PubMed Health⌕ Search

Biomedical subjects

Hsin-Hung Chen

Publications and source records attributed to Hsin-Hung Chen.

15 recordsLinked to original sources
PubMed2026

High-fat diet-responsive DNM1 promotes hepatocellular carcinoma progression and predicts poor prognosis in viral-associated patients.

Hepatocellular carcinoma (HCC) arises from diverse etiologies, among which metabolic dysfunction-associated liver disease and chronic viral hepatitis are the two major drivers worldwide. However, the molecular mechanisms linking metabolic stress to HCC progression remain incompletely understood. Dynamin-1 (DNM1), primarily known for its role in vesicular trafficking, has emerged as a potential oncogene, yet its prognostic and functional significance in HCC remains largely unexplored. Here, we investigated the role of DNM1 in high-fat diet (HFD)-associated hepatocarcinogenesis. Transcriptomic profiling was conducted to identify differentially expressed genes between normal and high-fat diet murine models, with human orthologs mapped. Clinical relevance was validated using The Cancer Genome Atlas (TCGA-LIHC) dataset. Survival analysis, GSEA (Gene Set Enrichment Analysis), and subgroup stratifications based on viral hepatitis status were performed. In vitro, loss-of-function assays (shRNA knockdown) were executed in HepG2 and SK-Hep1 cell lines to assess cell viability and migration. DNM1 was significantly upregulated in high-fat diet models. In the TCGA-LIHC cohort, high DNM1 expression was an independent risk factor for poor overall survival (HR=1.44, P=0.039) and correlated with advanced tumor stages (Stage III+IV, P=0.010). In vitro knockdown of DNM1 profoundly impaired cell proliferation and migration in HCC cell lines. Strikingly, DNM1 expression was further elevated in patients with concurrent viral hepatitis (P=0.009). GSEA revealed that high DNM1 expression was positively associated with viral infection pathways and negatively correlated with critical immune responses, including interferon-alpha/gamma responses and host immune cytolysis. Survival analysis stratified by four subgroups demonstrated that patients with both viral infection and high DNM1 expression exhibited the worst prognosis (Overall Log-rank P < 0.001). Our findings identify DNM1 as a high-fat diet-responsive regulator that links metabolic stress to hepatocellular carcinoma progression. Elevated DNM1 expression promotes malignant phenotypes in HCC and identifies a subgroup of viral-associated patients with particularly poor prognosis, highlighting DNM1 as a potential prognostic biomarker and therapeutic target.

Hepatocellular carcinoma (HCC)↗
PubMed2006

1,1,1-tris(hydroxymethyl)ethane as a new, efficient, and versatile tripod ligand for copper-catalyzed cross-coupling reactions of aryl iodides with amides, thiols, and phenols.

1,1,1-tris(hydroxymethyl)ethane was presented as a new, efficient, and versatile tridentate O-donor ligand suitable for the copper-catalyzed formation of C-N, C-S, and C-O bonds. This inexpensive and commercially available tripod ligand has been demonstrated to facilitate the copper-catalyzed cross-coupling reactions of aryl iodides with amides, thiols, and phenols to afford the corresponding desired products in good to excellent yields. [reaction: see text].

Alkanes↗
PubMed2006

Pro-apoptotic low-density lipoprotein subfractions in type II diabetes.

OBJECTIVE: To test the hypothesis that differences in subfractions of circulating lipoproteins between diabetic and non-diabetic subjects exist and might contribute to the increased risk for atherosclerosis in type II diabetics. METHODS AND RESULTS: LDL isolated from diabetic (D) and control subjects (N) were separated by FPLC into five subfractions (L1-L5). The fractional distributions of N- and D-LDL were not different, but the most strongly retained subfractions of D-LDL (D-L5) were markedly more pro-apoptotic to bovine aortic endothelial cells in vitro than were the other subfractions in D- or N-LDL. D-L5 induced time- and concentration-dependent apoptosis that was inhibited by z-VAD-fmk. The most electronegative D-LDL subfractions contained substantial amounts of apoproteins AI, E and CIII, higher concentrations of non-esterified fatty acids and LpPLA2, and lower trinitrobenzenesulfonic acid (TNBSA) reactivities. Electronegative subfractions of D-LDL exhibited longer lag times and lower net increases in absorbance at 234 nm with Cu-catalyzed oxidation in vitro. CONCLUSIONS: The toxicities of electronegative subfractions of LDL from diabetic subjects to endothelial cells in vitro may be pivotal to vascular complications of diabetes in vivo, but the specific molecular alterations responsible for the toxicities of these subfractions of diabetic LDL are not known.

