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Ke-Hung Chien, Shih-Jen Chen,
Jorn-Hon Liu,
Lin-Chung Woung,
Jiann-Torng Chen,
Chang-Min Liang,
Shih-Hwa Chiou,
Ching-Yao Tsai,
Cheng-Kuo Cheng,
Chao-Chien Hu,
Chi-Hsien Peng
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ABSTRACT: : MicroRNA-145 (miR-145) has known anti-tumor properties and has been reported to be involved in regulating corneal epithelium differentiation. The exact role of miR-145 in ocular tissue remains unclear. In this study, we evaluate the effect of miR-145 expression levels on pterygium properties.
: Ophthalmology department of a tertiary medical center.
: Case series study.
: Information regarding patient age, pterygium recurrence and pterygium severity (extension [E], vascularity [V] and thickness [T]) were gathered from records. Expression levels of miR-145 were obtained through examination of excised pterygium tissue. Correlations between age, pterygium classification, and miR-145 levels were evaluated.
: This study evaluated 253 patients (mean age 54.1±10.8 years). As pterygium severity increased, miR-145 levels decreased. Negative correlations were also found between miR-145 expression levels and pterygium extension (E) and vascularity (V). Thickness (T) had a weak negative correlation. There was only a mild negative correlation between patient age and miR-145 levels, which was only seen in patients with primary pterygium (not recurrent ones). Additionally, miR-145 expression was significantly higher in primary samples than in recurrent ones.
: We demonstrated an association between miR-145 and pterygium characteristics, consistent with its known tumor suppression effect. Because the management of pterygium is often difficult, we suggest that miR-145 should be further studied as a potential treatment.
The ocular surface 04/2013; 11(2):133-8. · 3.93 Impact Factor
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Der-Chong Tsai,
Chin-Chou Huang, Shih-Jen Chen,
Pesus Chou,
Chia-Min Chung,
Wan-Leong Chan,
Po-Hsun Huang,
Tseng-Ji Chen,
Shing-Jong Lin,
Jaw-Wen Chen,
Hsin-Bang Leu
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ABSTRACT: BACKGROUND: Central serous chorioretinopathy (CSCR) is a common maculopathy that features choroidal circulatory disturbance. This population-based cohort study aimed to explore the relationship between CSCR and the future development of ischaemic stroke. METHODS: Data were obtained from Taiwan's national health insurance research database. From 2000 to 2007, 1814 patients with newly diagnosed CSCR were eligible for inclusion in the study cohort. Using stratified random sampling, 9648 enrollees matched with the study subjects in terms of sex, age, monthly income, geographical location and time of enrolment were selected as the control group. Stroke-free survival analysis was assessed using a Kaplan-Meier method. Cox proportional hazard regressions were performed to calculate the HR of ischaemic stroke for the two groups after adjusting for possible confounding variables. RESULTS: Of the sampled patients, 45 (2.5%) from the CSCR cohort and 157 (1.6%) from the control group developed ischaemic stroke during a mean follow-up period of 3.9±2.2 years. CSCR patients had a significantly higher incidence of ischaemic stroke than those without a diagnosis of CSCR (p=0.003). After adjusting for age, sex and chronic comorbidities at baseline, CSCR patients were found to have a 1.56-fold (95% CI 1.11 to 2.18, p=0.010) greater risk of a subsequent ischaemic stroke than the matched controls. CONCLUSIONS: CSCR is an independent indicator for the increased risk of subsequent ischaemic stroke development.
The British journal of ophthalmology 09/2012; · 2.92 Impact Factor
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ABSTRACT: Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44+proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage.
Biomaterials 07/2012; 33(32):8003-16. · 7.40 Impact Factor
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ABSTRACT: To assess the prevalence and associated risk factors of myopic maculopathy in an elderly Chinese population in Taiwan.
Population-based, cross-sectional study. A total of 1361 Chinese aged 65 years or older residing in Shihpai, Taipei, Taiwan, underwent a detailed ophthalmic examination. Of the 1361 participants, 1058 subjects had at least one gradable fundus photograph and were recruited for analysis. High myopia was defined as spherical equivalent of less than -6.0 diopter (D) in the phakic eyes or axial length greater than 26.5 mm in pseudophakic or aphakic eyes. Myopic maculopathy was defined as the appearance of lacquer cracks, focal area of deep choroidal atrophy and macular choroidal neovascularization, or geographic atrophy in the presence of high myopia.
