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PubMed | Tri Service General Hospital, China Medical University at Taichung, Bharathyiar University, Chia Nan University of Pharmacy and Science and 4 more.
Type: Journal Article | Journal: The Chinese journal of physiology | Year: 2016

Peripheral nerve injuries, caused by accidental trauma, acute compression or surgery, often result in temporary or life-long neuronal dysfunctions and inflict great economic or social burdens on the patients. Nerve cell proliferation is an essential process to restore injured nerves of adults. Schwann cells play a crucial role in endogenous repair of peripheral nerves due to their ability to proliferate, migrate and provide trophic support to axons via expression of various neurotrophic factors, such as the nerve growth factor (NGF), especially after nerve injury. Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid, isolated from the kernels of Alpinia oxyphylla Miq (AOF), a traditional Chinese herbal medicine the fruits of which are widely used as a tonic, aphrodisiac, anti-salivation and anti-diarrheatic. This study investigated the molecular mechanisms by which PCA induces Schwann cell proliferation by activating IGF-IR-PI3K-Akt pathway. Treatment with PCA induces phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3 kinase/serine - threonine kinase (PI3K/Akt) pathway, and activates expression of cell nuclear antigen (PCNA) in a dose-dependent manner. Cell cycle analysis after 18 h of treatment showed that proliferation of the RSC96 cells was enhanced by PCA treatment. The PCA induced proliferation was accompanied by modulation in the expressions of cell cycle proteins cyclin D1, cyclin E and cyclin A. Knockdown of PI3K using small interfering RNA (siRNA) and inhibition of IGF-IR receptor resulted in the reduction in cell survival proteins. The results collectively showed that PCA treatment promoted cell proliferation and cell survival via IGF-I signaling.


PubMed | Changhua Christian Hospital, Bharathiar University, China Medical University at Taichung, Meiho University and 2 more.
Type: | Journal: Evidence-based complementary and alternative medicine : eCAM | Year: 2015

Partial hepatectomy (PHx) is a liver regeneration physiological response induced to maintain homeostasis. Liver regeneration evolved presumably to protect wild animals from catastrophic liver loss caused by toxins or tissue injury. Silymarin (Sm) ability to stimulate liver regeneration has been an object of curiosity for many years. Silymarin has been investigated for use as an antioxidant and anticarcinogen. However, its use as a supportive treatment for liver damage is elusive. In this study, we fed silymarin (Sm, 25mg/kg) to male Sprague-Dawley rats for 7 weeks. Surgical 2/3 PHx was then conducted on the rats at 6hrs, 24hrs, and 72hrs. Western blot and RT-PCR were conducted to detect the cell cycle activities and silymarin effects on hepatic regeneration. The results showed that silymarin enhanced liver regeneration by accelerating the cell cycle in PHx liver. Silymarin led to increased G1 phase (cyclin D1/pRb), S phase (cyclin E/E2F), G2 phase (cyclin B), and M phase (cyclin A) protein and mRNA at 6hrs, 24hrs, and 72hrs PHx. HGF, TGF, and TGF1 growth factor expressions were also enhanced. We suggest that silymarin plays a crucial role in accelerated liver regeneration after PHx.


Lin P.-P.,China Medical University at Taichung | Lin P.-P.,Asia University, Taiwan | Lin P.-P.,Hungkuang University | Hsieh Y.-M.,Providence University | And 10 more authors.
International Journal of Molecular Medicine | Year: 2013

Apoptosis is recognized as a predictor of adverse outcomes in subjects with cardiac diseases. The aim of this study was to explore the effects of probiotic-fermented purple sweet potato yogurt (PSPY) with high γ-aminobutyric acid (GABA) content on cardiac apoptosis in spontaneously hypertensive rat (SHR) hearts. The rats were orally adminsitered with 2 different concentrations of PSPY (10 and 100%) or captopril, 15.6 mg/kg, body weight (BW)/day. The control group was administered distilled water. DAPI and TUNEL staining were used to detect the numbers of apoptotic cells. A decrease in the number of TUNEL-positive cardiac myocytes was observed in the SHR-PSPY (10 and 100%) groups. In addition, the levels of key components of the Fas receptor- and mitochondrial-dependent apoptotic pathways were determined by western blot analysis. The results revealed that the levels of the key components of the Fas receptor- and mitochondrial-dependent apoptotic pathway were significantly decreased in the SHR-captopril, and 10 and 100% PSPY groups. Additionally, the levels of phosphorylated insulin-like growth factor I receptor (p-IGF-IR) were increased in SHR hearts from the SHR-control group; however, no recovery in the levels of downstream signaling components was observed. In addition, the levels of components of the compensatory IGF-IR-dependent survival pathway (p-PI3K and p-Akt) were all highly enhanced in the left ventricles in the hearts form the SHR-10 and 100% PSPY groups. Therefore, the oral administration of PSPY may attenuate cardiomyocyte apoptosis in SHR hearts by activating IGF-IR-dependent survival signaling pathways.