Aged↗
PubMed2006

L5, the most electronegative subfraction of plasma LDL, induces endothelial vascular cell adhesion molecule 1 and CXC chemokines, which mediate mononuclear leukocyte adhesion.

We have previously reported that L5, the most negatively charged subfraction of plasma low-density lipoprotein (LDL), induces mononuclear leukocyte (MNC) adhesion under flow conditions in vitro when endothelial cells are incubated with L5. The present study was undertaken to identify responsible adhesion molecules and chemokines. LDL isolated from patients with homozygous familial hypercholesterolemia was separated into five distinct subfractions by high-capacity ion-exchange chromatography. Differentially expressed mRNA between human umbilical vein endothelial cells (HUVEC) incubated (for 22h) with the earliest subfraction (L1: 20 microg/ml) and the latest and most negatively charged subfraction (L5: 20 microg/ml) was identified by DNA microarray analysis using three independent sets of RNA. mRNA consistently upregulated by L5 included VCAM-1 (2.3-fold) and CXC chemokines GRO-alpha (2.3), GRO-beta (4.6), IL-8 (2.5), ENA-78 (2.3), GRO-gamma (1.6) and GCP-2 (1.5). These results were validated by Northern analysis, semi-quantitative RT-PCR or ELISA. Blocking studies using monoclonal antibodies revealed that both primary capture and stable adhesion of MNC to HUVEC and human aortic endothelial cells (HAEC) incubated with L5 was mediated by VCAM-l/alpha4 integrin, whereas GRO and its receptor CXCR2 were involved in the stable adhesion of MNC to L5-treated HAEC.

Aorta↗
PubMed2006

Inconspicuous visual field defect in anterior choroidal artery territory infarction.

We describe a patient with a right anterior choroidal artery territory infarction and an inconspicuous left visual defect. The anterior choroidal artery is a unique artery of the cerebral circulation. The occlusion of this artery can result in dysfunction of motor, sensory, and visual systems with only rare involvement of higher cortical function. Among symptoms reported, visual abnormalities are the most variable and the least common. However, the visual field abnormality may be overlooked and the incidence underestimated since some patients may not be aware of the problem until uncovered by formal visual field testing.

Aged↗
PubMed2006

A simple and economical method for the manual construction of well-aligned tissue arrays.

Tissue array technology has allowed a substantial progression of studies correlating molecular and immunohistochemical findings with clinico-pathological information. Array construction presents technical difficulties and tissue arrayers are expensive, particularly for small and medium sized laboratories. We describe a simple manual method for producing well-aligned tissue arrays using a hand-made paper mold which can successfully perform immunohistochemical staining. All 200 tissue samples were collected and constructed into blocks by the paper mold. The tissue arrays were smoothly sectioned using a standard microtome and performed for a panel of immunohistochemical study with satisfactory results. This alterative method for building custom arrays could be applied in any laboratory and is both simple and economical.

Humans↗
PubMed2006

Primary pulmonary synovial sarcoma: a case report.

We report a rare case of primary synovial sarcoma of the lung. A57-year-old man had a well-defined tumor in the right middle lobe seen on chest computed tomography, and underwent lobectomy. Grossly, the nonencapsulated tumor measured 4.5 cm in greatest diameter, with a solid and tan-white cut surface. Histologically, the tumor was mainly composed of a dense proliferation of spindle cells. Immunohistochemical studies were focally positive for epithelial membrane antigen, and diffusely positive for CD99 and Bcl-2. Cytokeratin, S-100 protein, desmin, smooth muscle act in, and CD34 were absent. SYT-SSX1 gene fusion transcript was detected by reverse transcription-polymerase chain reaction, which is diagnostic of primary synovial sarcoma of the lung. We also review the literature with regard to the clinicopathologic, immunohistochemical, and molecular studies of primary pulmonary synovial sarcoma.

Humans↗
PubMed2006

The genetic studies of dementias in Taiwan.

In Taiwan, Alzheimer's disease (AD) followed by vascular dementia (VsD) is the most common cause of dementia among Taiwanese (ethnic Chinese). Several studies have documented the increase of risk for AD among the apolipoprotein E gene allele 4 (ApoE4) carriers in Taiwanese. It is a consensus that ApoE4 is the most important risk factor for AD at present. The researchers also found that ApoE4 allele frequency is lower in Taiwanese, around 7%, than it in the most Caucasian populations. This phenomenon raises the hypothesis that low ApoE4 allele frequency contributes to low prevalence of AD in Taiwanese. Besides, many genetic studies were involved in genetic impacts on modulation or regulation of the manifestation, progression, and treatment response of AD. But, these genetic studies are still inconclusive. Few familial AD attributed to PS1 gene mutation has been identified. The genetic studies of VsD are just beginning and NOTCH3 gene mutation has been detected in Taiwanese cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) families. Since there is a large proportion of non- ApoE4-associated AD in Taiwanese, it remains more researches to look for novel genetic factors in Taiwanese. Based on the Japanese experience of studies, the association between the polymorphisms of ApoE and familial AD, sporadic early-onset AD respectively warrants further investigation.

