042 for 6 weeks in diet induced obesity mice and for 4 weeks in ob/ob and db/db mice improved glycemic control and also reduced weight gain in a dose-dependent manner. These data demonstrate that the novel GPR119 agonist, HD0471042, not only effectively controlled glucose levels, but also had an anti-obesity effect, a feature observed with GLP-1. We therefore suggest that HD0471042 represents a new type of anti-diabetes agent with anti-obesity potential for the effective treatment of type 2 diabetes.
Archives of Pharmacal Research 07/2013; · 1.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130, and PGC-1α may attenuate the progression of diabetic nephropathy.
Biochemical and Biophysical Research Communications 05/2013; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The location of acetylcholinesterase-containing nerve fibers suggests a role for acetylcholine in both contractility and secretion in the prostate gland. The colocalization of nitrergic nerves with cholinergic nerves, and the cotransmission of nitric oxide with acetylcholine in cholinergic nerves, has been demonstrated in the prostate glands of various species. Thus, we investigated the effects of acetylcholine on phenylephrine-induced contraction and the correlation between cholinergic transmission and nitric oxide synthase by using isolated prostate strips of rabbits.
Isolated prostate strips were contracted with phenylephrine and then treated with cumulative concentrations of acetylcholine. Changes in acetylcholine-induced relaxation after preincubation with NG-nitroarginine methyl ester, 7-nitroindazole, and aminoguanidine were measured. The effects of selective muscarinic receptor antagonists were also evaluated.
In the longitudinal phenylephrine-contracted strip, the cumulative application of acetylcholine (10(-9) to 10(-4) M) elicited a concentration-dependent relaxation effect. Acetylcholine-induced relaxation was inhibited not only by nitric oxide synthase inhibitors (10 µM L-NAME or 10 µM 7-nitroindazole) but also by 10 µM atropine and some selective muscarinic receptor antagonists (10(-6) M 11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one and 10(-6) M 4-diphenylacetoxy-N-methyl-piperidine). In contrast, relaxation was significantly increased by pretreatment of the strips with 10 mM L-arginine.
Acetylcholine relaxed phenylephrine-induced contractions of isolated rabbit prostate strips. This relaxation may be mediated via both cholinergic and constitutive nitric oxide synthase with both the M2 and M3 receptors possibly playing key roles.
[show abstract][hide abstract] ABSTRACT: We tested the hypothesis that acute inflammation may cause arterial stiffening in older adults. We further explored if high cardiorespiratory fitness may partially prevent the unfavorable effect of arterial stiffening produced by acute systemic inflammation in older adults. Using a randomized double-blind sham placebo-controlled design, forty healthy older adults were assigned to receive either an influenza vaccine or a sham vaccine. C-reactive protein and interleukin 6 (IL-6) were measured as markers of inflammation. Carotid-femoral pulse wave velocity (PWV) and augmentation index (AIX) as indices of arterial stiffness and wave reflection were assessed at baseline and 24 and 48 h after each vaccination. When compared with sham placebo, the influenza vaccination caused a significant increase in CRP (p < 0.05) and IL-6 (p < 0.05). Carotid-femoral PWV, but not AIX was significantly increased after influenza vaccination (p < 0.05), but not sham vaccination. The high cardiorespiratory fitness group had an attenuated increase in PWV as compared to the low cardiorespiratory fitness group after acute inflammation (p < 0.05). These findings show that acute inflammation may cause significant increases in arterial stiffness in older adults, but these increases were attenuated in the high cardiorespiratory fitness group as compared to the low cardiorespiratory fitness group.
[show abstract][hide abstract] ABSTRACT: This study was designed to investigate the effects of α-defensin 1 on electrical field stimulation (EFS)-induced contractions in isolated rat bladder detrusor muscles. We evaluated the effects of α-defensin 1 (50pM∼5nM) on EFS-induced contractions in the detrusor smooth muscles from 35 rats (2-30Hz). Bladder strips were pretreated with α-defensin 1 and then changes of contractions by adenosine 5'-triphosphate (ATP) were observed. Moreover, after pretreatment with α-defensin 1 for 10minutes, changes in concentration-response curves to hydrogen peroxide (H2O2) were investigated. Alpha-defensin 1 has increased EFS-induced contractions, significantly, and the contractile response to ATP (1,2,5,10mM) was also increased significantly when strips were pretreated with α-defensin 1. In addition, alpha-defensin 1 increased H2O2-induced contractions. The present study demonstrates that α-defensin 1 increases EFS-induced contractions of rat detrusor muscles via purinergic contraction coupled with the Rho kinase pathway.