The prevalence of high myopia was 4.2% (44/1058). Signs of myopic maculopathy were present in 32 (72.7%) of the 44 high myopics, representing a prevalence of 3.0% (95% confidence interval, 2.0%-4.0%). Subjects with high myopia with myopic maculopathy had higher systolic blood pressure than those without maculopathy (146.4 ± 16.2 mm Hg vs. 127.0 ± 15.9 mm Hg, P = 0.001), and the difference persisted (P = 0.018) after adjustment for age, sex, smoking, body mass index, diastolic blood pressure, educational levels, alcohol drinking, and histories of diabetes or taking anti-hypertension medication. Of the 65 high myopic eyes, eyes with maculopathy had a greater myopic degree (-12.8 ± 5.1 D vs. -7.6 ± 1.5 D, P = 0.001) and poorer corrected visual acuity (logMAR 0.72 ± 0.6 vs. 0.27 ± 0.2, P = 0.001) than those without.
The prevalence of high myopia and myopic maculopathy in this elderly Chinese population group was high. Of the major risk factors examined, high systolic blood pressure may be associated with myopic maculopathy.
Investigative ophthalmology & visual science 06/2012; 53(8):4868-73. · 3.43 Impact Factor
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Chi-Hsien Peng,
Jorn-Hon Liu,
Lin-Chung Woung,
Tzu-Jung Lin,
Shih-Hwa Chiou,
Po-Chen Tseng,
Wen-Yuan Du,
Cheng-Kuo Cheng,
Chao-Chien Hu,
Ke-Hung Chien, Shih-Jen Chen
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ABSTRACT: Let-7 microRNA is an important regulator of cellular ageing and tissue senescence. The objective of this study is to evaluate the expression of let-7a/let-7b/let-7c microRNAs in human age-related cataracts.
To evaluate the correlation among the severity of lens opacity, the level of let-7a/let-7b/let-7c microRNA expression and patient age in the context of age-related cataracts.
The authors evaluated the mRNA level of let-7a/let-7b/let-7c microRNA in lens epithelia obtained from 174 eyes with age-related cataracts. The authors also recorded the patient age and the severity of lens opacity as classified according to the modified version of the Lens Opacities Classification System version III.
Let-7b microRNA expression was demonstrated to be positively associated with patient age (R=0.472; p<0.001). A positive correlation was also observed between higher N, C and P cataract scores and higher expression of let-7b microRNA in patients with age-related cataracts (p<0.001). However, no significant correlation was observed between the let-7a and let-7c microRNA expression levels and either the severity of lens opacity or the patient age.
These findings suggest that microRNAs play a role in age-related cataracts. A local let-7b microRNA increase may represent a risk factor in the formation of age-related cataracts.
The British journal of ophthalmology 02/2012; 96(5):747-51. · 2.92 Impact Factor
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ABSTRACT: Vascular progenitor cells (VPCs) are a heterogeneous population, containing a subpopulation co-expressing both endothelial and smooth muscle phenotypes. This study sought to determine whether the level of this subpopulation correlated with the coronary Gensini score.
VPCs were cultivated in 50 patients undergoing coronary angiography. A subpopulation of VPCs expressed both endothelial (VE-cadherin [VE-Cad]) and smooth-muscle phenotypes (α-smooth muscle actin [α-SMA]). Correlations of the VE-Cad(low)α-SMA(+) VPC level and adhesion molecule expression by VPCs with the Gensini score were investigated. The association between the amount of this subpopulation and the development of intimal hyperplasia (IH) was also estimated in a vascular injury animal model. Both the number of VE-Cad(low)α-SMA(+) VPCs (P = 0.002) and the expression level of intracellular adhesion molecule (ICAM)-1 by VPCs (P = 0.008) correlated with the Gensini score. However, only the number of VE-Cad(low)α-SMA(+) VPCs (P = 0.004) and the blood level of low-density lipoprotein cholesterol (P = 0.016) were parameters independently associated with the Gensini score in multivariate analysis. Furthermore, in an animal model of injecting VPCs into SCID mice after femoral artery wire injury, a higher number of VE-Cad(low)α-SMA(+) VPCs correlated with greater IH (r = 0.69, P<0.0001).