Alzheimer Disease↗
PubMed2006

Genetic characteristics of dementia in Taiwan.

The most common causes of dementia in Taiwan are Alzheimer's disease (AD) followed by vascular dementia (VaD). Several genetic studies have documented an increased risk of AD among apolipoprotein E gene allele 4 (ApoE4) carriers in Taiwanese (ethnic Chinese). Although ApoE4 is considered the most important risk factor for AD, the ApoE4 allele frequency is lower in Taiwanese (around 7%), than that in most Caucasian populations (over 10%). This phenomenon raises the hypothesis that low ApoE4 allele frequency contributes to the low prevalence of AD in Taiwanese. Other studies of the genetic impacts on modulation or regulation of manifestations, progression, and treatment response of AD in Taiwan have been inconclusive. Familial AD, which is conferred by PS1 gene mutation has been identified. There were very few studies of fronto-temporal dementia (FTD) or dementia with Lewy body (DLB) in Taiwan. Genetic studies of VaD remain limited and only NOTCH3 gene mutation has been detected in a Taiwanese cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) family. Limited data indicated that non- ApoE4-associated AD may represent a larger proportion of AD in Taiwanese, suggesting the existence of novel genetic factors which remain to be identified.

Alzheimer Disease↗
PubMed2005

Modulation of angiogenic processes in cultured endothelial cells by low density lipoproteins subfractions from patients with familial hypercholesterolemia.

OBJECTIVE: Electronegative low density lipoprotein (LDL) subfractions are cytotoxic to endothelial cells. To continue our study of homozygotic familial hypercholesterolemic (FH)-LDL, we report the effects of FH-LDL subfractions (FH-L1 to FH-L5) on the angiogenic processes in cultured endothelial cells. METHODS AND RESULTS: Subconfluent bovine aortic endothelial cells (BAEC) were treated with LDL subfractions (20 microg/ml), and the effects on angiogenic functions, including cell proliferation, migration, apoptosis, tube formation, secretion of matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) were determined. The electronegative FH-L4 and FH-L5 inhibited cell proliferation while the other FH-LDL subfractions and LDL from normocholesterolemic subjects (N-LDL) had negligible effects. Like Cu2+ ox-LDL, FH-L5 strongly inhibited endothelial cell viability and FH-L4 had a milder effects. Similarly, FH-L4 and FH-L5 but not the other subfractions retarded cell migration, induced cell apoptosis, and perturbed tube formation by BAEC in matrigel. FH-L5 inhibited secretion of MMP-2 and MMP-9 by BAEC without affecting their endogenous levels. In contrast, FH-L5 increased the VEGF expression in endothelial cells. CONCLUSIONS: Our results show for the first time that FH-L5, a circulating LDL subfraction from hypercholesterolemic patients, modulates various angiogenic processes, thereby dysregulating endothelial function in a way that may be atherogenic.

Adolescent↗
PubMed2005

Effectiveness of modified constraint-induced movement therapy on upper limb function in stroke subjects.

BACKGROUND AND PURPOSE: Of all stroke survivors, more than 50% are left with motor disabilities. Impairment of upper limb movement is a common motor disability. Constraint-Induced Movement Therapy (CIMT) is an intervention which has been used for the treatment of upper extremity motor disabilities in stroke patients. Although CIMT is an effective intervention, a recent survey revealed that this procedure is viewed with apprehension by many clinicians because of concerns about practicality and resource issues. We developed a modified CIMT that reserves the massed training of the affected arm without any physical restriction of the intact one and then used it on our stroke patients. This study was designed to evaluate the effectiveness of this Modified-Constraint-Induced Movement Therapy (m-CIMT). METHODS: Thirty stroke patients were randomly assigned to either an m-CIMT (n=13) or a control group (n=17). Subjects in the m-CIMT group received a 2-week course of m-CIMT. Outcomes were evaluated using the Wolf Motor Function Test (WMFT). RESULTS: After only 2 weeks of training, significant differences (p<0.05) in favor of m-CIMT were found in the following 6 elements of the WMFT: Extend elbow with weight, Lift pencil, Stack checkers, Flip cards, Turn key in lock, and Lift basket. CONCLUSION: The present study shows that our m-CIMT is useful in improving the function of the affected upper extremity in stroke patients.

Aged↗
PubMed2003

Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins.

