Search

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance.

Although an increasing number of RNA adenosine-to-inosine (A-to-I) editing sites are being discovered, how the editing frequencies of these sites are modulated to fine-tune protein function in adaptive responses is not well understood. A previous study screening for heat tolerance in Drosophila mutants discovered a hypnos-2 mutant strain that was later found to be defective in dADAR, the Drosophila gene encoding the A-to-I editing enzyme. This supports the hypothesis that cells and organisms respond to stressful environments by ADAR (adenosine deaminase acting on RNA)-mediated RNA editing. Here, we investigated changes in the RNA A-to-I editing frequencies of 30 Drosophila nervous system targets in response to heat shock, a stress acclimatization that requires the dADAR function. To our surprise, most of these nervous system editing targets showed reduced editing. Our results suggest that a change in RNA editing pattern is a mechanism by which organisms acclimate to drastic environmental change. However, how RNA editing confers heat resistance is more complicated and requires further investigation.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. It has come to our attention that there is substantial duplication of some figures between this Kaohsiung Journal of Medical Science article and an earlier paper by the same authors, Chao-Neng Tseng et al, A method to identify RNA A-to-I editing targets using I-specific cleavage and exon array analysis, Molecular and Cellular Probes, Vol 27, 38-45 (2013), http://dx.doi.org/10.1016/j.mcp.2012.08.008. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Cancers often involve the synergistic effects of gene–gene interactions, but identifying these interactions remains challenging. Here, we present an odds ratio-based genetic algorithm (OR-GA) that is able to solve the problems associated with the simultaneous analysis of multiple independent single nucleotide polymorphisms (SNPs) that are associated with oral cancer. The SNP interactions between four SNPs—namely rs1799782, rs2040639, rs861539, rs2075685, and belonging to four genes (XRCC1, XRCC2, XRCC3, and XRCC4)—were tested in this study, respectively. The GA decomposes the SNPs sets into different SNP combinations with their corresponding genotypes (called SNP barcodes). The GA can effectively identify a specific SNP barcode that has an optimized fitness value and uses this to calculate the difference between the case and control groups. The SNP barcodes with a low fitness value are naturally removed from the population. Using two to four SNPs, the best SNP barcodes with maximum differences in occurrence between the case and control groups were generated by GA algorithm. Subsequently, the OR provides a quantitative measure of the multiple SNP synergies between the oral cancer and control groups by calculating the risk related to the best SNP barcodes and others. When these were compared to their corresponding non-SNP barcodes, the estimated ORs for oral cancer were found to be great than 1 [approx. 1.72–2.23; confidence intervals (CIs): 0.94–5.30, p

Alcohol ingestion–related increased left ventricular outflow tract (LVOT) pressure gradient in hypertrophic obstructive cardiomyopathy (HOCM) has been reported in the literature; however, acute myocardial infarction (AMI) after alcohol drinking in this patient group is rarely reported. Herein, we report a 68-year-old man with chronic alcoholism suffering from AMI after alcohol drinking. Electrocardiography revealed complete left bundle branch block, and chest X-ray showed acute pulmonary edema. Intubation was done for respiratory failure and intra-aortic balloon pump was also inserted for unstable hemodynamics. However, emergent coronary angiography revealed normal coronary arteries. HOCM was diagnosed by a high pressure gradient over LVOT and systolic anterior motion of mitral valve by echocardiography. This patient became stable under intensive care and medical treatment. This case reminds physicians that alcohol ingestion might cause AMI in HOCM patients because of increased LVOT pressure gradient and decreased coronary perfusion despite normal coronary arteries.