The level of VE-Cad(low)α-SMA(+) VPCs was associated with the severity of coronary atherosclerosis as quantified by the Gensini score. Manipulating this subpopulation may provide a way of attenuating atherosclerosis in the future.
Circulation Journal 12/2011; 76(2):477-84. · 3.77 Impact Factor
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ABSTRACT: To investigate age-related trends in refractive, corneal, and internal astigmatism and to assess the association between internal astigmatism and lens opacity in an elderly Chinese population.
A population-based study was conducted among 1360 inhabitants aged 65 years and older in Taipei, Taiwan. Participants underwent measurements of refraction, corneal dioptric power, and slit lamp biomicroscopy with lens grading. A total of 2084 eyes were included in power vector analyses of Cartesian astigmatism (J(0)) and oblique astigmatism (J(45)) components of refractive, corneal, and internal astigmatism.
The crude prevalence of refractive astigmatism (defined as ≥0.75 diopters) was 73.0% based on the right eyes and 76.4% based on the left eyes. The vector values in both refractive J(0) and corneal J(0) tended to be more negative with increasing age (P < 0.001), indicating the trend toward against-the-rule (ATR) astigmatism. Corneal J(0) alone accounted for 54% of the variability in refractive J(0). Refractive J(45) increased with age in the right eyes (P < 0.001) and decreased slightly with age in the left eyes (P = 0.012). Cortical opacity was associated with internal J(0) (P = 0.025), but the association was weak.
Astigmatism affects approximately three quarters of the Chinese population aged 65 years and older in Taiwan. With increasing age, the prevalence of astigmatism increases, and refractive and corneal astigmatism shift toward ATR. Continuous corneal changes appear to be responsible for the age trend in refractive astigmatism. The severity of lens opacity plays only a minor role in the change of internal astigmatism.
Investigative ophthalmology & visual science 11/2011; 52(13):9651-7. · 3.43 Impact Factor
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Chi-Hsien Peng,
Jong-Yuh Cherng,
Guang-Yuh Chiou,
Yu-Chih Chen,
Chen-Hsiu Chien,
Chung-Lan Kao,
Yuh-Lih Chang,
Yueh Chien,
Liang-Kung Chen,
Jorn-hon Liu, Shih-Jen Chen,
Shih-Hwa Chiou
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ABSTRACT: Cationic polyurethane, a biodegradable non-viral vector, protects DNA from nuclease degradation and helps to deliver genes efficiently. Oct4, a POU-domain transcription factor, is highly expressed in maintaining pluripotency and cellular reprogramming process in stem cells. SirT1, a NAD-dependent histone deacetylase, is an essential mediator of cellular longevity. Herein we demonstrated that both Oct4 and SirT1 (Oct4/SirT1) expression was decreased in an age-dependent manner in retina with aged-related macular degeneration and retinal pigment epithelium cells (RPEs). To investigate the possible rescuing role of Oct4/SirT1, polyurethane-short branch polyethylenimine (PU-PEI) was used to deliver Oct4/SirT1 into aged RPEs (aRPEs) or light-injured rat retinas. Oct4/SirT1 overexpression increased the expression of several progenitor-related genes and the self-renewal ability of aRPEs. Moreover, Oct4/SirT1 overexpression resulted in the demethylation of the Oct4 promoter and enhanced the expression of antioxidant enzymes, which was accompanied by a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Importantly, PU-PEI-mediated Oct4/SirT1 gene transfer rescued retinal cell loss and improved electroretinographic responses in light-injured rat retinas. In summary, these data suggest that PU-PEI-mediated delivery of Oct4/SirT1 reprograms aRPEs into a more primitive state and results in cytoprotection by regulating the antioxidative capabilities of these cells.
Biomaterials 09/2011; 32(34):9077-88. · 7.40 Impact Factor
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ABSTRACT: To evaluate the correlation between the severity of lens opacity, patient age, and the level of silent information regulator T1 (SirT1) expression in the lens epithelium of age-related cataracts.
