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Find video protocols related to scientific articles indexed in Pubmed.
Targeting L1 cell adhesion molecule expression using liposome-encapsulated siRNA suppresses prostate cancer bone metastasis and growth.
Oncotarget
PUBLISHED: 10-09-2014
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The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in prostate cancer and its application in targeted gene therapy have not been investigated. Herein, we demonstrated that the L1CAM was expressed in androgen-insensitive and highly metastatic human prostate cancer cell lines. The correlation between L1CAM expression and prostate cancer metastasis was also validated in serum samples of prostate cancer patients. Knockdown of L1CAM expression in prostate cancer cells by RNA interference significantly decreased their aggressive behaviors, including colony formation, migration and invasion in vitro, and tumor formation in a metastatic murine model. These anti-malignant phenotypes of L1CAM-knockdown cancer cells were accompanied by G0/G1 cell cycle arrest and suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression and nuclear factor NF-?B activation. In vivo targeting of L1CAM expression using liposome-encapsulated L1CAM siRNAs effectively inhibited prostate cancer growth in mouse bone, which was associated with decreased L1CAM expression and cell proliferation by tumor cells. These results provide the first evidence for L1CAM being a major contributor to prostate cancer metastasis and translational application of siRNA-based L1CAM-targeted therapy.
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Hibiscus sabdariffa Polyphenols Alleviate Insulin Resistance and Renal Epithelial to Mesenchymal Transition: A Novel Action Mechanism Mediated by Type 4 Dipeptidyl Peptidase.
J. Agric. Food Chem.
PUBLISHED: 09-26-2014
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The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.
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Mulberry water extracts inhibit atherosclerosis through suppression of the integrin-??/focal adhesion kinase complex and downregulation of nuclear factor ?B signaling in vivo and in vitro.
J. Agric. Food Chem.
PUBLISHED: 09-16-2014
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Previous studies have shown that mulberry water extracts (MWEs), which contain polyphenolic compounds, have an antiatherosclerotic effect in vivo and in vitro through stimulating apoptosis of vascular smooth muscle cells (VSMCs). Histological analysis was performed on atherosclerotic lesions from high-cholesterol diet (HCD)-fed rabbits after treatment with 0.5-1% MWEs for 10 weeks. Immunohistochemistry showed that the expressions of SMA, Ras, and matrix metalloproteinase-2 in the VSMCs were dose-dependently inhibited after MWE treatment. The antimigratory effects of MWEs on A7r5 VSMCs were assessed by western blot analysis of migration-related proteins, visualization of F-actin cytoskeleton, and reverse transcription polymerase chain reaction. The results showed that MWEs inhibited VSMC migration through reducing interactions of the integrin-?3/focal adhesion kinase complex, alterations of the cytoskeleton, and downregulation of glycogen synthase kinase 3?/nuclear factor ?B signaling. Taken together, MWEs inhibited HCD-induced rabbit atherogenesis through blocking VSMC migration via reducing interactions of integrin-?3 and focal adhesion kinase and downregulating migration-related proteins.
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Hydrodynamic correlations and diffusion coefficient of star polymers in solution.
J Chem Phys
PUBLISHED: 09-01-2014
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The center-of-mass dynamics of star polymers in dilute solution is analyzed by hybrid mesoscale simulations. The fluid is modeled by the multiparticle collision dynamics approach, a particle-based hydrodynamic simulation technique, which is combined with molecular dynamics simulations for the polymers. Star polymers of various functionalities are considered. We determine the center-of-mass velocity correlation functions, the corresponding mean square displacements, and diffusion coefficients. The velocity correlation functions exhibit a functionality-dependent and structure-specific intermediate time regime, with a slow decay. It is followed by the long-time tail t(-3/2), which is solely determined by the fluid. Infinite-system-size diffusion coefficients are determined from the velocity correlation function by a combination of simulation and analytical results, as well as from the center-of-mass mean square displacement for various systems sizes and extrapolation. In terms of the hydrodynamic radius, the star polymer hydrodynamic diffusion coefficient exhibits the same universal system-size dependence as a spherical colloid. The functionality dependence of the ratio of hydrodynamic radii and the radii of gyration agrees well with experimental predictions.
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Long-term prognosis of patients with carbon monoxide poisoning: a nationwide cohort study.
PLoS ONE
PUBLISHED: 08-28-2014
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Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP[+]).
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Congenital right intermediate bronchial stenosis with carina trifurcation: successful management with slide tracheobronchial plasty.
Ann. Thorac. Surg.
PUBLISHED: 07-06-2014
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Congenital bronchial stenosis is rarely described and is difficult to manage. Here we report two cases of right intermediate bronchial stenosis (stenotic orifice with complete cartilage rings). Both cases were associated with ventricular septal defects, and a "trifurcation" pattern was found in both carinas. Both patients underwent surgical repair of the ventricular septal defects but could not be separated from ventilator support despite successful cardiac operations. Slide tracheobronchial plasty was applied to the right intermediate bronchus and lower trachea. After correction of the bronchial stenosis, both patients could be extubated and live without supplementary ventilation support.
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GRP78 mediates the therapeutic efficacy of curcumin on colon cancer.
Tumour Biol.
PUBLISHED: 07-03-2014
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Glucose-regulated protein 78 (GRP78) is the key regulator of endoplasmic reticular (ER) function. Expression of GRP78 was correlated with malignancy in different cancers. However, the role of GRP78 in the cytotoxic effect of curcumin on colon cancer cells is still unclear. A silencing RNA (siRNA) technique was used to knock down GRP78 expression. The anticancer effects of curcumin were assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a flow cytometric cell cycle analysis, and a terminal dexynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. HT-29 cells expressed lower GRP78 compared with DLD-1 cells. The MTT assay revealed that HT-29 cells were more resistant to curcumin treatment than DLD-1 cells. GRP78KD cells showed more resistance to curcumin treatment compared with scrambled control cells. Overexpressed GRP78 in HT-29 cells increased the sensitivity to curcumin treatment. According to the cell cycle analysis and TUNEL assay, we found that apoptosis dramatically increased in scrambled control cells compared to GRP78KD DLD-1 cells after curcumin treatment. Finally, we evaluated levels of Bcl-2, BAX, and Bad and found that an increase of Bcl-2 level was observed in GRP78KD cells treated with curcumin. Those results were consistent with the increasing of resistance to curcumin after silencing of GRP78. The levels of GRP78 expression might determine the therapeutic efficacy of curcumin against colon cancer cells.
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Heart transplantation in endstage rheumatic heart disease-experience of an endemic area.
Circ. J.
PUBLISHED: 06-26-2014
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Rheumatic heart disease (RHD) remains a significant cause of cardiovascular disease in developing countries. The nonsuppurative cardiovascular sequel of group A streptococcal infection is sustained inflammatory and immune reactions toward the myocardium and valves. This study attempted to determine the long-term outcome of heart transplantation in endstage RHD patients.Methods?and?Results:The 23 patients with endstage RHD at National Taiwan University Hospital between June 1987 and March 2012 were enrolled. In the same period, 226 dilated cardiomyopathy (DCM) patients were enrolled as the control group. The RHD group experienced more right ventricular failure and higher central venous pressure than the control group, which resulted in impaired liver and kidney function. The RHD patients had a lower 15-year survival rate than the DCM patients after transplantation (22.7% vs. 45.7%, P=0.038) and higher incidence of tricuspid regurgitation than the control group (32.2% vs. 11.4%). No differences existed between the groups for the mitral regurgitation rate (RHD 37.7% vs. DCM 29.4%, P=0.562).
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Increased regulatory T cells in patients with liver cirrhosis correlated with hyperbilirubinemia and predict bacterial complications.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-25-2014
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Patients with liver cirrhosis (LC) were regarded as immunocompromised status with high incidence of bacterial infection. Regulatory T cell (Treg cell) is known as an immune suppressor and also plays an important role in patients with sepsis.
