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Find video protocols related to scientific articles indexed in Pubmed.
Proliferative epithelial disease identified in nipple aspirate fluid and risk of developing breast cancer: A systematic review.
Curr Med Res Opin
PUBLISHED: 11-19-2014
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Abstract Background: Guideline panels recognize the need to increase the accuracy of identifying women at high risk of developing breast cancer who would benefit from prevention strategies. The characterization of proliferative epithelial disease found in nipple aspirate fluid (PED-NAF) may be a relevant risk factor. Objective: To comprehensively review the published literature to characterize and summarize abnormal cytology detected by NAF and the association of PED-NAF with subsequent risk of developing breast cancer. Research design and methods: Literature identified by systematic searches in MEDLINE PubMed and the Cochrane Library was screened for articles containing primary data on NAF cytology based on predefined inclusion and exclusion criteria. Main outcome measures: Study characteristics, cytological group distribution, and incidence of breast cancer. Results: Thirty articles were included after full-text review, of which 16 were analyzed, containing data on 20,808 unique aspirations from over 17,378 subjects. Seven (44%) of the studies used the King cytological classification system. Among aspirations from women free of breast cancer, 51.5% contained fluid, in which over 27.7% had PED on cytology. In the 2 prospective studies of 7,850 cancer-free women, abnormal cytology by NAF carried a 2.1-fold higher risk (95% CI, 1.6-2.6; p < 0.001) of developing breast cancer, compared with women from whom no fluid could be obtained. Conclusions: PED-NAF among women free of breast cancer, compared with no fluid being obtained, has an independent risk of developing breast cancer comparable to the risk of a woman with a positive family history of breast cancer. These findings have implications for augmenting risk prediction and clinical decisions concerning breast cancer surveillance and chemoprevention. As with all reviews, heterogeneity across studies may have influenced the results. The limited literature calls for prospective studies on asymptomatic women with long-term follow-up.
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Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan.
BMC Gastroenterol
PUBLISHED: 11-18-2014
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BackgroundOsteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan.MethodsA total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts.ResultsDuring the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01).ConclusionPatients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.
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A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth Through HIF-1/2?
J. Biol. Chem.
PUBLISHED: 11-14-2014
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The calcium permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of Forkhead transcription factor 3a (FOXO3a) and superoxide dismutase 2 (MnSOD). Cells expressing dominant negative short isoform (TRPM2-S) had reduced FOXO3a and MnSOD levels, reduced calcium influx in response to oxidative stress, and enhanced ROS, leading to decreased cell viability. Here, in xenografts generated with SH-SY5Y neuroblastoma cells stably expressing TRPM2 isoforms, growth of tumors expressing TRPM2-S was significantly reduced compared to tumors expressing TRPM2-L. Expression of HIF-1/2? was significantly reduced in TRPM2-S expressing tumor cells, as was expression of target proteins regulated by HIF-1/2? including those involved in glycolysis (LDHA, ENO2), oxidant stress (FOXO3a), angiogenesis (VEGF), mitophagy and mitochondrial function (BNIP3 and NDUFA4L2), and mitochondrial electron transport chain activity (complex IV, cytochrome oxidase 4.1/4.2). The reduction in HIF-1/2? was mediated both through significantly reduced HIF-1/2? mRNA levels and increased levels of von Hippel-Lindau in TRPM2-S expressing cells. Inhibition of TRPM2-L by pretreatment with clotrimazole or expression of TRPM2-S significantly increased sensitivity of cells to doxorubicin. Reduced survival of TRPM2-S expressing cells after doxorubicin was rescued by gain of HIF-1 or 2? function. These data suggest that TRPM2 activity is important for tumor growth, and cell viability and survival following doxorubicin, and that interference with TRPM2-L function may be a novel approach to reduce tumor growth through modulation of HIF-1/2?, mitochondrial function and mitophagy.
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Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling.
Nucleic Acids Res.
PUBLISHED: 11-02-2014
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Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5' untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR.
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A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells.