European journal of pharmacology 03/2013; · 2.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: A focal stimulus triggers neural activity that spreads to cortical regions far beyond the stimulation site, creating a so-called "cortical point spread" (CPS). Animal studies found that V1 neurons possess lateral connections with neighboring neurons that prefer similar orientations and to neurons representing visuotopic regions that are constrained by their preferred orientation axis. Although various roles in visual processing are proposed for this anatomical anisotropy of lateral connections, evidence for a corresponding "functional" anisotropy in CPS is lacking or inconsistent in animal studies and absent in humans. To explore functional anisotropy, we inspected axial constraints on CPS in human visual cortex using functional magnetic resonance imaging. We defined receptive fields (RFs) of unit gray matter volumes and delineated the spatial extents of CPS in visuotopic space. The CPS triggered by foveal stimuli exhibited coaxial anisotropy with larger spatial extents along the axis of stimulus orientation. Furthermore, the spatial extents of CPS along the coaxial direction increased with an increasing similarity of local sites to the CPS-inducing stimulus in orientation preference. From CPS driven by multifocal stimuli, the coaxially biased spread was also found in cortical regions in the periphery, albeit reduced in degree, and was invariant to a varying degree of radial relationship between stimuli and RF positions of local sites, rejecting radial bias as an origin of coaxial anisotropy. Our findings provide a bridge between the anatomical anisotropy seen in animal visual cortex and a possible network property supporting spatial contextual effects in human visual perception.
Journal of Neuroscience 01/2013; 33(3):1143-56. · 6.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ultrasound stimulation produces significant multifunctional effects that are directly relevant to alveolar bone formation, which is necessary for periodontal healing and regeneration. We focused to find out effects of specific duty cycles and the percentage of time that ultrasound is being generated over one on/off pulse period, under ultrasound stimulation. Low-intensity pulsed ultrasound ((LIPUS) 1 MHz) with duty cycles of 20% and 50% was used in this study, and human alveolar bone-derived mesenchymal stem cells (hABMSCs) were treated with an intensity of 50 mW/cm(2) and exposure time of 10 min/day. hABMSCs exposed at duty cycles of 20% and 50% had similar cell viability (O.D.), which was higher (*P < 0.05) than that of control cells. The alkaline phosphatase (ALP) was significantly enhanced at 1 week with LIPUS treatment in osteogenic cultures as compared to control. Gene expressions showed significantly higher expression levels of CD29, CD44, COL1, and OCN in the hABMSCs under LIPUS treatment when compared to control after two weeks of treatment. The effects were partially controlled by LIPUS treatment, indicating that modulation of osteogenesis in hABMSCs was related to the specific stimulation. Furthermore, mineralized nodule formation was markedly increased after LIPUS treatment than that seen in untreated cells. Through simple staining methods such as Alizarin red and von Kossa staining, calcium deposits generated their highest levels at about 3 weeks. These results suggest that LIPUS could enhance the cell viability and osteogenic differentiation of hABMSCs, and could be part of effective treatment methods for clinical applications.
BioMed research international. 01/2013; 2013:269724.
[show abstract][hide abstract] ABSTRACT: Background
Sasang typology is a personalized traditional medicine widely used in clinical diagnosis and treatment in Korea. The aim of this study was to examine the biopsychological personality profiles of traditional Korean Sasang typology in a clinical sample of Korean children.MethodsA total of 150 children were classified as one of three traditional Korean Sasang types (19 So-Yang, 118 Tae-Eum, and 13 So-Eum) by two clinical experts in Sasang typology. The childrens’ mothers completed the Korean version of the Junior Temperament and Character Inventory (JTCI). The four temperament dimensions of JTCI were compared between the different Sasang types using analysis of variance (ANOVA) and profile analysis.ResultsThere were no significant differences in age, gender, and parents’ education levels across the Sasang types. The JTCI temperament profile for each of the child Sasang types was significantly different (profile analysis, df = 5.315, F = 2.508, p = 0.027). There were significant differences in novelty-seeking (F = 3.850, p = 0.023) and novelty-seeking subscales, but not with other temperament dimensions.Conclusion
These results demonstrated distinct temperament traits associated with traditional Korean Sasang types in children using an objective biopsychological personality inventory. With further investigation into the biopsychological profiles of the children, the longitudinal stability of the Sasang typology can be examined.
Integrative Medicine Research. 12/2012; 1(1):21–25.
[show abstract][hide abstract] ABSTRACT: We examined renal kallikrein-kinin system (KKS) apoptosis and its related signaling pathway in rat podocytes. In addition, we studied the relationship of cannabinoid receptor 1 (CB(1)R) with high glucose and BK receptors.
Cell viability was determined by an MTT assay and apoptosis by DNA fragmentation assay, while gene expression was investigated by RT-PCR. Protein expression was analyzed by Western blot analysis. A chemical inhibitor or siRNA transfection was used to inhibit B1R, B2R, and CB(1)R signaling.
High glucose (25mM) treatment decreased cell viability and increased DNA fragmentation. High glucose-induced DNA fragmentation and PARP and caspase-3 activations were blocked by both [des-Arg(10)]-HOE 140 (a B1R antagonist) and HOE 140 (a B2R antagonist). High glucose also increased Akt phosphorylation, ER stress-related protein expression, and NF-κB/I-κB phosphorylation in podocytes, which was blocked by both [des-Arg(10)]-HOE 140 and HOE 140. In addition, B1R and B2R siRNA transfections prevented high glucose-induced Akt and NF-κB activations in rat podocytes. Moreover, AM251 (a CB(1)R antagonist) treatment and CB(1)R siRNA transfection blocked the high glucose-induced stimulation of BK receptor expression, Akt activation, and NF-κB activation.