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Hypotension, bedridden, leukocytosis, thrombocytopenia and elevated serum creatinine predict mortality in geriatric patients with fever.
Geriatr Gerontol Int
PUBLISHED: 06-15-2014
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The geriatric population (aged ?65 years) accounts for 12-24% of all emergency department (ED) visits. Of them, 10% have a fever, 70-90% will be admitted and 7-10% of will die within a month. Therefore, mortality prediction and appropriate disposition after ED treatment are of great concern for geriatric patients with fever. We tried to identify independent mortality predictors of geriatric patients with fever, and combine these predictors to predict their mortality.
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Patient perception of understanding health education and instructions has moderating effect on glycemic control.
BMC Public Health
PUBLISHED: 06-02-2014
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Whether health literacy is independently associated with processes or outcomes of diabetes-related care is controversial. We tried to demonstrate the interaction of health literacy and understanding of health education and instructions in achieving glycemic control.
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Mulberry water extracts inhibit rabbit atherosclerosis through stimulation of vascular smooth muscle cell apoptosis via activating p53 and regulating both intrinsic and extrinsic pathways.
J. Agric. Food Chem.
PUBLISHED: 05-23-2014
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Previous studies have shown that mulberry water extracts (MWEs), which contain polyphenolic compounds, have an antiatherosclerotic effect in rabbits. Apoptosis of vascular smooth muscle cells (VSMCs) is the key determinant of the number of VSMCs in remodeling. To improve the recovery from atherosclerosis pathology, it would be ideal to induce regression of atherosclerotic plaques and apoptosis of VSMCs. In this study, we treated high-cholesterol-diet-fed (HCD-fed) rabbits with MWEs, and we found that the MWEs effectively inhibited HCD-fed-induced intimal hyperplasia of vessel walls. We also found that MWEs initially activate JNK/p38 and p53, which in turn activate both Fas-ligand and mitochondria pathways, thereby causing mitochondria translocation of Bax and the reduction of Bcl-2 that trigger the cleavage of procaspases, finally resulting in apoptosis of VSMCs. In addition, 2.5-5.0 g/day of MWEs for humans may be enough to prevent atherosclerosis.
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Benzodiazepine & nonbenzodiazepine prescriptions for Taiwanese elderly with type 2 diabetes contributes to cognitive dysfunction.
Int Psychogeriatr
PUBLISHED: 05-15-2014
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This study examined the relationship of cognitive function and benzodiazepine/nonbenzodiazepine hypnotics (BZD/nonBZD) and other risk factors in a national sample of Taiwan's elderly diabetic patients.
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New Ce3+-activated thiosilicate phosphor for LED lighting-synthesis, luminescence studies, and applications.
ACS Appl Mater Interfaces
PUBLISHED: 05-06-2014
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A new Ce(3+)-activated thiosilicate phosphor, BaLa2Si2S8:Ce(3+), was synthesized by using solid-state methods in a fused silica ampule and found to crystallize in the structure type of La2PbSi2S8. The crystal structure has been characterized by synchrotron X-ray diffraction and refined with Rietveld methods. This novel cyan-emitting phosphor can be excited over a broad range from UV to blue light (380-450 nm) and generates a broadband emission peaking at 471 nm with a quantum efficiency of 36%. Nonradiative transitions between Ce(3+) ions in BaLa2Si2S8:Ce(3+) have also been demonstrated to be attributable to dipole-dipole interactions, and the critical distance was calculated to be 17.41 Å. When BaLa2Si2S8:Ce(3+) phosphor was utilized to incorporate with yellow-emitting (Sr,Ca)2SiO4:Eu(2+) phosphor and red-emitting CaAlSiN3:Eu(2+) phosphor on a 430 nm blue LED chip, a warm white light LED device with color rendering index of ?96 was obtained. The results indicate that cyan-emitting BaLa2Si2S8:Ce(3+) can serve as a potential phosphor for incorporation in fabrication of solid-state lighting. The preparation, spectroscopic characterization, quantum efficiency, decay lifetime, thermal-quenching behavior, and related LED device data are also presented.
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Glycemic Control Outcomes by Gender in the Pay-for-Performance System: A Retrospective Database Analysis in Patients with Type 2 Diabetes Mellitus.
Int J Endocrinol
PUBLISHED: 05-04-2014
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Background. The purpose of this study was to investigate how the degree of glycemic control in patients with type 2 diabetes associated with lifestyle interventions as well as sociodemographic factors and further examine the differences by gender. Methods. This was a retrospective study using data collected from a diabetes quality improvement plan that began in 2002 in a medical center in Taiwan. Statistic analysis was used to determine the associations of sociodemographic data, lifestyle intervention, and treatment regimens with changes in HbA1c levels (between the initial visit and the latest follow-up measured level), and the differences were then sorted by the sex of the patients. Results. Our results showed that HbA1c averaged 7.50% for males and 7.80% for females at the initial visit, compared to levels averaging 7.50% for males and 7.70% for females at the most recent follow-up visit. There was no significant change (P = 0.541) in HbA1c in males, but there was a 0.10% (P = 0.384) reduction in females. The duration of the diabetes and medication regimen was associated with the decrease seen in the females. Conclusions. The results of these analyses provide important insights for policy makers to formulate healthcare policies related to chronic diseases or illnesses.
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Second messengers mediating the proliferation and collagen synthesis of tenocytes induced by low-level laser irradiation.
Lasers Med Sci
PUBLISHED: 04-25-2014
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For decades, low-level laser therapy (LLLT) has widespread applications in tendon-related injuries. Although the therapeutic effect of LLLT could be explained by photostimulation of target tissue and cells, how tenocytes sense photonic energy and convert them into cascades of cellular and molecular events is still not well understood. This study was designed to elucidate the effects of LLLT on cell proliferation and collagen synthesis by examining the associated second messengers including ATP, Ca(2+), and nitric oxide using rat Achilles tenocytes. Moreover, proliferating cell nuclear antigen (PCNA) and transforming growth factor-?1 (TGF-?1) related to cell proliferation and matrix metabolism were also studied. The results showed that 904 nm GaAs laser of 1 J/cm(2) could significantly increase the MTT activity and collagen synthesis of tenocytes. Second messengers including ATP and intracellular Ca2+ were increased after laser treatment. Quantitative PCR analysis of tenocytes treated with laser revealed up-regulated expression of PCNA, type I collagen, and TGF-?1. Besides, laser-induced TGF-?1 expression was significantly inhibited by extracellular signal-regulated kinase (ERK) specific inhibitor (PD98059). The findings suggested that LLLT stimulated ATP production and increased intracellular calcium concentration. Directly or indirectly via production of TGF-?1, these second messengers mediated the proliferation of tenocytes and synthesis of collagen.
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Hyperbaric oxygen therapy as an effective adjunctive treatment for chronic Lyme disease.
J Chin Med Assoc
PUBLISHED: 04-13-2014
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Lyme disease is the most commonly reported vector-borne illness in the United States, but it is relatively rare in Taiwan. Lyme disease can be treated with antibiotic agents, but approximately 20% of these patients experience persistent or intermittent subjective symptoms, so-called chronic Lyme disease (CLD). The mechanisms of CLD remain unclear and the symptoms related to CLD are difficult to manage. Hyperbaric oxygen therapy (HBOT) was applied in CLD therapy in the 1990s. However, reported information regarding the effectiveness of HBOT for CLD is still limited. Here, we present a patient with CLD who was successfully treated with HBOT.
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Orangish-yellow-emitting Ca?Si?O?:Eu²? phosphor for application in blue-light based warm-white LEDs.
