The present study aimed to investigate the hepatoprotective effect of resveratrol (RSV) against ethanol-induced oxidative stress in vivo, and investigate the underlying mechanisms by which RSV exerts ...its anti-oxidative effects on hepatic cells. C57BL/6J mice were divided into four groups: Untreated control, ethanol-treated, RSV-treated, and ethanol + RSV-treated. The plasma lipid profile, hepatic lipid accumulation and antioxidative enzyme activities were analyzed. HepG2 cells were used as a cellular model to analyze the effects of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxisome proliferator-activated receptors (PPARs) in the RSV-mediated protection of ethanol-induced oxidative stress. In C57BL/6J mice, ethanol caused a significant increase in plasma triglyceride levels and hepatic lipid accumulation (P<0.05), whereas RSV notably increased SOD activity. In HepG2 cells, SOD activity was enhanced in the RSV-treated HepG2 cells, whereas the activity of CAT and GPx was not affected. Western blot and quantitative polymerase chain reaction analyses demonstrated that RSV significantly increased SOD protein and mRNA expression levels (P<0.05). Using a transient transfection assay, PPARγ was observed to participate in the regulation of SOD gene expression in RSV-administered HepG2 cells. To conclude, the results from the present study suggest that RSV may contribute towards the protection of hepatic cells from ethanol-induced oxidative stress via the induction of SOD activity and gene expression.
The CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) and CXC receptor 4 (CXCR4) axis is involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression ...of CRC. Interaction between CRC cells and endothelium is a key event in tumor progression. The aim of this study was to investigate the effect of SDF-1 on the adhesion of CRC cells.
Human CRC DLD-1 cells were used to study the effect of SDF-1 on intercellular adhesion molecule-1 (ICAM-1) expression and cell adhesion to endothelium.
SDF-1 treatment induced adhesion of DLD-1 cells to the endothelium and increased the expression level of the ICAM-1. Inhibition of ICAM-1 by small interfering RNA (siRNA) and neutralizing antibody inhibited SDF-1-induced cell adhesion. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK, JNK and p38 pathways is critical for SDF-1-induced ICAM-1 expression and cell adhesion. Promoter activity and transcription factor ELISA assays showed that SDF-1 increased Sp1-, C/EBP-β- and NF-κB-DNA binding activities in DLD-1 cells. Inhibition of Sp1, C/EBP-β and NF-κB activations by specific siRNA blocked the SDF-1-induced ICAM-1 promoter activity and expression. The effect of SDF-1 on cell adhesion was mediated by the CXCR4.
Our findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.
Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors ...metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.
Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity.
Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.
In traditional Chinese culture, liver disease is believed to underlie excessive daytime sleepiness (EDS). Consequently, Chinese patients with complaints of EDS and physicians who treat them suspect ...that a liver abnormality is present. If liver disease is ruled out, these patients are often discharged without treatment. Gastroesophageal reflux disease (GERD) is a common disorder also associated with EDS. This pilot study was undertaken to determine the prevalence of GERD among Taiwanese patients with complaints of EDS suspected to be related to liver disease but in whom no evidence for the latter was found.
From July 2009 to December 2009, 121 outpatients who presented to or were referred to the Department of Gastroenterology and Hepatology of the Chiayi Gung Memorial Hospital for evaluation of a complaint of EDS thought to be due to liver disease were examined. Demographic data were collected, and physical examinations and liver function tests were performed. Forty-eight patients had liver disease and were excluded. The Chinese Epworth Sleepiness Scale questionnaire (Chinese ESS) and the Chinese Gastroesophageal Reflux Disease Questionnaire (CGERDQ) were then administered to 73 included patients.
More than half (56.2%) of the included patients were found to suffer from GERD. Patients with symptoms of GERD had higher mean CGERDQ scores than patients without symptoms of the disorder (18.88 ± 5.49 and 5.56 ± 3.57, respectively; P < 0.001). Patients with symptoms of GERD also had higher mean Chinese ESS scores than patients without symptoms (8.80 ± 5.49 and 3.13 ± 3.50, respectively; P < 0.001). Chinese ESS scores indicative of EDS were observed in 48.8% of patients with symptoms of GERD and in 3.1% of those without symptoms (P < 0.001). Differences between the two groups retained their significance after controlling for potential confounders.