Lin K.-H.,China Medical University at Taichung | Kuo C.-H.,University of Taipei | Kuo W.-W.,China Medical University at Taichung | Ho T.-J.,China Medical University at Taichung | And 8 more authors.
Journal of Cellular Biochemistry | Year: 2015

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF2R) over-expression correlates with heart disease progression. The IGF2R is not only an IGF2 clearance receptor, but it also triggers signal transduction, resulting in cardiac hypertrophy, apoptosis and fibrosis. The present study investigated the nuclear factor IL-3 (NFIL3), a transcription factor of the basic leucine zipper superfamily, and its potential pro-survival effects in cardiomyocytes. NFIL3 might play a key role in heart development and act as a survival factor in the heart, but the regulatory mechanisms are still unclear. IGF2 and IGF2R protein expression were highly increased in rat hearts subjected to hemorrhagic shock. IGF2R protein expression was also up-regulated in H9c2 cells exposed to hypoxia. Over-expression of NFIL3 in H9c2 cardiomyoblast cells inhibited the induction of hypoxia-induced apoptosis and down-regulated IGF2R expression levels. Gel shift assay, double-stranded DNA pull-down assay and chromatin immune-precipitation analyses indicated that NFIL3 binds directly to the IGF2R promoter region. Using a luciferase assay, we further observed NFIL3 repress IGF2R gene promoter activity. Our results demonstrate that NFIL3 is an important negative transcription factor, which through binding to the promoter of IGF2R, suppresses the apoptosis induced by IGF2R signaling in H9c2 cardiomyoblast cells under hypoxic conditions. J. Cell. Biochem. 116: 1113-1120, 2015. © 2015 Wiley Periodicals, Inc.


Huang C.-Y.,China Medical University at Taichung | Huang C.-Y.,Asia University, Taiwan | Kuo W.-W.,China Medical University at Taichung | Shibu M.A.,China Medical University at Taichung | And 8 more authors.
American Journal of Chinese Medicine | Year: 2014

Factors that enhance the intrinsic growth potential of neurons play a major role in the regeneration and repair of adult neurons following an injury. Fibroblast growth factor (FGF-2) is one of the key players in the origin and growth of neuronal and glial cells through autocrine and paracrine signaling. Water extract of Citrus medica var. sarcodactylis (fingered citron, foshou), which is been used effectively as a Chinese herbal medicine, was found to activate the FGF-2 promoter in transgenic luciferase expression models. Foshou treatment on Schwann cells (RSC96) transfected with luciferase reporter plasmid under a FGF-2 promoter was found to induce the FGF-2 promoter and showed enhanced luciferase expression. The FGF-2 expression was accompanied with an increase in the expression of proteins involved in cell migration and cell proliferation in a dose dependent manner. Therefore, foshou potentially enhances nerve regeneration by inducing the Schwann cell proliferation and migration. © 2014 World Scientific Publishing Company.


Lin C.-C.,National Chung Hsing University | Lin C.-C.,Armed Forces General Hospital | Chao P.-Y.,National Chin - Yi University of Technology | Chao P.-Y.,China Medical University at Taichung | And 6 more authors.
American Journal of Chinese Medicine | Year: 2014

Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will metastasize to the lungs or liver, and as a result, patients generally need chemotherapy to improve survival possibility. Recently, antitumor activity has been reported in Ocimum gratissimum aqueous extract (OGE), which has been the focus of recent extensive studies on therapeutic strategies due to its antioxidant properties. We performed pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth. Cell viability, Western blot and flow cytometry analysis were performed before performing pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth, including cDNA microarray and RT-PCR assays. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of U2-OS and HOS cells. Increases in cell shrinkage, Sub-G1 fragments and the activation of caspase 3 indicated that OGE induced cell apoptosis in U2-OS and HOS cells. There was no change in human osteoblast hFOS cells. cDNA microarray assay demonstrated that the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers were all modified by OGE treatment. RT-PCR analysis also confirmed the down-regulation of SKA2 and BUB1B, and the up-regulation of PPP1R15A, SQSTM1, HSPA1B, and DDIT4 by OGE treatment. The finding of anticancer activity in OGE and the identification of some potential target genes raise the expectation that OGE may become a useful therapeutic drug for human OS. © 2014 World Scientific Publishing Company.


PubMed | University of Science and Technology of China, Bharathiar University, China Medical University at Taichung, Chung Shan Medical University and 4 more.
Type: Journal Article | Journal: International journal of medical sciences | Year: 2015

Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance.Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot.Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure.Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke.


