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Hsin-Yi Chen

Publications and source records attributed to Hsin-Yi Chen.

14 recordsLinked to original sources
PubMed2025

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗
PubMed2007

Rule extraction for glaucoma detection with summary data from StratusOCT.

PURPOSE: To extract and induce rules of association for differentiating between normal and glaucomatous eyes based on the quantitative assessment of summary data reports from the StratusOCT (optical coherence tomography; Carl Zeiss Meditec, Inc., Dublin, CA) in a Taiwan Chinese population. METHODS: One randomly selected eye of each of the 64 patients with glaucoma and each of the 71 normal subjects was included in the study. Measurements of glaucoma variables (retinal nerve fiber layer thickness and optic nerve head analysis results) were obtained with the StratusOCT. A self-organizing map and decision tree were applied to extract features and determine rules of association for glaucoma detection. RESULTS: The average visual field mean deviation was -0.55 +/- 0.57 dB in the normal group and -4.30 +/- 3.32 dB in the glaucoma group. Vertical cup-to-disc (C/D) ratio and inferior quadrant thickness were extracted from the decision tree, and three association rules were determined for glaucoma detection. CONCLUSIONS: The precise rules of association induced by a novel application of the decision tree may enhance glaucoma detection.

Adult↗
PubMed2006

Effects of domestic processing on steroidal saponins in Taiwanese yam cultivar (Dioscorea pseudojaponica Yamamoto).

The effects of domestic processing on steroidal saponins and furostanol and spirostanol glycosides in Taiwanese yam cultivar (Dioscorea pseudojaponica Yamamoto) were studied. The baking or frying of yam slices was conducted at 150, 180, and 200 degrees C for 3, 5, and 10 min. Yam slices were steamed or microwave cooked at 2450 MHz with an output power of 850 W for 3, 5, and 10 min. The various saponins were quantified by HPLC with an evaporative light scattering detector (ELSD). Results showed that the contents of saponins were decreased along with increasing cooking temperature and time except for the steaming treatment. None of the steamed yam slices significantly change their initial compositions or quantities of furostanol and spirostanol glycosides. Fried yam slices had the highest loss of saponins, especially at 200 degrees C for 10 min (93 and 97% reductions for total furostanol and spirostanol glycosides, respectively). After baking for 10 min at 200 degrees C, the total furostanol and spirostanol glycosides were reduced by 67 and 74%, respectively. There were 12, 44, and 84% decreases for total furostanol glycosides and 10, 35, and 75% reductions for total spirostanol glycosides in yam slices after microwave cooking for 3, 5, and 10 min, respectively. Diosgenin, the aglycone of these saponins, could be found in yams after microwave cooking and baking, but not in steamed and fried yams.

Dioscorea↗
PubMed2006

Structure-based drug design of a novel family of PPARgamma partial agonists: virtual screening, X-ray crystallography, and in vitro/in vivo biological activities.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is well-known as the receptor of thiazolidinedione antidiabetic drugs. In this paper, we present a successful example of employing structure-based virtual screening, a method that combines shape-based database search with a docking study and analogue search, to discover a novel family of PPARgamma agonists based upon pyrazol-5-ylbenzenesulfonamide. Two analogues in the family show high affinity for, and specificity to, PPARgamma and act as partial agonists. They also demonstrate glucose-lowering efficacy in vivo. A structural biology study reveals that they both adopt a distinct binding mode and have no H-bonding interactions with PPARgamma. The absence of H-bonding interaction with the protein provides an explanation why both function as partial agonists since most full agonists form conserved H-bonds with the activation function helix (AF-2 helix) which, in turn, enhances the recruitment of coactivators. Moreover, the structural biology and computer docking studies reveal the specificity of the compounds for PPARgamma could be due to the restricted access to the binding pocket of other PPAR subtypes, i.e., PPARalpha and PPARdelta, and steric hindrance upon the ligand binding.