Single nucleotide polymorphisms (SNPs) play an important role in personalized medicine. However, the SNP data reported in many association studies provide only the SNP nucleotide/amino acid position, without providing the SNP ID recorded in National Center for Biotechnology Information databases. A tool with the ability to provide SNP ID identification, with a user-friendly interface, is needed. In this paper, a dynamic programming algorithm was used to compare homologs when the processed input sequence is aligned with the SNP FASTA database. Our novel system provides a web-based tool that uses the National Center for Biotechnology Information dbSNP database, which provides SNP sequence identification and SNP FASTA formats. Freely selectable sequence formats for alignment can be used, including general sequence formats (ACGT, [dNTP1/dNTP2] or IUPAC formats) and orientation with bidirectional sequence matching. In contrast to the National Center for Biotechnology Information SNP-BLAST, the proposed system always provides the correct targeted SNP ID (SNP hit), as well as nearby SNPs (flanking hits), arranged in their chromosomal order and contig positions. The system also solves problems inherent in SNP-BLAST, which cannot always provide the correct SNP ID for a given input sequence. Therefore, this system constitutes a novel application which uses dynamic programming to identify SNP IDs from the literature and keyed-in sequences for systematic association studies. It is freely available at http://bio.kuas.edu.tw/SNPosition/.

Hyperlipidemia can be effectively treated either with niacin or HMG-CoA reductase inhibitor (statin), or a combination of both. Few reports showed the effects of the combination regimen with niacin and statin on hemostatic functions. We conducted a single-center, double-blind, double-dummy, randomized, two-arm study to assess the effects of the niacin extended-release/lovastatin therapy in a fixed-dose formulation and of simvastatin on lipid lowering and two fibrinolytic parameters, fibrinogen and d-dimer. All patients were enrolled according to NCEP-ATP III guidelines and underwent a placebo run-in period of 4 weeks before being randomized to either niacin extended-release/lovastatin tablets (500/20 mg) once daily (n = 36) or simvastatin capsule (20 mg) once daily (n = 34). After 16 weeks of treatment, both groups of patients showed significantly reduced low-density lipoprotein cholesterol and total cholesterol (LDL-C, p < 0.001 and < 0.001, respectively, p = 0.159 between the groups; TC, p < 0.001 and < 0.001, respectively, p = 0.018 between the groups). Both drugs were well tolerated. Only in the group treated with niacin extended-release/lovastatin was fibrinogen concentration significantly reduced after treatment (2.48 ± 0.65 to 1.99 ± 0.62 g/L, p = 0.008). No difference was found with d-dimer in either group. This study shows that both niacin extended-release/ lovastatin and simvastatin are effective and well-tolerated lipid-lowering drugs in Taiwanese patients with dyslipidemia. A combinational treatment with niacin extended-release/lovastatin may provide additional benefit in fibrinolysis.

Antihypertensive agents may modulate fibrinolysis in addition to reducing blood pressure. We conducted a randomized trial to assess the effects of lercanidipine and losartan on blood pressure (BP) lowering and three fibrinolytic parameters: plasminogen activator inhibitor−1 (PAI-1), D-dimer, and fibrinogen. All patients enrolled had essential hypertension and underwent a placebo run-in period of 2 weeks before randomization to either lercanidipine tablets 10-20 mg once daily or losartan tablets 50-100 mg once daily. Twenty-six patients completed this study. After 8 weeks of treatment, both groups of patients had significantly reduced systolic (SBP) and diastolic BP (DBP) (SBP, p = 0.034 and 0.050, respectively; DBP, p = 0.018 and 0.034 for lercanidipine and losartan, respectively). Both drugs were well tolerated. Only in the group treated with lercanidipine was PAI-1 concentration significantly reduced (57.1 ± 4.7 to 43.1 ± 4.8 ng/ mL, p = 0.047). No difference was found with D-dimer and fibrinogen in either group. This study shows that both lercanidipine and losartan are effective antihypertensive drugs in patients with essential hypertension. Lercanidipine may provide additional benefit in fibrinolysis.