OBJECTIVE: Current evidence suggests that oxidatively modified human plasma low-density lipoproteins (ox-LDLs) are proatherogenic and cytotoxic to endothelial and vascular smooth muscle cells. The present study describes a method using ion-exchange chromatography that is capable of large-scale subfractionation of LDL for adequate analyses of composition or bioactivities. METHODS AND RESULTS: LDLs from normolipidemic (N-LDL) and homozygous familial hypercholesterolemic (FH-LDL) subjects were separated into 5 subfractions (L1 through L5) by high-capacity ion-exchange chromatography. The most strongly retained fraction from FH subjects, FH-L5, suppressed DNA synthesis in cultured bovine aortic endothelial cells and stimulated mononuclear cell adhesion to cultured endothelial cells under flow conditions in vitro. L5, which represented 1.1+/-0.2% and 3.7+/-1.7% of the LDL from N-LDL and FH-LDL, respectively, was more triglyceride-rich (17% versus 5%) and cholesteryl ester-poor (23% versus 33%) than were L1 through L4. Electrophoretic mobilities on agarose gels increased from L1 to L5. According to SDS-PAGE, apolipoprotein B-100 in N-LDL fractions L1 through L5 appeared as a single approximately 500-kDa band. In contrast, the fractions isolated from FH-LDL showed substantial fragmentation of the apolipoprotein B-100, including bands between 200 and 116 kDa. Competitive ELISA analyses using a malondialdehyde-specific monoclonal antibody against Cu2+ ox-LDL suggest that FH-L5 is malondialdehyde-modified. CONCLUSIONS: Relative to N-LDL, FH-LDL contains higher concentrations of a fraction, L5, that exhibits distinctive physicochemical properties and biological activities that may contribute to initiation and progression of atherogenesis in vivo.

Adolescent↗
PubMed2003

Metabolic syndrome in obese patients referred for weight reduction surgery in Taiwan.

BACKGROUND AND PURPOSE: The inverse relation between life expectancy and obesity is in large part due to multiple metabolic and cardiovascular comorbidities. Metabolic syndrome (MS) is defined as a cluster of these comorbidities. The prevalence of MS in obesity is not clear. This investigation assessed the prevalence and inter-relationships of MS with various demographic and clinical characteristics in patients with severe obesity. METHODS: A total of 534 obese patients referred to a surgical center for weight reduction surgery were included in this retrospective study. Data collected included blood pressure, anthropometric measurements, and biochemical parameters associated with metabolic comorbidities and MS. The prevalence of MS in various subgroups was analyzed. RESULTS: The frequency of metabolic comorbidities included hypertension in 29.8%, hyperglycemia in 29.0%, hyperlipidemia in 61.0%, hyperuricemia in 57.9%, and abnormal liver function in 60.9%. The presence of any of these 4 metabolic comorbidities in the absence of others was uncommon. Only 28 patients (5.2%) had no metabolic comorbidities. The criteria for MS were met by 217 patients (50.7%). Patients with MS were significantly older (32.9 years vs 29.5 years), more likely to be male (31.9% vs 20.5%) and more likely to have metabolic comorbidities compared with patients without MS. In the multivariate analysis, male gender, age, and abnormal liver function remained significantly associated with the development of MS, while body mass index (BMI) was not. CONCLUSIONS: Metabolic comorbidities were common in the obese patients referred for weight reduction surgery. The cluster of metabolic comorbidities in MS was significantly associated with male gender, and increased age but not with BMI.

Adolescent↗
PubMed2002

Left ventricular inflow propagation velocity: comparisons between pulsed wave and color M-mode Doppler echocardiography.

Sixty-six participants (age 58 +/- 16 years) were included for evaluation of the relationship between color M-mode and pulsed wave Doppler left ventricular inflow propagation velocity (LVIPVcmm and LVIPVpw, respectively). LVIPVpw was measured through the application of the range ambiguity phenomenon, and LVIPVcmm was obtained by manually tracing the first aliasing velocity during the early filling. The variability for LVIPVpw measurements was significantly less than that for LVIPVcmm measurements. There was a significant correlation (r = 0.678, P <.001) between LVIPVcmm and LVIPVpw for all study participants. However, LVIPVpw was greater than LVIPVcmm, especially when the inflow propagation time was relatively short. Age was the only determinant of both LVIPVcmm and LVIPVpw in the control group. As for the patients with diseases retarding inflow propagation, age remained its determinant. However, its impact decreased and the end-systolic dimension and fractional shortening of the left ventricle, instead, turned out to be its major determinant. In conclusion, LVIPVpw measurements are more reproducible than LVIPVcmm measurements. LVIPVpw correlates with LVIPVcmm and their difference significantly correlates with left ventricular inflow propagation time.

Blood Flow Velocity↗