Adipocytes↗
PubMed2006

Stratus optical coherence tomography for evaluating optic disc pits associated with maculopathy before and after vitrectomy: two case reports.

Optic disc pit (ODP) can be either congenital or acquired. Congenital ODP is typically unilateral, and the visual acuity and visual field are normal unless associated with macular serous detachment, which occurs in about 25-75% of cases. Acquired ODP is known as an important risk factor for progressive visual field loss in glaucoma. The fundus finding of congenital ODP includes oval depression involving the optic disc, with or without macular serous detachment. We used third-generation Stratus optical coherence tomography (Straus OCT) to investigate the possible pathogenesis of ODP associated with maculopathy and to monitor the anatomic changes before and after treatment.

Adolescent↗
PubMed2006

Logistic regression analysis for glaucoma diagnosis using Stratus Optical Coherence Tomography.

PURPOSES: The purposes of this study are to investigate the diagnostic performance of logistic regression analysis (LRA) applied to multidimensional information on glaucoma disease and to determine the area under receiver operator characteristic curves (AROCs) for differentiating between normal and glaucomatous eyes in the Taiwan Chinese population based on the summary data from the Stratus Optical Coherence Tomography (OCT). METHODS: One randomly selected eye from each of the 89 patients with glaucoma and from each of the 88 age- and gender-matched normal individuals were included in the study. Nine glaucomatous eyes and eight normal eyes were excluded as a result of poor OCT scans. Finally, 80 normal eyes and 80 glaucomatous eyes (mean deviation, -4.5 +/- 4.12 dB) were analyzed. The whole dataset was split into four equal sets. Each set combines 20 patients with glaucoma and 20 normal individuals. Fourfold crossvalidation was conducted. Retinal nerve fiber layer thickness and optic nerve head were measured by Stratus OCT in each patient. Twenty-five OCT parameters were included in a LRA method to determine the best combination of parameters for discriminating between glaucomatous and healthy eyes based on AROCs. RESULTS: With the LRA method, the AROC for glaucoma detection was 0.911 with sensitivity at 80% and 90% specificity were 83.7% and 80.0%, respectively. CONCLUSIONS: Compared with the OCT-provided parameters, the LRA method improved the ability to differentiate between normal and glaucomatous eyes in the Taiwan Chinese population.

Adolescent↗
PubMed2005

Discrimination between normal and glaucomatous eyes using Stratus optical coherence tomography in Taiwan Chinese subjects.

BACKGROUND: We differentiated between normal and glaucomatous eyes in the Taiwan Chinese population based solely on the quantitative assessment of summary data reports from Stratus optical coherence tomography (OCT) by comparing their area under the receiver operating characteristic (ROC) curve. METHODS: One randomly selected eye from each of the 62 patients with early glaucomatous damage (mean deviation -2.8 +/- 1.8 dB) and from each of the 62 age- and sex-matched normal individuals were included in the study. Measurements of glaucoma variables (retinal nerve fiber layer thickness and optic nerve head analysis results) were obtained by Stratus OCT. Twenty-one OCT parameters were included in a linear discriminant analysis (LDA) using forward selection and backward elimination to determine the best combination of parameters for discriminating between glaucomatous and healthy eyes based on ROC curve area. RESULTS: The average RNFL thickness was the best individual parameter for differentiating between normal eyes and glaucomatous eyes (ROC curve area 0.793). The maximum area under the ROC curve of six input parameters (average RNFL thickness; 10, 11, and 12 o'clock segment thicknesses; cup area; and vertical integrated rim area) generated by the forward selection method was 0.881. Whereas the maximum area under the ROC curve of 15 input parameters (average RNFL thickness; 1, 3, 4, 6, 8-10, 12 o'clock segment thicknesses; vertical integrated rim area; horizontal integrated rim area; disc area; cup to disc area ratio; cup to disc horizontal ratio; and cup to disc vertical ratio) generated by backward elimination method was 0.929. CONCLUSIONS: The performance of individual parameters obtained from Stratus OCT is fairly reliable for differentiating the early glaucomatous eyes from normal eyes. However, the discriminant power increases when LDA with forward selection and backward elimination methods is applied.