Nucleic Acids Res.
PUBLISHED: 10-28-2014
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The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10(5) copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5' untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES.
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Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study.
Intest Res
PUBLISHED: 09-26-2014
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Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria.
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Long-term clinical outcome of major adverse cardiac events in survivors of infective endocarditis: a nationwide population-based study.
Circulation
PUBLISHED: 09-15-2014
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Substantial infective endocarditis (IE)-related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors.
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Association of postdischarge rehabilitation with mortality in intensive care unit survivors of sepsis.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-12-2014
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Intensive care unit (ICU)-acquired weakness is a common issue for sepsis survivors that is characterized by impaired muscle strength and causes functional disability. Although inpatient rehabilitation has not been found to reduce in-hospital mortality, the impact of postdischarge rehabilitation on sepsis survivors is uncertain.
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PlGF mediates neutrophil elastase-induced airway epithelial cell apoptosis and emphysema.
Respir. Res.
PUBLISHED: 09-05-2014
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BackgroundChronic pulmonary obstructive disease (COPD) has become the fourth leading cause of death worldwide. Cigarette smoking induces neutrophil elastase (NE) and contributes to COPD, but the detailed mechanisms involved are not fully established. In an animal model of pulmonary emphysema, there are increased expressions of placenta growth factor (PlGF) and lung epithelial (LE) cell apoptosis. This study hypothesized that excessive NE may up-regulate PlGF and that PlGF-induced LE apoptosis mediates the pathogenesis of pulmonary emphysema.MethodsHuman bronchial epithelial cells, BEAS-2B, and primary mouse type II alveolar epithelial cells were treated with NE. The PlGF promoter activity was examined by luciferase activity assay, while PlGF expression and secretion were evaluated by RT-PCR, Western blotting, and ELISA. Both cell lines were treated with PlGF to evaluate its effects and the downstream signaling pathways leading to LE cell apoptosis. PlGF knockout and wild-type mice were instilled with NE to determine the roles of PlGF and its downstream molecules in NE-promoted mice pulmonary apoptosis and emphysema phenotype.ResultsThe transcriptional factor, early growth response gene-1, was involved in the NE-promoted PlGF promoter activity, and the expression and secretion of PlGF mRNA and protein in LE cells. PlGF-induced LE cell apoptosis and NE-induced mice pulmonary apoptosis and emphysema were mediated by the downstream c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)¿ signaling pathways.ConclusionThe NE-PlGF-JNK/PKC¿ pathway contributes to the pathogenesis of LE cell apoptosis and emphysema. PlGF and its downstream signaling molecules may be potential therapeutic targets for COPD.
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Factors influencing the clinical expression of intermediate CAG repeat length mutations of the Huntington's disease gene.
J. Neurol.
PUBLISHED: 08-29-2014
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Our aim is to elucidate the clinical variables associated with the development of manifest HD in patients with intermediate CAG repeat lengths. 2,167 participants were seen throughout 44 research sites in the United States, Canada or Australia over a five-year natural history observational study (2006-2011) (Trial # NCT00313495). The Chi-square test and a generalised linear model were used to examine the differences in demographics and cognitive tests among three groups of CAG repeat length. The mixed model was then used to examine the time effect on cognitive assessments by CAG groups. No patient with CAG repeat length 27-35 developed manifest HD, whereas three patients with 36-39 did. Total motor score, maximal chorea score and maximal dystonia score were significantly different at baseline (p < 0.001) for each measure between those patients with a repeat length 27-35 versus those 36-39; as were total functional assessment, independence scale and total functional capacity (p < 0.001). Being aged 65 years or more (OR 5.81, 95 % CI 0.37-90.58, p = 0.02) and smoking (OR 13.99, 95 % CI 2.03-96.44, p = 0.007) were related to manifest HD in patients with CAG 36-39; those with an associated university degree or higher education were less frequently diagnosed as manifest HD (OR 0.10, 95 % CI 0.02-0.54, p = 0.007). Age, smoking and lower education achievement were found to be significantly associated with higher odds of manifest HD in patients with intermediate CAG repeat length mutations.