Dalton Trans
PUBLISHED: 04-09-2014
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A Eu(2+)-activated Ca3Si2O7:Eu(2+) orangish-yellow-emitting phosphor with strong luminescence was synthesized and its crystal structure was determined on the basis of XRD profiles using synchrotron radiation. The crystal structure was refined by the Rietveld refinement method. The excitation and emission spectra of the Ca3Si2O7:Eu(2+) phosphor show broad excitation bands in the range of 240-550 nm and a broad yellow emission band centered at 603 nm, depending on the concentration of Eu(2+). The optimized concentration of Eu(2+) in the Ca3Si2O7:Eu(2+) phosphor was determined to be 0.015 mol. The critical distance and average decay time were found to be short and fast, respectively, ranging from 19.74 Å to 13.69 Å and from 2.56 ?s to 2.34 ?s on increasing the Eu(2+) doping content. Warm-white light-emitting diodes (LEDs) fabricated using an InGaN-based blue LED chip combined with the Ca3Si2O7:0.015Eu(2+) phosphor gave color rendering indices between 76.0 and 38.9, correlated color temperatures between 1924 K and 4992 K, and tuned CIE chromaticity coordinates in the range from orangish-yellow (0.543, 0.389) to reddish purple (0.333, 0.219). The color coordinates and emission intensity of a Ca3Si2O7:0.015Eu(2+)-based white LED display were slightly yellow-shifted and the intensity increased on increasing the forward-bias current. These results indicate that orangish-yellow-emitting Ca3Si2O7:0.015Eu(2+) can serve as a promising candidate for applications in warm-white LEDs.
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Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension-A single-center experience in Taiwan.
J. Formos. Med. Assoc.
PUBLISHED: 04-08-2014
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Pulmonary endarterectomy (PEA) is a potentially curative surgical procedure for patients with chronic thromboembolic pulmonary hypertension. The aim of this study is to review our institutional experience with this operation.
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Sniff nasal inspiratory pressure does not decrease in elderly subjects.
J Phys Ther Sci
PUBLISHED: 02-27-2014
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[Purpose] Measurements of inspiratory strength are critical for detecting inspiratory muscle weakness. Sniff nasal inspiratory pressure (SNIP) is a quick, noninvasive measurement of global inspiratory strength; however, it is not clear how many trials are needed for reliable measurements. [Subjects and Methods] One hundred and nineteen subjects (age 39.9±16.5, range 18-69 yrs) completed the study. They were divided into subgroups of different ages and gender. Subjects were asked to take 20 maximal sniffs after normal expiration, with 30 seconds rest in-between. The highest values among the first 10 and last 10 SNIP maneuvers were recorded as SNIP1-10, and SNIP11-20, respectively. The paired t-test was used to compare the differences. Two-way measures ANOVA was used to compare the effects of age and gender on SNIP. [Results] SNIP 11-20 was significantly greater than SNIP1-10, suggesting that 10 trials is not enough to eliminate learning effects. Age did not affect SNIP in either gender, suggesting SNIP is preserved. In stepwise multiple linear regression analysis, the SNIP values were positively related with body mass index in women and positively related with weight in men. [Conclusion] The results suggest that twenty trials are needed for reliable SNIP measurements. The mean value and lower limits of normal SNIP are provided for clinical comparison.
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Supervised Phase II Cardiac Exercise Therapy Shortens the Recovery of Exercise Capacity in Patients with Acute Myocardial Infarction.
J Phys Ther Sci
PUBLISHED: 02-26-2014
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[Purpose] To investigate the effects of Phase II cardiac exercise therapy (CET) on exercise capacity and changes in coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Subjects] Thirty male subjects with AMI were divided into an experimental group (EG) and a control group (CG). Another 30 age-matched subjects with patent coronary arteries served as a normal-control group (NCG). [Methods] Subjects in EG (n=20) trained using a stationary bicycle for 30?min at their target heart rate twice a week for 8 weeks. Exercise capacity was defined as the maximal metabolic equivalents (METs) that subjects reached during the symptom-limited maximal exercise test. HR, BP and RPP were recorded. Subjects in EG and CG received exercise tests and screening for CRFs at the beginning of, end of, and 3 months after Phase II CET, while subjects in NCG participated only in the 1st test. [Results] METs of CG did not improve until the 3rd test, while RPP at the 2nd test showed a significant increase. However, EG showed increased METs at the 2nd test without increase of RPP, and increased their high density lipoprotein cholesterol (HDL-C) during the follow-up period between the 2nd and 3rd tests. [Conclusion] Phase II CET shortens the recovery time of exercise capacity, helps to maintain the gained exercise capacity and increases HDL-C in phase III.
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Novel Link of Anti-apoptotic ATF3 with Pro-apoptotic CTMP in the Ischemic Brain.
Mol. Neurobiol.
PUBLISHED: 02-22-2014
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Activating transcription factor 3 (ATF3) is a stress-induced transcription factor with diverse functions under disease states in multiple cell types. ATF3 has neuroprotective action against cerebral ischemia, which may involve caspase 3. However, the molecular mechanisms underlying ATF3 regulation of apoptosis are largely unknown. Here, we used gain- and loss-of-function and rescue approaches to demonstrate ATF3 attenuating hypoxic neuronal apoptosis. As well, the protective effect of ATF3 was mediated by downregulation of carboxyl-terminal modulator protein (CTMP), a pro-apoptotic factor that inhibits the anti-apoptotic Akt/PKB cascade. ATF3 (1) downregulated the mRNA and protein levels of CTMP; (2) its temporal expression pattern was reciprocal to that of CTMP; and (3) nuclear localization suggested that ATF3 may regulate CTMP transcription following hypoxic insult. Reporter assays demonstrated that ATF3 suppressed CTMP transcription, whereas ATF3 fusion with VP16, converting ATF3 to transcriptional activator, boosted CTMP transcription. By contrast, NF-?B increased CTMP transcription, and degradation-resistant I?B? decreased CTMP transcription. ChIP assays further confirmed that binding of ATF3 to the ATF/CREB site hindered NF-?B binding to the CTMP promoter, which repressed CTMP expression. Furthermore, CTMP siRNA treatment reduced hypoxic neuronal apoptosis by increasing p-Akt (Ser473) levels and leaving the upstream ATF3 level unchanged. We have identified an endogenous neuroprotective ATF3?CTMP signal cascade that may be a therapeutic target for reducing ischemic brain injury.
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A positive Babinski reflex predicts delayed neuropsychiatric sequelae in Chinese patients with carbon monoxide poisoning.
Biomed Res Int
PUBLISHED: 02-19-2014
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As the human population increased in China, the carbon monoxide is a serious environmental toxin in public health. However, predicting the delayed neuropsychiatric sequelae (DNS) of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of DNS in patients with COP. This study was conducted at four hospitals in China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. DNS was the primary endpoint. A positive Babinski reflex was the independent predictor for DNS: sensitivity = 53.8% (95% confidence interval [CI]: 26.1-79.6), specificity = 88.6% (95% CI: 83.7-92.1), positive predictive value (PPV) = 20.0% (95% CI: 9.1-37.5), and negative predictive value (NPV) = 97.3% (95% CI: 94.0-98.9). The area under the receiver operating characteristic curve = 0.712 (95% CI: 0.544-0.880). A positive Babinski reflex was very memorable, immediately available, and applicable in clinical practice. Even when the sensitivity and PPV of a positive Babinski reflex were unsatisfactory, it had a good specificity and NPV for excluding the risk of DNS. In patients without a positive Babinski reflex, the risk for DNS was only 2.7%. This finding may help physicians make decisions about dispositions for patients with COP.
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Diabetes-related avoidable hospitalizations in Taiwan.
Prim Care Diabetes
PUBLISHED: 01-28-2014
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An avoidable hospitalization (AH) is a condition that could have been prevented through effective treatment in outpatient care. Diabetes is often referred to as an ambulatory care-sensitive condition, and its associated hospitalizations are often referred to as avoidable hospitalizations. There are limited data on avoidable hospitalizations for individuals with diabetes in Taiwan.