Adult↗
PubMed2005

Relation between intraocular pressure and systemic health parameters in Taiwan.

OBJECTIVE: The aim of the study was to evaluate the association between intraocular pressure (IOP) and several systemic health parameters in Taiwan. METHODS: We retrospectively reviewed the medical records from all participants who had been examined in China Medical University Hospital. A total of 1,271 subjects (mean age, 50.0 +/- 12.0 years; age range, 21 to 85) who had not undergone any medical treatment for ocular hypertension or glaucoma were included in this study. Systemic factors (age, sex, blood pressure, total cholesterol, triglycerides, fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index, waist circumference) were measured. One-way analysis of variance, Pearson correlation coefficients, and multivariate linear regression were used. RESULTS: There were 674 (53.0%) males and 597 (47.0%) females in this study. After controlling for the other covariates, the multivariate linear regression analysis showed that in males and females, systolic blood pressure was positively associated with IOP. That is, a change in systolic blood pressure by 1 mm Hg would alter the measured IOP by 0.024 mm Hg in males (95% CI, 0.002, 0.046; P = 0.031) and 0.030 mm Hg in females (95% CI, 0.006, 0.053; P = 0.014). In males, age was inversely associated with IOP. That is, a change in age by 1 year would alter the measured IOP by -0.039 mm Hg (95% CI, -0.059, -0.020; P = 0.0001). CONCLUSIONS: IOP was found to have a strong positive association with systolic blood pressure in males and females. IOP was inversely associated with age in males. This study may provide basic information for further studies on IOP in Taiwan.

Adult↗
PubMed2005

Development and comparison of automated classifiers for glaucoma diagnosis using Stratus optical coherence tomography.

PURPOSE: To develop and compare the ability of several automated classifiers to differentiate between normal and glaucomatous eyes based on the quantitative assessment of summary data reports from Stratus optical coherence tomography (OCT; Carl Zeiss Meditec Inc., Dublin, CA) in a Chinese population in Taiwan. METHODS: One randomly selected eye from each of 89 patients with glaucoma and each of 100 age- and sex-matched normal individuals were included in the study. Measurements of glaucoma variables (retinal nerve fiber layer thickness and optic nerve head analysis results) were obtained by Stratus OCT. With the Stratus OCT parameters used as input, receiver operative characteristic (ROC) curves were generated by three methods, to classify eyes as either glaucomatous or normal: linear discriminant analysis (LDA), Mahalanobis distance (MD), and artificial neural network (ANN). The area under the ROC curve was optimized by principal component analysis (PCA). Classification accuracy was determined by cross validation. RESULTS: The average visual field mean deviation was -0.7 +/- 0.6 dB in the normal group and -2.7 +/- 1.9 dB in the glaucoma group. The areas under the ROC curves were 0.824 (LDA), 0.849 (MD), 0.821 (ANN), 0.915 (LDA with PCA), 0.991 (MD with PCA), and 0.874 (ANN with PCA). CONCLUSIONS: With Stratus OCT parameters used as input, automated classifiers show promise for discriminating between glaucomatous and normal eyes. MD measured from multivariate data can predict the severity of glaucoma through the construction of a measurement space. After PCA, implementation results show that the Mahalanobis space created by MD surpasses LDA and ANN in diagnosing glaucoma.

Adult↗
PubMed2005

Retinal nerve fiber layer thickness measured by optical coherence tomography and its correlation with visual field defects in early glaucoma.