A significant percentage of Taiwanese patients who complained of EDS and were admitted to our Hepatology/Gastroenterology Department due to a suspicion of liver disease actually had symptoms of GERD. Further studies are needed to ascertain whether treatment of GERD will effectively resolve EDS in these patients.
Abstract
Direct‐acting antivirals (DAAs) have become an effective first‐line treatment for chronic hepatitis C (CHC), and the fixed‐dose combination of sofosbuvir (SOF) and velpatasvir (VEL) is one ...of the most important pangenotypic DAA regimen according to present treatment guideline. The association between SOF‐based regimens and renal toxicity remains controversial. A total of 953 patients including 130 with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m
2
and 823 with eGFR > 60 mL/min/1.73m
2
receiving SOF/VEL therapy for 12 weeks were enrolled in this study. The eGFR was assessed at baseline, end of treatment (EOT), and 12 weeks after completion of the therapy (end of follow‐up, EOF). The eGFR in patients with eGFR ≤ 60 mL/min/1.73m
2
increased from baseline (47.89 ± 10.25 mL/min/1.73m
2
) to EOT (51.65 ± 15.92;
P
< .001) and EOF (51.51 ± 14.46 mL/min/1.73m
2
;
P
< .05). The eGFR in patients with eGFR > 60 mL/min/1.73m
2
at baseline (91.52 ± 22.06 mL/min/1.73m
2
) was lower at EOT (90.37 ± 22.3;
P
< .05), with no difference between EOT and EOF (
P
= .06). Multivariable analysis showed that a higher serum albumin level was associated with a lower risk of eGFR decrease at EOT, and the patients with baseline eGFR > 60 mL/min/1.73m
2
were associated with a higher risk of eGFR decrease at EOF. The rates of sustained virologic response 12 weeks after treatment cessation (SVR12) were 99.2% in per‐protocol analysis, and the most common adverse events were fatigue (4.7%), abdominal discomfort (4.5%), and skin itching (3.7%). In conclusion, renal function improved after the SOF/VEL treatment in patients with CHC and chronic kidney disease. Thus, SOF/VEL was safe, effective, and tolerable in these patients.
Summary
Background
Limited data are available on the interval of disease‐free status after endoscopic submucosal dissection (ESD) for early gastric cancer and precancer lesion in Taiwan. In this ...long‐term (2–105 months) follow‐up study, we analyzed the risk factors that affect the local recurrence and noncurative resection (non‐CR) of these lesions.
Methods
We retrospectively studied 65 consecutive treatment‐naïve patients with 69 EGC lesions who were selected to be treated by ESD. A total of 56 lesions (48 CR lesions and 8 non‐CR lesions) were analyzed for local recurrence after ESD.
Results and Discussion
ESD was curative for gastric epithelial tumors in 51 (73.9%) but not in 18 (26.1%) lesions. Unfortunately, five (8.93%) of these 56 lesions in 53 patients had local recurrence. None of the patients died from gastric cancer‐associated diseases during follow‐up. In our studies, the cumulative local recurrence rates were 5.3% in the CR group and 56.7% in the non‐CR group (p = 0.0091). The disease‐free status was high (94.7%) with CR. The risk factors that affect the non‐CR were tumor location (p = 0.013), deeper invasion (p < 0.001), undifferentiated histopathology (p < 0.001), and ulcer presence (p = 0.045).
Conclusion
ESD offers good outcome after treatment for EGC. To decrease the risk of local recurrence, preoperative diagnosis of tumor extent and accurate postoperative pathological evaluation are very important.
碩士
國立臺灣海洋大學
電機工程學系
106
The power produced by renewable energy generators is not steady as traditional generators and we can predict that will impact on the isolated power system of Taiwan after ...integrating large-scale wind energy into the power grid. However, as the energy structure of our country changes, it should be considered that the possible influence of renewable energy before planning the frequency regulation capacity. Consequently , how to plan frequency regulation requirements for wind farm balancing both the quality and the cost of power system, this point is worth a discussion among us. For avoiding this situation, the purpose of this thesis is to plan the suitable frequency regulation requirements for Wind Turbines.
The thesis found the relationships between variables in the time domain by referring to the DFIG wind turbine control model (WT3) built in PSS/E. Also, according to historical data of Guanyuan Wind Farm consolidation, we defined the efficiency of each wind turbine generator between di
Hericium erinaceus, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, ...and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of H. erinaceus mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing H. erinaceus mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of H. erinaceus mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with H. erinaceus mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of H. erinaceus mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.
PDF