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Multislice CT scans in patients on extracorporeal membrane oxygenation: emphasis on hemodynamic changes and imaging pitfalls.
Korean J Radiol
PUBLISHED: 01-24-2014
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This pictorial review provides the principles of extracorporeal membrane oxygenation (ECMO) support and associated CT imaging features with emphasis on the hemodynamic changes and possible imaging pitfalls encountered. It is important that radiologists in ECMO centers apply well-designed imaging protocols and familiarize themselves with post-contrast CT imaging findings in patients on ECMO.
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Hepatitis B virus X upregulates HuR protein level to stabilize HER2 expression in hepatocellular carcinoma cells.
Biomed Res Int
PUBLISHED: 01-13-2014
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Hepatitis B virus- (HBV-) associated hepatocellular carcinoma (HCC) is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx) has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR) family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2) is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.
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Physical activity is associated with decreased incidence of chronic kidney disease in type 2 diabetes patients: A retrospective cohort study in Taiwan.
Prim Care Diabetes
PUBLISHED: 01-09-2014
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To assess the effect of physical activity in patients with type 2 diabetes mellitus on prevention of diabetes with chronic kidney disease.
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Robotic mitral valve repair in infective endocarditis.
J Thorac Dis
PUBLISHED: 01-06-2014
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Robotic mitral surgery is the most common robotic cardiac procedures. However, in mitral endocarditis the repair become more challenging especially in minimally approach. We applied robotic surgery in mitral endocarditis repair and reviewed our surgical methods and results.
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Trichostatin A suppresses EGFR expression through induction of microRNA-7 in an HDAC-independent manner in lapatinib-treated cells.
Biomed Res Int
PUBLISHED: 01-04-2014
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Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, has been shown to improve the survival rate of patients with advanced HER2-positive breast cancers. However, the off-target activity of lapatinib in inducing EGFR expression without tyrosine kinase activity was demonstrated to render HER2-negative breast cancer cells more metastatic, suggesting a limitation to the therapeutic effectiveness of this dual inhibitor in HER2-heterogeneous tumors. Therefore, targeting EGFR expression may be a feasible approach to improve the anticancer efficiency of lapatinib-based therapy. Inhibition of HDAC has been previously reported to epigenetically suppress EGFR protein expression. In this study, however, our data indicated that treatment with HDAC inhibitors trichostatin A (TSA), but not suberoylanilide hydroxamic acid (SAHA) or HDAC siRNA, can attenuate both protein and mRNA expressions of EGFR in lapatinib-treated triple-negative breast cancer cells, suggesting that TSA may suppress EGFR expression independently of HDAC inhibition. Nevertheless, TSA reduced EGFR 3'UTR activity and induced the gene expression of microRNA-7, a known EGFR-targeting microRNA. Furthermore, treatment with microRNA-7 inhibitor attenuated TSA-mediated EGFR suppression. These results suggest that TSA induced microRNA-7 expression to downregulate EGFR expression in an HDAC-independent manner.
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Tuberculosis in developing countries: conditions for successful use of a decentralized approach in a rural health district.
Pan Afr Med J
PUBLISHED: 01-01-2014
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This article reports the results and the lessons learned from implementing the decentralized approach to tuberculosis (TB) detection and treatment, embedded with Human Immunodeficiency Virus (HIV) co-infection in health district. The objective was to increase the TB screening indicators in the district using the common ways for offering care to patients in health district.
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The Effect of Enterohemorrhagic E. coli Infection on the Cell Mechanics of Host Cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Enterohaemorrhagic E. coli (EHEC) is a type of human pathogenic bacteria. The main virulence characteristics of EHEC include the formation of attaching and effacing lesions (A/E lesions) and the production of one or more Shiga-like toxins, which may induce human uremic complications. When EHEC infects host cells, it releases translocated intimin receptor (Tir) and effector proteins inside the host cells, inducing the rearrangement and accumulation of the F-actin cytoskeleton, a phenotype leading to the formation of pedestals in the apical cell surface, and the growth of stress fibers at the base of the cells. To examine the effect of EHEC infection on cell mechanics, we carried out a series of experiments to examine HeLa cells with and without EHEC infection to quantify the changes in (1) focal adhesion area, visualized by anti-vinculin staining; (2) the distribution and orientation of stress fibers; and (3) the intracellular viscoelasticity, via directional video particle tracking microrheology. Our results indicated that in EHEC-infected HeLa cells, the focal adhesion area increased and the actin stress fibers became thicker and more aligned. The cytoskeletal reorganization induced by EHEC infection mediated a dramatic increase in the cytoplasmic elastic shear modulus of the infected cells, and a transition in the viscoelastic behavior of the cells from viscous-like to elastic-like. These changes in mechanobiological characteristics might modulate the attachments between EHEC and the host cell to withstand exfoliation, and between the host cell and the extracellular matrix, and might also alter epithelial integrity.
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Geriatric Fever score: a new decision rule for geriatric care.
PLoS ONE
PUBLISHED: 01-01-2014
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Evaluating geriatric patients with fever is time-consuming and challenging. We investigated independent mortality predictors of geriatric patients with fever and developed a prediction rule for emergency care, critical care, and geriatric care physicians to classify patients into mortality risk and disposition groups.
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N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor ?B (NF-?B), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-? (TNF-?) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-?B and MAPK pathways thereby increasing IL-1? and TNF-? production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.
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Development of a highly sensitive glycan microarray for quantifying AFP-L3 for early prediction of hepatitis B virus-related hepatocellular carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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The ?-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated oligosaccharide, has been investigated as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive glycan microarray assay. Sera from 9 patients with chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization therapy pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired tumor and non-tumor tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was significantly increased in tumorous tissues in these patients than that in non-tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new glycan microarray for the sensitive and rapid quantification of fucosylated AFP; this method is potentially applicable to screening changes in AFP-L3 level for assessment of HCC progression.
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Epidemiology and mortality among dialysis patients with parathyroidectomy: Taiwan ?National Cohort Study.
J. Nephrol.
PUBLISHED: 12-05-2013
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Background and objectives: Parathyroidectomy (PTx) is usually necessary in patients with end-stage renal disease (ESRD) on dialysis. Risk factors for higher PTx rates are controversial. The objectives of this study were to identify the risk factors for PTx in patients on dialysis and evaluate the mortality after PTx.  ?Methods: We analyzed data obtained from the National Health Insurance Research Database and included 35,162 ESRD dialysis patients. Kaplan-Meier method was used to calculate the incidence of PTx and survival rate after PTx. Cox proportional hazards models were used to identify the risk factors.  ?Results: The PTx rate was 8.09 per 1,000 patient-years. Stratified on the basis of gender and diabetic mellitus (DM), the highest incidence rate of PTx was in females without DM. Stratified by age and DM, the highest incidence rate of PTx was in those aged 18-44 years without DM. The significant risk factors for PTx were younger age, female (hazard ratio (HR) 1.409, 95% confidence interval (CI): 1.257-1.580), DM (HR 0.479, 95% CI: 0.413-0.555), peritoneal dialysis (HR 1.657, 95% CI: 1.418-1.938) and hypertension (HTN) (HR 1.317, 95% CI: 1.162-1.492). The cumulative survival rates after ?PTx were 97.1%, 94.5%, 82.8% and 77.4% at the first, second, fifth and seventh year, respectively. Only ?age was significantly associated with higher mortality ?after PTx.?Conclusions: Higher PTx rates were found in dialysis ?patients who were female and younger, did not have DM, were on peritoneal dialysis and had HTN. Advanced age was associated with a higher mortality after PTx.
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Risk Stratification and Outcome of Cardiac Surgery for Patients With Body Weight <2,500g in an Asian Center.