BACKGROUND AND PURPOSE: To study the relationship between retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and visual field defects in early glaucomatous eyes and to study the diagnostic ability of OCT in distinguishing early glaucomatous eyes from normal eyes. METHODS: We studied 68 eyes from primary open-angle glaucoma patients with early visual field defect (mean deviation > -6 dB), and 94 normal eyes from healthy age- and gender- matched individuals. All participants underwent 3.4-mm diameter circular OCT scans and Humphrey 30-2 mode visual field testing. The average and segmental RNFL thickness values were compared between the 2 groups. The correlation between the mean deviation in the visual field examination and RNFL thickness was evaluated. The area under the receiver operating characteristic (ROC) curve was used to distinguish normal eyes from early glaucomatous eyes. RESULTS: There was a significant difference in RNFL thickness between the 2 groups based on the following parameters: average thickness; superior, inferior, and nasal quadrant thickness; and 1-7, 11, 12 o'clock hour segment thickness (p < 0.05). In the glaucoma group, superior and inferior quadrant thicknesses and average RNFL thickness significantly correlated with the visual field index (superior quadrant thickness, r = 0.36; inferior quadrant thickness, r = 0.32; average RNLF thickness, r = 0.35; p < 0.05). The average RNFL and inferior quadrant thickness of early glaucomatous eyes had the widest areas under the ROC curves (0.812 and 0.793, respectively). CONCLUSIONS: Measurement of average and inferior quadrant RNFL thickness by OCT is useful in detecting early glaucomatous change.

Adult↗
PubMed2004

Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.

Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy.

Animals↗
PubMed2003

Relationship between retinal vein occlusion and axial length.

This study examined whether axial length is a local risk factor for central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The study group consisted of 40 patients with unilateral CRVO and 77 patients with unilateral BRVO. The control group included 67 individuals who matched the study group patients in age, systemic hypertension, and diabetes mellitus status. The axial lengths of affected and fellow eyes of patients and controls were measured using A-scan ultrasonography. The axial length of affected eyes was statistically significantly shorter than that of unaffected eyes in the BRVO group (p < 0.05) but not in the CRVO group (p = 0.05). There were also statistically significant differences in axial length between control eyes and affected eyes in both the CRVO group (p < 0.05) and BRVO group (p < 0.05). Thus, shorter axial length could be a risk factor for developing CRVO and BRVO. The axial lengths of affected eyes in retinal vein occlusion patients tend to be shorter than those of unaffected eyes, especially in BRVO patients.

Eye↗
PubMed2003

Intravitreous recombinant tissue plasminogen activator and gas to treat submacular hemorrhage in age-related macular degeneration.

We evaluated the safety and efficacy of intravitreous recombinant tissue plasminogen activator (rTPA) and gas for the treatment of submacular hemorrhage in age-related macular degeneration (ARMD). From January 2000 to April 2002, we enrolled 15 patients with submacular hemorrhage secondary to ARMD. All patients received 100 microg rTPA and 0.3 mL perfluoropropane intravitreously. Postoperatively, all patients were kept in a supine position for 4 hours followed by a face-down position for 4 days. Anatomic and functional results were evaluated during a follow-up period of 6 to 19 months. Submacular blood was completely displaced in 12 patients (80%) and partially in three (20%). Best postoperative visual acuity improved in all 15 eyes; in seven eyes (47%), the improvement was two or more lines. Final visual acuity improved in 12 eyes, remained stable in two eyes, and worsened in one eye. Onset of hemorrhage within 21 days was associated with better gains of lines in best postoperative (p = 0.0256) and final visual acuity (p = 0.044). Although two patients developed mild breakthrough vitreous hemorrhage within 1 day after treatment, no rTPA-related retinal toxicity was observed. Intravitreous injections of rTPA and gas are safe and effective in improving visual acuity in patients with submacular hemorrhage secondary to ARMD. Although the final visual outcome is often limited by the progression of the disease, significant and stable visual recovery over an extended follow-up period is possible using this easy and convenient technique.

Aged↗