Department of Ophthalmology, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
Case control study.
Patient age at the time of cataract surgery and lens opacity severity, classified using the modified version of the Lens Opacities Classification System III (LOCS III), were recorded. Lens epithelium samples were obtained, and the expression level of SirT1 mRNA was evaluated.
The study evaluated 233 eyes with cataract. Older patients had higher nuclear (N), cortical (C), and posterior subcapsular (P) cataract LOCS III scores. The expression of SirT1 in lens opacity was significantly less in patients 51 years and older than in those younger than 51 years. The level of SirT1 expression was significantly negatively associated with patient age (r = -0. 746, P < .001). A significant correlation was also found between a higher N, C, and P cataract score and lower expression of SirT1 in patients with age-related cataract (P < .001).
The decreased expression of SirT1 in the lens epithelium was associated with higher cataract scores and patient age. The results suggest that a local SirT1 decrease in cataractous lens could be a risk factor for the initiation of age-related cataract formation.
Journal of cataract and refractive surgery 07/2011; 37(7):1270-4. · 2.75 Impact Factor
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Yuh-Lih Chang,
Shih-Jen Chen,
Chung-Lan Kao,
Shih-Chieh Hung,
Dah-Ching Ding,
Cheng-Chia Yu, Yi-Jen Chen,
Hung-Hai Ku,
Chin-Po Lin,
Kun-Hsiung Lee,
Yu-Chih Chen,
Jhi-Joung Wang,
Chuan-Chih Hsu,
Liang-Kung Chen,
Hsin-Yang Li,
Shih-Hwa Chiou
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ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic (DA) neurons in the midbrain. Induced pluripotent stem (iPS) cells have shown potential for differentiation and may become a resource of functional neurons for the treatment of PD. However, teratoma formation is a major concern for transplantation-based therapies. This study examined whether functional neurons could be efficiently generated from iPS cells using a five-step induction procedure combined with docosahexaenoic acid (DHA) treatment. We demonstrated that DHA, a ligand for the RXR/Nurr1 heterodimer, significantly activated expression of the Nurr1 gene and the Nurr1-related pathway in iPS cells. DHA treatment facilitated iPS differentiation into tyrosine hydroxylase (TH)-positive neurons in vitro and in vivo and functionally increased dopamine release in transplanted grafts in PD-like animals. Furthermore, DHA dramatically upregulated the endogenous expression levels of neuroprotective genes (Bcl-2, Bcl-xl, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor) and protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis in iPS-derived neuronal precursor cells. DHA-treated iPS cells significantly improved the behavior of 6-hydroxydopamine (6-OHDA)-treated PD-like rats compared to control or eicosapentaenoic acid-treated group. Importantly, the in vivo experiment suggests that DHA induces the differentiation of functional dopaminergic precursors and improves the abnormal behavior of 6-OHDA-treated PD-like rats by 4 months after transplantation. Furthermore, we found that DHA treatment in iPS cell-grafted rats significantly downregulated the mRNA expression of embryonic stem cell-specific genes (Oct-4 and c-Myc) in the graft and effectively blocked teratoma formation. Importantly, 3 Tesla-magnetic resonance imaging and ex vivo green fluorescence protein imaging revealed that no teratomas were present in transplanted grafts of DHA-treated iPS-derived DA neurons 4 months after implantation. Therefore, our data suggest that DHA plays a crucial role in iPS differentiation into functional DA neurons and that this approach could provide a novel therapeutic approach for PD treatment.
Cell Transplantation 06/2011; 21(1):313-32. · 5.13 Impact Factor
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ABSTRACT: The aim of this study was to investigate the relations of left ventricular (LV) mass and geometry to LV function in patients with predialysis chronic kidney disease (CKD), by real-time 3-dimensional echocardiography (RT3-DE).
Echocardiography was performed on 76 consecutively enrolled patients (51 men) with different stages of CKD, including 26 patients with mild CKD (CKD stages 1-2) and 50 patients with moderate-to-severe CKD (CKD stages 3-5). LV mass and LV end-diastolic volume were measured by RT3-DE.