Circ. J.
PUBLISHED: 11-21-2013
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Background:?Cardiac surgery performed in patients with low body weight is a challenge for surgeons. Currently, such outcomes are mainly reported from European or North American centers. In this study, we review our cardiac surgery experience with neonates and infants weighing <2,500g. Methods and Results:?We included patients with a body weight <2,500g who received cardiac surgery between January 2008 and December 2012. The survival outcome was compared to that of patients with large body weight, and then the Risk Adjusted Classification for Congenital Heart Surgery (RACHS-1) categorization was used for operative risk stratification. In the 1,245 index operations, 53 patients (4.3%) were <2,500g. The mean body weight was 2,232g (range 1,320-2,500g). The hospital mortality rate was 20.7% (11/53). Most (85%) of the procedures were in RACHS-1 category ?3. The risk ratio was significantly higher in RACHS-1 category 3 (relative risk [RR]:6.2; 95% confidence interval [CI]:1.6-23.9) and 4 (RR:4.6; 95% CI:1.4-15.0), respectively, while it was not significantly different in category 2 (RR:1.02; 95% CI:1.01-1.02) and category 6 (RR:2.9; 95% CI:0.36-13.3). Conclusions:?Cardiac surgery performed on infants with low body weight is generally a complex procedure, but the results are acceptable. The risk was higher than that for patients with higher body weight in RACHS-1 category 3 and 4. Further investigation to improve the outcome of this high-risk group is needed.
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15-Deoxy-?(12,14)-PGJ 2, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis.
Mol. Neurobiol.
PUBLISHED: 10-17-2013
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15-Deoxy-?(12,14)-PGJ2 (15d-PGJ2) and thiazolidinedione attenuate reactive oxygen species (ROS) production via a peroxisome proliferator-activated receptor-gamma (PPAR-?)-dependent pathway. Nonetheless, how PPAR-? mediates ROS production to ameliorate ischemic brain injury is not clear. Recent studies indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in the vascular system. In the present study, we used an in vitro oxygen-glucose deprivation and reoxygenation (hypoxia reoxygenation [HR]) paradigm to study whether PPAR-? interacts with NADPH oxidase, thereby regulating ROS formation in cerebral endothelial cells (CECs). With pharmacological (PPAR-? antagonist GW9662), loss-of-function (PPAR-? siRNA), and gain-of-function (Ad-PPAR-?) approaches, we first demonstrated that 15d-PGJ2 protected HR-treated CECs against ROS-induced apoptosis in a PPAR-?-dependent manner. Results of promoter and subcellular localization analyses further revealed that 15d-PGJ2, by activating PPAR-?, blocked HR-induced NF-?B nuclear translocation, which led to inhibited transcription of the NADPH oxidase subunit p22phox. In summary, we report a novel transrepression mechanism whereby PPAR-? downregulates hypoxia-activated p22phox transcription and the subsequent NADPH oxidase activation, ROS formation, and CEC apoptosis.
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Antimetastatic effects of ?-carotene and possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells.
J. Agric. Food Chem.
PUBLISHED: 10-17-2013
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In vitro evidence suggests that ?-carotene (AC) is an antimetastatic agent against cancer cells, but the mechanistic action is unclear. This study investigated the antimetastatic effect and possible mechanism of AC in comparison with ?-carotene (BC) using human hepatocarcinoma SK-Hep-1 cells. Results reveal that treatment with AC (0.5-2.5 ?M) for 48 h significantly inhibited invasion, migration, and adhesion of SK-Hep-1 cells in a concentration-dependent manner. These effects of AC were stronger than those of BC at the same concentration (2.5 ?M). Mechanistically, AC significantly decreased activities of urokinase plasminogen activator and matrix metalloproteinases (MMP)-2 and -9, but increased protein expression of plasminogen activator inhibitor-1, tissue inhibitor of MMP (TIMP)-1 and -2, and nm23-H1, an antimetastatic protein. AC also attenuated focal adhesion kinase-mediated phosphorylation of mitogen-activated protein kinase family resulting in decreased protein expression of Rho and Rac 1. Overall, these data suggest that AC has potential as an antimetastatic agent.
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Mulberry 1-deoxynojirimycin pleiotropically inhibits glucose-stimulated vascular smooth muscle cell migration by activation of AMPK/RhoB and down-regulation of FAK.
J. Agric. Food Chem.
PUBLISHED: 10-02-2013
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Mulberry 1-deoxynojirimycin (DNJ), an inhibitor of ?-glucosidase, has been reported to help prevent diabetes mellitus and suppress lipid accumulation. The aim of this study was to determine whether mulberry DNJ has pleiotropic effects on the development of atherosclerosis. The mechanisms by which mulberry DNJ might inhibit migration of A7r5 vascular smooth muscle cells (VSMCs) under hyperglycemic conditions mimicking diabetes were investigated. The antimigratory effects of DNJ on VSMCs were assessed by Western blot analysis of migration-related proteins and by electric cell-substrate impedance sensing (ECIS) and visualization of F-actin cytoskeleton. Two pathways of DNJ-mediated inhibition of VSMC migration were identified. The first involved AMPK activation to inhibit fatty acid synthase (FASN) and Akt activity and then RhoB activation to inhibit nuclear factor-?B (NF-?B) and matrix metalloproteinase-2 (MMP) activity. The second involved inhibition of focal adhesion kinase (FAK), Ras, and RhoA activity leading to inhibition of F-actin activity.
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Perceptions on gender awareness and considerations in career choices of medical students in a medical school in Taiwan.
Kaohsiung J. Med. Sci.
PUBLISHED: 08-13-2013
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The trend of medical career choice in the younger generation has resulted in deficiency of manpower in the four major disciplines of internal medicine, surgery, obstetrics/gynecology, and pediatrics, which will threaten peoples health care in Taiwan. However, perceptions of gender awareness and factors affecting the career choices of medical students have not been investigated systemically in Taiwan. To explore the perceptions on gender awareness and considerations in career choices, we recruited 280 1(st)- and 7(th)-year male and female medical students at a Medical University for the study. A modified Nijmegen questionnaire using a 5-point Likert scale containing medical curricula (18 items), gender awareness (13 items), and career inclination (9 items) was adopted as the investigation tool in our study. The response rate was 75% (224/280). With regard to gender, the 1(st)-year male students had greater confidence in being a physician than the female students (p < 0.05), and female students subjectively suggested an advantage to communicate with patients or colleagues (p < 0.05). Faculty attitude in treating students differently by gender was more prominent in the 7(th)-year than in the 1(st)-year students (p < 0.001), and they felt male preceptors typically were more enthusiastic to teach and to rank higher grades to female than to male students; however, this was not observed among female preceptors. Both male and female students showed a low level of agreement that clinical skills and performance of a physician were significantly different by gender and "female physicians are more empathetic and provide more communications than male physicians". Factors influencing career choices of medical students, including "personal interests/talents" and "academic achievement of the specialty," were not significantly different by gender. Factors included "training and learning environments of the specialty", "risk of lawsuit", and "economic incentive" were more appreciated by the senior than the junior students (p < 0.05). Effect of "family" or "spouse" did not differ significantly regardless of gender or seniority. The 7(th)-year students had experiences in clinical medicine and had different considerations in career choice in comparison to the 1(st)-year students, and gender played a role in senior students. In addition, the senior rather than the junior students regarded "training and learning environments", "risk of lawsuit", and "economic incentive" as more important factors affecting the career choices, and male students paid more attention to these issues. Other factors such as fixed hours of duty with no emergency, easier lifestyle, and more time to take care his/her families were also important factors affecting career choice in medical students regardless of their gender; however, the junior students disclosed lower concern on the issues. In addition, four major misperceptions of gender and health issues were prevalent in the 7(th)-year students; therefore, we recognized the importance of integrating gender issues into medical curriculum to diminish gender misunderstanding and prejudice, and to provide gender-specific health care is mandatory in Taiwan.