Our study suggests that hyperglycemia induces apoptosis via the stimulation of B1R and B2R expression through CB(1)R activation in rat podocytes in vitro, which is associated with the development of diabetic nephropathy.
Life sciences 07/2012; 91(19-20):895-906. · 2.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this article, we describe the design and manipulation of charged nanomatrices and their application as efficient platforms for modulating cell behaviors. Using electrospraying technology and well designed biomaterials, poly(ɛ-caprolactone; PCL) and polyethylenimine, the negatively charged PCL nanomatrix (nPCL nanomatrix) and the positively charged PCL nanomatrix (pPCL nanomatrix) were fabricated. It was demonstrated that cell adhesion, affinity, and shape were sensitively modulated in negatively and positively charged nanomatrices. Our results showed that the pPCL nanomatrix promoted adhesion of NIH 3T3 fibroblast cells as compared to the nPCL nanomatrix. When fluid shear stress was applied, cell affinity on the pPCL nanomatrix increased even more. NIH 3T3 fibroblast cells adopted a relatively spherical shape on the pPCL nanomatrix while adopting an aligned, narrow shape on the nPCL nanomatrix. It was also found that charged nanomatrices influenced the cross-sectional cell shape. The cross-sectional cell shape on the pPCL nanomatrix was extremely flattened, whereas the cross-sectional cell shape was relatively round on the nPCL nanomatrix and some of the adhered cells floated. We also showed that the surfaces of the nPCL and pPCL nanomatrices adsorbed the different serum proteins. These results collectively demonstrated a combination of environmental factors including nanoscale structure, electrostatic forces, and absorption of biomolecules on charged substrates affected cell response in terms of cellular adhesion and shape.
Tissue Engineering Part C Methods 07/2012; 18(12):913-923. · 4.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: Understanding factors that contribute to changes in arterial stiffness over time is important as this may lead to therapies that can abrogate cardiovascular risk. We compared the contribution of pulsatile stress and inflammation to changes in arterial stiffness in middle-aged men using a 1-year follow-up study design.Methods: Arterial stiffness was derived from brachial-ankle pulse wave velocity (baPWV) in 107 men (mean age 53±6 yrs) on two separate occasions. The changes in outcome variables were calculated as the difference between the first and second examinations (mean interval 403±122 days). Pulsatile stress was calculated as the product of heart rate and brachial pulse pressure. C-reactive protein (CRP), white blood cell count (WBC) and fibrinogen were measured as inflammatory markers.Results: At baseline, baPWV was significantly correlated with pulsatile stress (r=0.37, p<0.01), WBC (r=0.19, p<0.05), HbA1c (r=0.39, p<0.01), HDL-C (r=.0.20, p<0.05), but not CRP (r= 0.06, p=0.56), or fibrinogen (r=0.12, p=0.21). The change in baPWV over 1 year was associated with the change in pulsatile stress (r=0.26, p<0.01) and HbA1c (r=0.19, p<0.05) over that same time period. Change in baPWV was not associated with the change in WBC (r=0.18, p=0.06) or CRP (r=0.05, p=0.62).Conclusions: These results demonstrate that both pulsatile stress and inflammation may be associated with arterial stiffness at any given moment in time, but change in pulsatile stress is a better predictor of change in arterial stiffness over time.
Journal of atherosclerosis and thrombosis 07/2012; · 2.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: Culturing corneal keratocytes is difficult because keratocytes growing in a monolayer rapidly lose their stellate morphology and cease to express keratocyte markers such as keratocan, lumican and aldehyde dehydrogenase 1 family, member A1 (ALDH1A1). Conversely, mesenchymal stem cells (MSCs) can be easily expanded in cell culture, and they have a variety of differentiation pathways. We studied the feasibility of using MSCs as a source for corneal tissue engineering. Based on the observation that keratocytes have MSC-like properties, similar to bone marrow-derived MSCs (BM-MSCs), we hypothesized that MSCs would differentiate into corneal keratocyte-like cells in keratocyte-conditioned medium (KCM). We measured changes in the expression of keratocyte markers through quantitative real-time polymerase chain reaction (qRT-PCR) and found that human MSC's cultured in KCM expressed both keratocan and ALDH1A1. Western blot analysis demonstrated that human MSCs cultured in KCM steadily increased their expression of lumican and ALDH1A1, while they lost expression of α-smooth muscle actin (α-SMA). Immunocytochemistry indicated that human MSCs grown in KCM acquired characteristics similar to those of keratocytes. These results suggest that KCM can direct human MSCs to differentiate into keratocyte-like cells.
Experimental Eye Research 06/2012; 101:16-26. · 3.03 Impact Factor