Greater prevalence of LV diastolic dysfunction and higher mitral E/myocardial velocities in early diastole (Em) values were noted in patients with moderate-to-severe CKD. In the moderate-to-severe CKD group, patients with increased LV mass had lower myocardial velocities in peak systole (Sm) and longer isovolumic relaxation time (IVRT). In the mild CKD group, patients with increased LV mass to volume ratios had lower Em. Moderate-to-severe CKD was associated with lower Sm and Em and higher mitral rapid filling to Em (E/Em) ratios by LV mass quartile stratification. Using LV mass/volume quartile stratification, moderate-to-severe CKD was associated with longer IVRT, lower Sm and higher mitral E/Em. Multivariable logistic regression analysis showed that CKD severity was the most independent predictor of elevated LV filling pressure (odds ratio = 2.96, p=0.019).
Increased LV mass impaired LV contraction and relaxation in patients with moderate-to-severe CKD. Concentric remodeling impaired LV diastolic function in patients with mild CKD. CKD severity was positively associated with elevated LV filling pressure.
Journal of nephrology 05/2011; 25(1):96-106. · 1.65 Impact Factor
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Hsin-Yang Li,
Yi-Jen Chen, Shih-Jen Chen,
Chung-Lan Kao,
Ling-Ming Tseng,
Wen-Liang Lo,
Chia-Ming Chang,
Der-Ming Yang,
Hung-Hai Ku,
Nae-Fang Twu,
Chen-Yi Liao,
Shih-Hwa Chiou,
Yuh-Lih Chang
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ABSTRACT: Studies have demonstrated that mesenchymal stem-like cells can be isolated from endometrium. However, the potential of endometrial-derived stem cells to differentiate into insulin-positive cells and functionally secrete insulin remains undetermined. We isolated endometrial mesenchymal stem-like cells (EMSCs) from human endometrial tissue from six donors. The insulin-secreting function of EMSCs was further analyzed in vitro and in transplanted grafts in vivo. We successfully isolated EMSCs from human endometrium, and our results showed that EMSCs expressed high levels of stemness genes (Nanog, Oct-4, Nestin). Under specific induction conditions for 2 weeks, EMSCs formed three-dimensional spheroid bodies (SBs) and secreted C-peptide. The high insulin content of SB-EMSCs was confirmed by enzyme-linked immunosorbent assay, and glucose responsiveness was demonstrated by measuring glucose-dependent insulin secretion. Using cDNA microarrays, we found that the expression profiles of SB-EMSCs are related to those of islet tissues. Insulin and C-peptide production in response to glucose was significantly higher in SB-EMSCs than in undifferentiated EMSC controls. Furthermore, upon differentiation, SB-EMSCs displayed increased mRNA expression levels of NKx2.2, Glut2, insulin, glucagon, and somatostatin. Our results also showed that SB-EMSCs were more resistant to oxidative damage and oxidative damage-induced apoptosis than fibroblasts from the same patient. It is noteworthy that SB-EMSCs xenotransplanted into immunocompromised mice with streptozotocin-induced diabetes restored blood insulin levels to control values and greatly prolonged the survival of graft cells. These data suggest that EMSCs not only play a novel role in the differentiation of pancreatic progenitors, but also can functionally enhance insulin production to restore the regulation of blood glucose levels in an in vivo transplantation model.