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Lactobacillus plantarum MYL26 induces endotoxin tolerance phenotype in Caco-2 cells.
BMC Microbiol.
PUBLISHED: 08-06-2013
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Crohns disease and ulcerative colitis are the major types of chronic inflammatory bowel disease occurring in the colon and small intestine. A growing body of research has proposed that probiotics are able to attenuate the inflammatory symptoms of these diseases in vitro and in vivo. However, the mechanism of probiotic actions remains unclear.
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Polyphenols of Hibiscus sabdariffa improved diabetic nephropathy via attenuating renal epithelial mesenchymal transition.
J. Agric. Food Chem.
PUBLISHED: 07-29-2013
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We previously reported that Hibiscus sabdariffa polyphenol extracts (HPE) are beneficial for diabetic nephropathy. Since an epithelial to mesenchymal transition (EMT) is critical in renal fibrosis, the present study aimed to investigate whether HPE could prevent EMT of tubular cells. Treatment of HPE reduced angiotensin II receptors (AT)-1 and transforming growth factor ?1 (TGF-?1) evoked by high glucose and recovered the increased vimentin and decreased E-cadherin. HPE decreased fibronectin, thus avoiding EMT and accompanying fibrosis. AT-1 was upstream to TGF-?1, while there were recruitment signals between AT-1 and TGF-?1. Scan electron microscopy (SEM) and immunohistochemistry (IHC) revealed that the interacting filaments of tubular cells disappeared when treated with high glucose, and type IV collagen of tubulointerstitial decreased in diabetic kidneys. Treatment of HPE recovered morphological changes of cell junction and basement membrane. We suggest that HPE has the potential to be an adjuvant for diabetic nephropathy by regulating AT-1/TGF-?1 and EMT.
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Do Interleukin-10 and Superoxide Ions Predict Outcomes of Cardiac Extracorporeal Membrane Oxygenation Patients?
Antioxid. Redox Signal.
PUBLISHED: 07-26-2013
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Abstract Extracorporeal membrane oxygenation (ECMO) is used for cardiogenic shock rescue. It is hard to predict the outcome from this treatment by clinical observation in days soon after installation. We analyzed the plasma levels of interleukin (IL)-6, IL-8, IL-10, reactive oxygen species, and 8-OHdG, and the glutathione peroxidase activities from 23 cases at the time of ECMO installation before resuscitation. Generalized additive models (GAM) were performed to identify the death ranges of every variable, and the variables were further discretized. The impaired release of IL-10 on shock led to death. IL-10 levels at >16.58?pg/ml differentiated death from survival for acute myocardial infarction (AMI) patients, and levels at >143.17 pg/ml did the same for dilated cardiomyopathy (DCMP) patients. The prediction power of discretized IL-10 alone was measured as area under the curve (AUC) 0.913. The generalized linear model was then performed to predict the best composition from both the original and discretized variables and resulted in AUC 0.97 for the combined discretized IL-10 and superoxide ions. Two missed myocarditis cases from IL-10 prediction were resolved by superoxide ion levels. Our observations lead to the hypothesis that a proper response to cardiogenic shock by releasing the appropriate amount of IL-10 is required for survival in the cases of AMI and DCMP. For myocarditis, proper responses in IL-10 and superoxide ions are needed.
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Determinants of quality of life in children with cerebral palsy: A comprehensive biopsychosocial approach.
Res Dev Disabil
PUBLISHED: 07-23-2013
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This study investigated the determinants of quality of life (QOL) of children with cerebral palsy (CP) considering possible variables comprehensively from a biopsychosocial perspective by adopting the International Classification of Functioning, Disability and Health (ICF) and using a CP-specific QOL questionnaire. A total of 167 children with CP (mean age 9.06 years, SD 2.61 years) and their caregivers participated in this study. Childrens QOL was measured by the Cerebral Palsy Quality of Life for Children (CP QOL-Child) - primary caregiver proxy-report form. The potential determinants of QOL were collected based on all ICF dimensions. Results of seven multiple regression models showed that the determinants of QOL in children with CP were multidimensional and biopsychosocial in nature, i.e., encompassing the domains of health condition, body functions and structures, and contextual factors of the ICF. Childrens behavioral and emotional problems as well as caregivers psychological and family-related factors were important determinants of QOL in children with CP. Knowledge of the determinants of QOL could serve as a guide in a holistic approach to evaluation and intervention targeted at these determinants to improve the QOL of children with CP.
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Various predictors of sustained virologic response in different age groups of patients with genotype-1 chronic hepatitis C.
J. Clin. Gastroenterol.
PUBLISHED: 07-12-2013
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Age is one of the sustained virologic response (SVR) predictors for genotype-1 chronic hepatitis C patients treated with pegylated interferon-?/ribavirin. However, variation of SVR predictors in different age groups was not explored before. We therefore conducted this study for investigating this issue.
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Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate.
Transl Res
PUBLISHED: 06-27-2013
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Nitric oxide (NO) deficiency mediates oxidative stress in the kidney and is involved in the development of hypertension. NO synthesis occurs via 2 pathways: nitric oxide synthase (NOS) dependent and NOS-independent. We tested whether the development of hypertension is prevented by restoration of NO by dietary l-citrulline or nitrate supplementation in young spontaneously hypertensive rats (SHRs). Male SHRs and normotensive Wistar Kyoto control rats (WKYs)s age 4 weeks were assigned to 4 groups: untreated SHRs and WKYs, and SHRs and WKYs that received 0.25% l-citrulline for 8 weeks. In our second series of studies, we replaced l-citrulline with 1 mmol/kg/d sodium nitrate. All rats were sacrificed at age 12 weeks. We found an increase in the blood pressure of SHRs was prevented by dietary supplementation of l-citrulline or nitrate. Both treatments restored NO bioavailability and reduced oxidative stress in SHR kidneys. l-Citrulline therapy reduced levels of l-arginine and asymmetric dimethylarginine (ADMA)-an endogenous inhibitor of NOS-and increased the l-arginine-to-ADMA ratio in SHR kidneys. Nitrate treatment reduced plasma levels of l-arginine and ADMA concurrently in SHRs. Our findings suggest that both NOS-dependent and -independent approaches in the prehypertensive stage toward augmentation of NO can prevent the development of hypertension in young SHRs.
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Determinants of school activity performance in children with cerebral palsy: a multidimensional approach using the ICF-CY as a framework.
Res Dev Disabil
PUBLISHED: 06-13-2013
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This study aimed to identify the determinants of activity performance in children with cerebral palsy (CP) in school by considering factors from the entire scope of the International Classification of Functioning, Disability, and Health for Child and Youth (ICF-CY). A sample of 167 school-aged children with CP and their caregivers were recruited in the study. Activity performance in school settings was assessed with part 3 of the School Functional Assessment - Chinese version, which divides activity performance into performance of physical activities and cognitive/behavioral activities. Possible determinants were collected according to all dimensions of the ICF-CY. Multiple regression analyses showed that the determinants of performance of physical activities were receiving speech therapy in school, diplegia, having a domestic helper, and severity of gross and fine motor impairments, explaining 83% of the total variance; the determinants of performance of cognitive/behavioral activities were intellectual impairment, prosocial behavior, having an assistant in school, educational placement, severity of fine motor impairment, accounting for 73% of the total variance. Results of the study provide clinicians a holistic understanding of factors influencing school activity performance, and enable clinicians to make appropriate evaluations and interventions targeted at the determinants to enhance childrens activity performance in school.
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Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes.
Diabetes Res. Clin. Pract.
PUBLISHED: 06-10-2013
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To compare the efficacy and safety of acarbose plus metformin fixed-dose combination (FDC) versus acarbose monotherapy for type 2 diabetes (T2D).