Cardiac troponin I (cTnI) has been found to be a sensitive and reliable marker of myocardial damage, and elevated levels of cTnI can indicate high risk for acute coronary syndrome. To determine how to intervene in possible cases of acute coronary syndrome, cTnI levels must be measured by immunoassay. However, cTnI immunoassay results are prone to interference from many substances such as heparin and common drugs. The contrast media used in the coronary angiography might also interfere with results. To explore this possibility, we performed two in vivo and two in vitro studies. In the first in vivo study, we evaluated the effects of contrast media on cTnI immunoassays by collecting blood samples from 45 patients undergoing coronary angiography before and after the procedure. We used the Opus Magnum immunoassay system to measure cTnI levels. In the second in vivo study, we collected 25 blood samples from another group of patients also undergoing angiography at various times before and after the procedure to determine cTnI values by both the Opus Magnum and ACCESS systems. In the first in vitro study, 12 different contrast media were treated as samples to disclose the potential interference of measurement in the two assay systems. In the second in vitro study, we made sequential dilutions of iopromide (Ultravist; Schering) with serum to explore their potential for interfering with the detection of cTnI by the Opus Magnum and ACCESS assays. In the first in vivo study using the Opus Magnum assay, cTnI concentrations in samples taken after angiography were significantly higher at 5 minutes than at 30 minutes, and, at 60 minutes, all cTnI concentrations had dropped below the cutoff point. In the second in vivo study, we found a substantial difference in detection of cTnI by the Opus Magnum and ACCESS assays. All cTnI concentrations checked by ACCESS assay were below the cutoff value. In our first in vitro study, the Opus Magnum assay gave false positive results for all 12 contrast media; the ACCESS assay gave a positive result for only one contrast medium, poppy-seed oil (Lipiodol; Guebert). In our second in vitro study, we found that, in the Opus Magnum assay, the more concentrated the contrast medium, the higher the cTnI value, but not in the ACCESS assay. We conclude that contrast media may cause false-positive results in cTnI assays and that, when contrast media are being used for angiography, cTnI results, especially those based on samples taken within the first hour of the procedure, should be interpreted carefully.

Vascular endothelial growth factor (VEGF) and transforming growth factor β (TGF-β1) play an important role in angiogenesis. We wanted to determine if concentrations of growth factors in the coronary sinus (CS) and right atrium (RA) are higher in coronary artery disease patients with total occlusions than in those with partial occlusions. Fifty-one patients scheduled for coronary artery angiography were evaluated for possible recruitment. A 6F Goodale-Lubin catheter was used to collect blood from the CS and RA. Data for all but four patients were gathered successfully, leaving 47 study patients. The reviewer was blinded to growth factor data when interpreting coronary angiographic findings. Of the 47 enrolled patients, 32 had at least one diseased vessel, seven of whom had at least one major total epicardial coronary occlusion. In all 32 patients, the concentrations of VEGF in the CS were higher than those in the RA (31.5 ± 2.7 vs 27.1 ± 1.8 pg/mL; p = 0.005). Patients with total occlusions had higher VEGF concentrations in the CS than those with non-total occlusions (38.9 ± 8.0 vs 29.5 ± 2.6 pg/mL; p = 0.037). The differences in TGF-β1 in the two groups were not statistically significant. The higher CS VEGF concentrations in patients with total occlusion indicate that VEGF may play a part in the development of angiogenesis.

Electrocardiographic changes in neurovascular disease are not rare. Patients with subarachnoid hemorrhage have electrocardiographic (ECG) abnormalities that may mimic ischemic heart disease and acute myocardial infarction. Outflow of catecholamines in the early stage of subarachnoid hemorrhage contributes to elevated blood pressure in most patients. Hypotension is a rare presentation in subarachnoid hemorrhage. We report a case of subarachnoid hemorrhage with transient ST elevation and intractable shock simulating acute myocardial infarction, and review the mechanism of ECG changes in subarachnoid hemorrhage.

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway., (Copyright © 2017 Kaohsiung Medical University. Published by Elsevier Taiwan. All rights reserved.)

Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance., (Copyright © 2017. Published by Elsevier Taiwan.)