Journal of Pharmacology and Experimental Therapeutics 12/2010; 335(3):817-29. · 3.83 Impact Factor
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Hsiang-Yu Lin,
Cheng-Hung Huang,
Hsiao-Chi Yu,
Kah-Wai Chong,
Ju-Hui Hsu,
Pi-Chang Lee,
Kang-Hsiang Cheng,
Chuan-Chi Chiang,
Huey-Jane Ho,
Shuan-Pei Lin, Shih-Jen Chen,
Po-Kang Lin,
Dau-Ming Niu
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ABSTRACT: Newborn screening for Fabry disease in Taiwan Chinese has revealed a high incidence of the late-onset GLA mutation IVS4 + 919G→A (∼1 in 1,500-1,600 males). We studied 94 adults with this mutation [22 men, 72 women; mean age: men 57.8 ± 6.0 (range 42-68), women 39.1 ± 14.1 years (range 19-82)]. Plasma α-galactosidase A activity assay was 10.4 ± 11.2% of normal in the men and 48.6 ± 19.5% of normal in the women. Echocardiography in 90 of the adults revealed left ventricular hypertrophy (LVH) in 19 (21%), including 14 of 21 men (67%) and 5 of 69 women (7%). Microalbuminuria, based on the urine albumin-to-creatinine ratio measured on at least two occasions, was present in 17 of 86 subjects (20%) (men: 5/20, 25%; women 12/66, 18%). At least one ocular manifestation consistent with Fabry disease was present in 41 of 52 subjects (79%) who underwent ophthalmologic examination, including 8 (15%) with conjunctival vessel tortuosity, 15 (29%) with cornea verticillata, 10 (19%) with Fabry cataract, and 34 (65%) with retinal vessel tortuosity. Among subjects over 40 years of age, men were more likely than women to have LVH [14/21 (67%) vs 5/25 (20%), p < 0.001]. Cardiovascular, renal and ocular abnormalities are highly prevalent in adult Taiwan Chinese subjects with the Fabry mutation IVS4 + 919G→A. Our findings contribute to the limited understanding of the course of this late-onset disease variant and underscore the need for close follow up in such patients.
Journal of Inherited Metabolic Disease 10/2010; 33(5):619-24. · 3.58 Impact Factor
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ABSTRACT: Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential mediator of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including transcription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)-induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress.
SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardiac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activation on oxidative stress-induced aging, senescence-associated β-galactosidase (SA-β-gal) expression in RV-treated human umbilical vein endothelial cells (HUVECs) with or without H(2)O(2) treatment was evaluated.
SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-dependently increased in RV-treated HUVECs. The SA-β gal assay showed that RV inhibited the senescent phenotype of H(2)O(2)-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-β gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H(2)O(2)-treated HUVECs by siRNA-SirT1.
Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.
Journal of atherosclerosis and thrombosis 09/2010; 17(9):970-9. · 2.69 Impact Factor
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ABSTRACT: Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital cataracts, dental anomalies and mental retardation. The disease has been linked to a novel gene termed NHS located at Xp22.13. The majority of pathogenic mutations of the disease include nonsense mutations and small deletions and insertions that lead to truncation of the NHS protein. In this study, we identified a microdeletion of ∼ 0.92 Mb at Xp22.13 detected by array-based comparative genomic hybridization in two brothers presenting congenital cataract, dental anomalies, facial dysmorphisms and mental retardation. The deleted region encompasses the REPS2, NHS, SCML1 and RAI2 genes, and was transmitted from their carrier mother who presented only mild cataract. Our findings are in line with several recent case reports to indicate that genomic rearrangement involving the NHS gene is an important genetic etiology underlying NHS.
Journal of Human Genetics 09/2010; 56(1):8-11. · 2.57 Impact Factor
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Shih-Jen Chen,
Chia-Ming Chang,
Shen-Kou Tsai,
Yuh-Lih Chang,
Shih-Jie Chou,
Shiang-Suo Huang,
Lung-Kuo Tai,
Yu-Chih Chen,
Hung-Hai Ku,
Hsin-Yang Li,
Shih-Hwa Chiou
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ABSTRACT: Ischemic stroke is the leading cause of disability in the world. Cell transplantation has emerged in various neurological diseases as a potential therapeutic approach in the postacute stroke phase. Recently, inducible pluripotent stem (iPS) cells showed potential for multilineage differentiation and provide a resource for stem cell-based therapies. However, whether iPS transplantation could improve the function of stroke-like model is still an open question. The aim of this study is to investigate the therapeutic effects of subdural transplantation of iPS mixed with fibrin glue (iPS-FG) on cerebral ischemic rats induced by middle cerebral artery occlusion (MCAO). We demonstrated an efficient method to differentiate iPS into astroglial-like and neuron-like cells which display functional electrophysiological properties. In vivo study firstly showed that the direct injection of iPS into damaged areas of rat cortex significantly decreased the infarct size and improved the motor function in rats with MCAO. Furthermore, we found that the subdural iPS-FG can also effectively reduce the total infarct volume and greatly improve the behavior of rats with MCAO to perform rotarod and grasping tasks. Importantly, analysis of cytokine expression in iPS-FG-treated ischemic brains revealed a significant reduction of pro-inflammatory cytokines and an increase of anti-inflammatory cytokines. Taken together, these results suggest that iPS cells could improve the motor function, reduce infarct size, attenuate inflammation cytokines, and mediate neuroprotection after ischemic stroke. Subdural iPS-FG could be considered as a more safe approach because this method can avoid iatrogenic injury to brain parenchyma and enhance recovering from stoke-induced impairment.