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Crossover chimney technique to preserve the internal iliac artery in abdominal aortic aneurysm with common iliac artery aneurysms.
J. Endovasc. Ther.
PUBLISHED: 06-05-2013
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To report a new technique to preserve the internal iliac artery (IIA) in cases of aortoiliac aneurysms.
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Brefeldin a effectively inhibits cancer stem cell-like properties and MMP-9 activity in human colorectal cancer colo 205 cells.
Molecules
PUBLISHED: 05-30-2013
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Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A (BFA) is an antibiotic that is known to block protein transport and induce endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the survival of suspension Colo 205 cells (IC?? = ~15 ng/mL) by inducing apoptosis, and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation assay and soft agar colony formation assay in the same nanogram per milliliter range. We also discovered that at such low concentrations, BFA effectively induced endoplasmic reticulum (ER) stress response as indicated by the increased mRNA expression of ER stress-related genes, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP). Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP-9). These findings suggest that BFA can effectively suppress the progression of colorectal cancer during the tumorigenesis and metastasis stages. These results may lead to the development of novel therapies for the treatment of colorectal cancer.
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Hepatitis B Virus-Encoded X Protein Downregulates EGFR Expression via Inducing MicroRNA-7 in Hepatocellular Carcinoma Cells.
Evid Based Complement Alternat Med
PUBLISHED: 05-23-2013
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Hepatitis B virus (HBV) infection accounts for over a half of cases of hepatocellular carcinoma (HCC), the most frequent malignant tumor of the liver. HBV-encoded X (HBx) plays critical roles in HBV-associated hepatocarcinogenesis. However, it is unclear whether and how HBx regulates the expression of epidermal growth factor receptor (EGFR), an important gene for cell growth. Therefore, the study aimed to investigate the association between HBx and EGFR expression. In this study, we found that HBx upregulates miR-7 expression to target 3UTR of EGFR mRNA, which in turn results in the reduction of EGFR protein expression in HCC cells. HBx-mediated EGFR suppression renders HCC cells a slow-growth behavior. Deprivation of HBx or miR-7 expression or restoration of EGFR expression can increase the growth rate of HCC cells. Our data showed the miR-7-dependent EGFR suppression by HBx, supporting an inhibitory role of HBx in the cell growth of HCC. These findings not only identify miR-7 as a novel regulatory target of HBx, but also suggest HBx-miR-7-EGFR as a critical signaling in controlling the growth rate of HCC cells.
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Quantitative flow measurement by digital subtraction angiography in cerebral carotid stenosis using optical flow method.
J Xray Sci Technol
PUBLISHED: 05-23-2013
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We analyzed intracranial regional blood flows using an optical flow method (OFM) and digital subtraction angiography in patients with internal carotid artery (ICA) stenosis. We also retrospectively explored the correlation between the patients diagnoses and the severity of the ICA stenoses.
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Risk of musculoskeletal disorder among Taiwanese nurses cohort: a nationwide population-based study.
BMC Musculoskelet Disord
PUBLISHED: 04-15-2013
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Musculoskeletal disorders (MSDs) represent the leading causes of occupational injuries among nursing staff. This population-based study was designed to assess the incidence and age-specific incidence of MSDs among a Taiwanese nurse cohort compared with non-nurses.
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Concomitant slide tracheoplasty and cardiac operation for congenital tracheal stenosis associated with VACTERL.
Ann. Thorac. Surg.
PUBLISHED: 04-08-2013
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The association of congenital tracheal stenosis and tracheoesophageal (TE) fistula is rare. Here, we report 2 patients with tracheobronchial stenosis (complete cartilage ring) involving the lower trachea and right bronchus. Both patients had associated VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies, TE, renal, and limb defects) congenital cardiac defects and tracheal diverticula after repair of the TE fistula in type C esophageal atresia. The stenotic segment began at the orifice of the TE fistula, which became diverticula after the TE fistula was repaired. Concomitant repair of congenital cardiac defects and a slide tracheoplasty with elimination of the diverticula were performed successfully.
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MicroRNA-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through nuclear factor kappa B pathways.
Hepatology
PUBLISHED: 04-05-2013
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Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Dysregulation of miR-657 has been observed in several types of cancers, but its biological function is still largely unknown. Our results showed that miR-657 expression can be induced by hepatitis viral proteins and is significantly increased in hepatocellular carcinoma (HCC) tissues. Moreover, introduction of miR-657 dramatically increases proliferation and colony formation of HCC cells in vitro and induces tumor development in immunodeficient mice. Further studies showed that miR-657 directly targets the transducin-like enhancer protein 1 (TLE1) 3 untranslated region (UTR) and activates nuclear factor kappa B (NF-?B) pathways that contribute to hepatocarcinogenesis. Conclusion: This study identified a mechanism whereby miRNA-657 contributed to HCC through novel cancer pathways and provides new insights into the potential molecular mechanisms of hepatic carcinogenesis.
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Sleep apnoea patients have higher mortality when confronting sepsis.
Eur. J. Clin. Invest.
PUBLISHED: 04-02-2013
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Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea.
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Efficacy and safety of intermittent hemodialysis in infants and young children with inborn errors of metabolism.
Pediatr. Nephrol.
PUBLISHED: 04-01-2013
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Intermittent hemodialysis (IHD) is the most efficient form of renal replacement therapy (RRT) for removing toxic substances from patients bodies. However, the efficacy and safety of IHD in infants and young children with inborn errors of metabolism are still not clear.
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Lapatinib--induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors.
Breast Cancer Res.
PUBLISHED: 03-27-2013
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Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed.
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Downregulation of microRNA-15b by hepatitis B virus X enhances hepatocellular carcinoma proliferation via fucosyltransferase 2-induced Globo H expression.
Int. J. Cancer
PUBLISHED: 03-24-2013
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Globo H, a cancer-associated carbohydrate antigen, is highly expressed in various types of cancers. However, the role of Globo H in hepatocellular carcinoma (HCC) remains elusive. In our study, we performed glycan microarray analysis of 134 human serum samples to explore anti-Globo H antibody changes and found that Globo H is upregulated in hepatitis B virus (HBV)-positive HCC. Similarly, immunohistochemistry showed that Globo H expression was higher in tumors compared to normal tissues. In addition, fucosyltransferase 2 (FUT2), the main synthetic enzyme of Globo H, was also increased in HCC cells overexpressing HBV X protein (HBX). HBX plays an important role in promoting cell proliferation and may be related to increased levels of FUT2 and Globo H. Furthermore, using microRNA profiling, we observed that microRNA-15b (miR-15b) was downregulated in patients with HCC and confirmed association of FUT2 expression with expression of its product, Globo H. Therefore, our results suggest that HBX suppressed the expression of miR-15b, which directly targeted FUT2 and then increased levels of Globo H to enhance HCC cell proliferation. Additionally, proliferation of HBX-overexpressing HCC cells was significantly inhibited by treatment with Globo H antibody in vitro. In xenograft animal experiments, we found that overexpression of miR-15b effectively suppressed tumor growth. The newly identified HBX/miR-15b/FUT2/Globo H axis suggests one possible molecular mechanism of HCC cell proliferation and represents a new potential therapeutic target for HCC treatment.
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Chinese nomogram to predict probability of positive initial prostate biopsy: a study in Taiwan region.
Asian J. Androl.