Lin P.-P.,Providence University | Hsieh Y.-M.,Providence University | Kuo W.-W.,University of Science and Technology of China | Lin C.-C.,Armed Forces General Hospital | And 7 more authors.
International Journal of Molecular Medicine | Year: 2012

Cardiovascular hypertrophy is a common feature of hypertension and an important risk factor for heart damage. The regression of cardiovascular hypertrophy is currently considered an important therapeutic target in reducing the omplications of hypertension. The aim of this study was to investigate the inhibition of cardiac hypertrophy by probiotic-fermented purple sweet potato yogurt (PSPY) with high ã-aminobutyric acid (GABA) content in spontaneously hypertensive rat (SHR) hearts. Six-week-old male SHRs were separated randomly and equally into 4 experimental groups: sterile water, captopril and 2 PSPY groups with different doses (10 and 100%) for 8 weeks. The changes in myocardial architecture and key molecules of the hypertrophy-related pathway in the excised left ventricle from these rats were determined by histopathological analysis, hematoxylin and eosin staining and western blot analysis. Abnormal myocardial architecture and enlarged interstitial spaces observed in the SHRs were significantly decreased in the captopril and PSPY groups compared with the sterile water group. Moreover, the increases in atrial natriuretic peptide, B-type natriuretic peptide, phosphorilated protein kinase Cα and calmodulin-dependent protein kinase II levels in the left ventricle were accompanied by hypertension and increases in phosphorylated extracellular signal-regulated kinase 5 activities with enhanced cardiac hypertrophy. However, the protein levels of the hypertrophic-related pathways were completely reversed by the administration of PSPY. PSPY may repress the activation of ANP and BNP which subsequently inhibit the dephosphorylation of the nuclear factor of activated T-cells, cytoplasmic 3 and ultimately prevent the progression of cardiac hypertrophy.


PubMed | Changhua Christian Hospital, China Medical University at Taichung, Chung Shan Medical University, University of Science and Technology of China and 3 more.
Type: Journal Article | Journal: The Chinese journal of physiology | Year: 2016

The aim of this study was to establish the effective hepatoprotective properties of traditional Chinese medicines (TCMs) in fibrotic rat liver regeneration after partial hepatectomy (PHx). Fibrosis was induced in rats by ethanol (EtOH, 5 ml/kg) administration for 6, 24, 72, and 168 h. The rats were then fed four TCMs (1 g/kg/day, Codonopsis pilosula (CP), Salvia miltorrhiza Bunge (SMB), Bupleurum kasi (BK), and Elephantopus scaber L (ESL)) to Spraque-Dawley rats for 6, 24, 72 and 168 h, respectively. Surgical 70% cirrhotic fibrosis PHx was then conducted at 6, 24, 72, and 168 h. The effects on liver regeneration were examined to estimate and measure hepatocyte growth factor (HGF), focal adhesion kinase (FAK), Cyclin D1, Cyclin E, and retinoblastoma protein (pRb) protein expression using Western blotting analysis. Cyclin D1, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and TIMP-3 mRNA by Reverse transcription polymerase chain reaction (RT-PCR) were analyzed in cirrhotic fibrosis rats. Transforming growth factor-1 (TGF-1), Cyclin D1, Cyclin E, pRb and E2F mRNA expression levels were determined in fibrotic rats following PHx using RT-PCR. We found elevated glutamyl oxaloacetic transaminase (GOT), glutamyl pyrubic transaminase (GPT), alkaline phosphatase (ALP), gammaglutamyl transpeptidase (-GT), glutathione (GSH), nonprotein sulfhydryl (NPSH) and total bilirubin in serum after 6 h EtOH administration. These levels were progressively decreased over 168 h. Total protein and albumin were reduced in serum after 6 h administration and then progressively increased. In contrast, tissues disorder histology and morphology were determined in liver sections. After rats were fed TCMs we found that SMB extraction not only induced HGF, FAK, Cyclin D1, and pRb protein expression and Cyclin D1 mRNA increases, but also reduced MMP-2 and MMP-9 after 24 and 72 h post injury. In the cell cycle S phase the Cyclin E protein expression was increased by ESL. CP induced TIMP-1, TIMP-2 and TIMP-3 mRNA increases in fibrotic rats. We detected liver regeneration in fibrotic rats. We also found that the liver regeneration index increased from 6 to 168 h post PHx. After 168 h fibrotic liver regeneration rats exhibited reduced TGF-1 mRNA expression and enhanced Cyclin D1, Cyclin E, pRb and E2F mRNA expression. TCMs play a crucial role in the early mediating process in fibrotic rat liver regeneration after PHx.


Pan C.-W.,Armed Forces General Hospital | Tsao M.-J.,Armed Forces General Hospital | Su M.-S.,Armed Forces General Hospital
BMJ Case Reports | Year: 2015

De Garengeot hernia is a rare clinical entity defined as the presence of a vermiform appendix within a femoral hernia sac. A 50-year-old woman presented to the emergency department with a painful lump over her right groin region. A bedside ultrasound was performed and soft tissue lesion was suspected. CT was performed and revealed a swollen tubular structure with fat stranding within the mass. De Garengeot hernia with acute appendicitis was diagnosed preoperatively, and an emergency appendectomy and hernioplasty were performed. Although it is usually an incidental finding during hernioplasty, De Garengeot hernia should be considered in the differential diagnosis of patients with an incarcerated femoral hernia. Mesh repair can be performed depending on the clinical situation. We report a rare case of incarcerated femoral hernia with acute appendicitis that required early surgical management to avoid associated complications.

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