Stem cells and development 03/2010; 19(11):1757-67. · 4.15 Impact Factor
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ABSTRACT: MafA is a pancreatic transcriptional factor that controls β-cell-specific transcription of the insulin gene. However, the role of MafA in the regulation of pancreatic transdifferentiation and reprogramming in human stem cells is still unclear. In this study, we investigate the role of MafA in placenta-derived multipotent stem cells (PDMSCs) that constitutively expressed Oct-4 and Nanog. PDMSCs were isolated and transfected with MafA using a lentivector. Our results showed that overexpression of MafA in PDMSCs significantly up-regulated the expression of pancreatic development-related genes (Sox17, Foxa2, Pdx1 and Ngn3). Microarray analysis suggested that the gene expression profile of MafA-overexpressing PDMSCs was similar to that of pancreas and islet tissues. MafA increased the expression levels of the mRNAs of NKx2.2, Glut2, insulin, glucagons and somatostatin, and further facilitated the differentiation of PDMSCs into insulin(+) cells. The glucose-stimulated responses to insulin and c-peptide production in MafA-overexpressing PDMSCs were significantly higher than in PDMSCs with vector control. Our results indicated that MafA-overexpressing PDMSCs were more resistant to oxidative damage and oxidative damage-induced apoptosis than PDMSCs carrying the vector control were. Importantly, the expression of MafA in PDMSCs xenotransplanted into immunocompromised mice improved the restoration of blood insulin levels to control values and greatly prolonged the survival of graft cells in immunocompromised mice with STZ-induced diabetes. In summary, these data suggest that MafA plays a novel role in the reprogramming of stem cells into pancreatic β-progenitors, promotes the islet-like characteristics of PDMSCs, as well as functionally enhances insulin production to restore the regulation of blood glucose levels in transplanted grafts.
Journal of Cellular and Molecular Medicine 02/2010; 15(3):612-24. · 4.13 Impact Factor
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ABSTRACT: Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs) derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson's disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS), reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases.
International Journal of Molecular Sciences 01/2010; 11(5):2039-55. · 2.60 Impact Factor
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ABSTRACT: Patients with vestibular hypofunction often experience dizziness and unsteadiness while moving their heads. Appropriate sensors can effectively detect a patient's dynamic visual acuity and associated body balance control. Forty-one vestibular-deficit patients and 10 normal individuals were invited to participate in this study. Questionnaires, clinical assessment scales and objective measures were evaluated on participants' first visits. After 12 sessions of training, all scales were evaluated again on vestibular-deficit patients. The computerized system was composed of sensors, including a gyro and strain gauges, data acquisition accessories and LabVIEW software. Results revealed that the system could effectively distinguish normal subjects from subjects with vestibular deficits. In addition, after a rehabilitation program, subjects' subjective and objective performances were significantly improved. Based on our results, we concluded that the present system, which uses a gyro and strain gauges, may provide an effective method for assessing and treating vestibular-deficit patients.
Sensors 01/2010; 10(8):7602-20. · 1.74 Impact Factor
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Chi-Hsien Peng,
Yuh-Lih Chang,
Chung-Lan Kao,
Ling-Ming Tseng,
Chih-Chia Wu,
Yu-Chih Chen,
Ching-Yao Tsai,
Lin-Chung Woung,
Jorn-Hon Liu,
Shih-Hwa Chiou, Shih-Jen Chen
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ABSTRACT: Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1), a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H(2)O(2) treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H(2)O(2)-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1). SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.
Sensors 01/2010; 10(6):6172-94. · 1.74 Impact Factor