PUBLISHED: 03-08-2013
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Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chinese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Chinese male population. Data were collected from 893 Chinese male referrals, 697 in the derivation set and 196 in the external validation set, who underwent initial prostate biopsies as individual screening. We analyzed age, prostate volume, total prostate-specific antigen (PSA), PSA density (PSAD), digital rectal examinations (DRE) and transrectal ultrasound (TRUS) echogenicity. Logistic regression analysis estimated odds ratio, 95% confidence intervals and P values. Independent predictors of a positive biopsy result included advanced age, small prostate volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver-operating characteristic curve for the model was 88.8%, which was greater than that of the prediction based on total PSA alone (area under the receiver-operating characteristic curve 74.7%). If externally validated, the predictive probability was 0.827 and the accuracy rate was 78.1%, respectively. Incorporating clinical and laboratory data into a prebiopsy nomogram improved the prediction of prostate cancer compared with predictions based solely on the individual factors.
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EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors.
Prostate
PUBLISHED: 03-05-2013
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Overexpression of epidermal growth factor receptor (EGFR) is associated with poor prognosis in malignant tumors. Sodium/glucose co-transporter 1 (SGLT1) is an active glucose transporter that is overexpressed in many cancers including prostate cancer. Previously, we found that EGFR interacts with and stabilizes SGLT1 in cancer cells.
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Comparative proteomic analysis of peritoneal dialysate from chronic glomerulonephritis patients.
Biomed Res Int
PUBLISHED: 02-22-2013
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Peritoneal dialysis (PD) frequently contributes to peritoneal damage which cannot be easily identified without invasive techniques, implying the urgent need for biomarkers and revealing mechanisms. Chronic glomerulonephritis (CGN) is one of the leading causes of receiving dialysis treatment. Here, we attempted to analyze the peritoneal dialysate collected from CGN patients when they receive continuous ambulatory peritoneal dialysis (CAPD) treatment for the first time and after a year to reveal the protein changes that resulted from PD. Proteins were displayed by two-dimensional gel electrophoresis (2DE). Altered gel spots were digested followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for protein identification. Eight proteins were found to have differential expression levels between two groups. Their differential expressions were validated by Western blots in other sets of peritoneal dialysates. Proteins identified with higher levels in the first-time dialysate suggested their dominant appearance in CGN patients, while those that showed higher levels in peritoneal dialysate collected after one year may result from initial peritoneal inflammation or changes in the permeability of the peritoneum to middle-sized proteins. All the identified proteins may provide a perceptiveness of peritoneal changes caused by PD and may function as potential biomarkers or drug targets.
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Predicting the hyperglycemic crisis death (PHD) score: a new decision rule for emergency and critical care.
Am J Emerg Med
PUBLISHED: 02-04-2013
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We investigated independent mortality predictors of hyperglycemic crises and developed a prediction rule for emergency and critical care physicians to classify patients into mortality risk and disposition groups.
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Oat prevents obesity and abdominal fat distribution, and improves liver function in humans.
Plant Foods Hum Nutr
PUBLISHED: 02-02-2013
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Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ?27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders.
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Psoriasis is associated with an increased risk of parkinsonism: a population-based 5-year follow-up study.
J. Am. Acad. Dermatol.
PUBLISHED: 01-29-2013
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Few studies have examined the association between autoimmune diseases and parkinsonism.
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Lapatinib-mediated cyclooxygenase-2 expression via epidermal growth factor receptor/HuR interaction enhances the aggressiveness of triple-negative breast cancer cells.
Mol. Pharmacol.
PUBLISHED: 01-25-2013
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Lapatinib, a dual epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) kinase inhibitor, showed clinical benefits in advanced HER2-positive breast cancer patients. Because some triple-negative breast cancers (TNBCs) frequently overexpress EGFR, the antitumor activity of lapatinib in such diseases was also tested. However, the results showed a worse event-free survival rate. It remains unknown whether and how lapatinib elicits the aggressiveness of such cancer cells. In this study, our results demonstrated that lapatinib facilitated axillary and lung metastases of triple-negative MDA-MB-231 breast cancer cells without affecting their viability, leading to worse survival in orthotopic xenograft mice. The lapatinib-increased motility was attributed by the elevation of EGFR through the downregulation of microRNA-7 and by the subsequent overexpression of cyclooxygenase-2 (COX-2). Strikingly, independent of its kinase activity, the elevated EGFR at least partly stabilized COX-2 expression by enhancing the binding of HuR to COX-2 mRNA. Our results suggest that lapatinib may increase the migration and invasion of MDA-MB-231 cells by upregulating EGFR and COX-2 through the downregulation of microRNA-7, providing a potential explanation for the worse clinical outcome of TNBC patients who receive lapatinib-based treatment. These findings also shed new light on the molecular mechanism of COX-2 mRNA stabilization by EGFR in a kinase-independent manner.
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Cancer History, Bandemia, and Serum Creatinine Are Independent Mortality Predictors in Patients with Infection-Precipitated Hyperglycemic Crises.
BMC Endocr Disord
PUBLISHED: 01-13-2013
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Infection is the most common precipitating factor and cause of death in patients with hyperglycemic crises. Treating infection-precipitated hyperglycemic crises includes using empiric antibiotics early; correcting dehydration, hyperglycemia, and electrolyte imbalances; and frequent monitoring. Intensive care unit admission, broad-spectrum antibiotics, and even novel therapy for infection may be beneficial for patients with a high risk of mortality. However, these management options are costly and not beneficial for every patient. Selecting high-risk patients who would most likely benefit is more appropriate. We investigated the independent mortality predictors of patients with infection-precipitated hyperglycemic crises to facilitate clinical decision making.
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Beyond NF-?B activation: nuclear functions of I?B kinase ?.
J. Biomed. Sci.
PUBLISHED: 01-11-2013
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I?B kinase (IKK) complex, the master kinase for NF-?B activation, contains two kinase subunits, IKK? and IKK?. In addition to mediating NF-?B signaling by phosphorylating I?B proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-?B. Although these two kinases share structural and biochemical similarities, different sub-cellular localization and phosphorylation targets between IKK? and IKK? account for their distinct physiological and pathological roles. While IKK? is predominantly cytoplasmic, IKK? has been found to shuttle between the cytoplasm and the nucleus. The nuclear-specific roles of IKK? have brought increasing complexity to its biological function. This review highlights major advances in the studies of the nuclear functions of IKK? and the mechanisms of IKK? nuclear translocation. Understanding the nuclear activity is essential for targeting IKK? for therapeutics.
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Outcomes following endovascular or open repair for ruptured abdominal aortic aneurysm in a Chinese population.
Heart Vessels
PUBLISHED: 01-11-2013
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To determine whether emergent endovascular repair (eEVAR) can be an alternative for anatomically suitable ruptured abdominal aortic aneurysms (RAAA) in a Chinese population compared to open aneurysm repair (OAR), 36 patients with RAAA undergoing either OAR or eEVAR in National Taiwan University Hospital from 2005 to 2012 were analyzed retrospectively. Thirty-five (97.2 %) patients were treated. Among them, 20 (57.1 %) were treated by OAR and 15 (42.9 %) by eEVAR. The overall 30-day survival rate was 77.1 %. There was no significant difference in 30-day mortality rate (OAR 15.0 % vs. eEVAR 33.3 %, p = 0.201) and midterm mortality rate (OAR 20.0 % vs. eEVAR 46.7 %, p = 0.093) between these two groups. On univariate analysis, free peritoneal rupture (p < 0.001), pre-operative shock (p = 0.001) and female gender (p = 0.016) are related to a higher 30-day mortality rate, while free peritoneal rupture (p = 0.012) and pre-operative shock (p = 0.030) are associated with a higher midterm mortality rate in both repair techniques. On multivariate analysis, free peritoneal rupture was associated with higher 30-day (OR 26.0, 95 % CI 2.2-295.6, p = 0.009) and midterm (OR 13.1, 95 % CI 1.2-37.6, p = 0.032) mortality rates. In patients with RAAA, there is no significant difference in 30-day mortality and midterm mortality between eEVAR and OAR groups in our study. eEVAR could be an alternative therapy for anatomically suitable RAAA in a Chinese population.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.