Although an increasing number of RNA adenosine-to-inosine (A-to-I) editing sites are being discovered, how the editing frequencies of these sites are modulated to fine-tune protein function in adaptive responses is not well understood. A previous study screening for heat tolerance in Drosophila mutants discovered a hypnos-2 mutant strain that was later found to be defective in dADAR, the Drosophila gene encoding the A-to-I editing enzyme. This supports the hypothesis that cells and organisms respond to stressful environments by ADAR (adenosine deaminase acting on RNA)-mediated RNA editing. Here, we investigated changes in the RNA A-to-I editing frequencies of 30 Drosophila nervous system targets in response to heat shock, a stress acclimatization that requires the dADAR function. To our surprise, most of these nervous system editing targets showed reduced editing. Our results suggest that a change in RNA editing pattern is a mechanism by which organisms acclimate to drastic environmental change. However, how RNA editing confers heat resistance is more complicated and requires further investigation., (Copyright © 2013. Published by Elsevier B.V.)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disease characterized by replacement of myocardium with fibrofatty tissue. It mainly involves the right ventricle (RV) and causes abnormal RV performance. ARVC is the most common cause of sudden cardiac death in young Italian athletes because it induces malignant ventricular tachyarrhythmias. Clinical manifestations of ARVC may be different between Chinese and Western patients. In this paper, we share our experience of the clinical manifestations of ARVC and review previous reports of ARVC.

Several epidemiological studies have shown a positive correlation between chronic gastric infection with Helicobacter pylori (HP) and coronary artery disease. A number of reports also claimed that there are strong relationships between HP infection and coronary risk factors. However, clinical studies concerning the changes of coronary risk factors after eradication of HP infection are few and contradictory. We conducted a prospective study aiming to compare sugar, lipid and fibrinolytic profiles before HP eradication with those after HP eradication. HP infection was confirmed by endoscope-based examinations and eradicated by a standard OAC (omeperazole-amoxicillin-clarithromycin) regimen. We measured and compared pre- and post-eradication blood sugar, lipid profiles (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride) and fibrinolytic profiles (tissue-plasminogen activator, plasminogen activator inhibitor-1, fibrinogen, and D-dimer levels). Forty-eight patients (male:female, 25:23; mean age, 50.8 +/- 11.3 years) with gastric HP infection were enrolled in this study. Although HP infection was confirmed to have been successfully eradicated, no significant changes of blood fasting sugar, lipids or fibrinolytic profiles were found in patients after treatment. Coronary risk factors including fasting sugar, lipid and fibrinolytic profiles were not changed after successful HP eradication treatment. The relationship between HP infection and coronary artery disease needs to be clarified.

Thirty-one healthy subjects, aged 35 +/- 6 (21 to 48) years, were included in the study to evaluate the effect of ice water immersion on QT dispersion. There was no difference in the age between females (n = 11) and males (n = 20). Baseline, stress (at the end of ice water immersion, 4 degrees C, for 3 minutes) and recovery 12-lead electrocardiograms (ECGs) were recorded on each subject. During the test, a significant variability developed in both the QT dispersion (52 +/- 17, 68 +/- 25 and 59 +/- 21 ms; p = 0.015) and the corrected QT dispersion (56 +/- 17, 76 +/- 27 and 64 +/- 23 ms; p = 0.005), but not in the heart rate (74 +/- 11, 76 +/- 9, and 74 +/- 9 bpm, respectively; p = 0.447). There was no inter-sex difference in the baseline heart rate or QT dispersion, or in their response to ice water immersion. Age significantly correlated with the variation of QT dispersion to ice water immersion (r = 0.380, p = 0.035). With 37 years of age as a separation point, the variation of QT dispersion to ice water immersion was more obvious in the older group (28 +/- 22 vs. 10 +/- 19 ms, p = 0.023). In conclusion, cold may increase QT dispersion in healthy subjects, with a more obvious effect in the older ones.