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SOX9 as a Predictor for Neurogenesis Potentiality of Amniotic Fluid Stem Cells.
Stem Cells Transl Med
PUBLISHED: 08-25-2014
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Preclinical studies of amniotic fluid-derived cell therapy have been successful in the research of neurodegenerative diseases, peripheral nerve injury, spinal cord injury, and brain ischemia. Transplantation of human amniotic fluid stem cells (AFSCs) into rat brain ventricles has shown improvement in symptoms of Parkinson's disease and also highlighted the minimal immune rejection risk of AFSCs, even between species. Although AFSCs appeared to be a promising resource for cell-based regenerative therapy, AFSCs contain a heterogeneous pool of distinct cell types, rendering each preparation of AFSCs unique. Identification of predictive markers for neuron-prone AFSCs is necessary before such stem cell-based therapeutics can become a reality. In an attempt to identify markers of AFSCs to predict their ability for neurogenesis, we performed a two-phase study. In the discovery phase of 23 AFSCs, we tested ZNF521/Zfp521, OCT6, SOX1, SOX2, SOX3, and SOX9 as predictive markers of AFSCs for neural differentiation. In the validation phase, the efficacy of these predictive markers was tested in independent sets of 18 AFSCs and 14 dental pulp stem cells (DPSCs). We found that high expression of SOX9 in AFSCs is associated with good neurogenetic ability, and these positive correlations were confirmed in independent sets of AFSCs and DPSCs. Furthermore, knockdown of SOX9 in AFSCs inhibited their neuronal differentiation. In conclusion, the discovery of SOX9 as a predictive marker for neuron-prone AFSCs could expedite the selection of useful clones for regenerative medicine, in particular, in neurological diseases and injuries.
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Genetic variants of CD209 associated with Kawasaki disease susceptibility.
PLoS ONE
PUBLISHED: 08-22-2014
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Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD.
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Comparison and validation of International Consensus Diagnostic Criteria for diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese cohort.
BMJ Open
PUBLISHED: 08-18-2014
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The International Consensus Diagnostic Criteria (ICDC) designed to diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The diagnostic performance of ICDC has not been previously evaluated in diffuse-type and focal-type AIP, respectively, in comparison with the revised HISORt and Asian criteria in Taiwan.
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Risk of tuberculosis among healthcare workers in an intermediate-burden country: A nationwide population study.
J. Infect.
PUBLISHED: 08-15-2014
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The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear.
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Association between recent use of proton pump inhibitors and nontyphoid salmonellosis: a nested case-control study.
Clin. Infect. Dis.
PUBLISHED: 08-04-2014
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The association between proton pump inhibitors (PPIs) and nontyphoid salmonellosis (NTS) continues to be debated. The current study was designed to determine the association between use of oral PPIs and the diagnosis of NTS.
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The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study.
BMC Med
PUBLISHED: 07-27-2014
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Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD.
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Levofloxacin-resistant haemophilus influenzae, Taiwan, 2004-2010.
Emerging Infect. Dis.
PUBLISHED: 07-26-2014
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Levofloxacin resistance in Haemophilus influenzae has increased significantly in Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular investigations of 182 levofloxacin-resistant isolates revealed that the increase was mainly the result of the spread of several clones in the elderly population in different regions.
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Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic dissemination of resistant and commensal bacteria through epithelial transcytosis.
Am. J. Physiol. Gastrointest. Liver Physiol.
PUBLISHED: 07-24-2014
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Antibiotic usage promotes intestinal colonization of antibiotic-resistant bacteria. However, whether resistant bacteria gain dominance in enteric microflora or disseminate to extraintestinal viscera remains unclear. Our aim was to investigate temporal diversity changes in microbiota and transepithelial routes of bacterial translocation after antibiotic-resistant enterobacterial colonization. Mice drinking water with or without antibiotics were intragastrically gavaged with ampicillin-resistant (Amp-r) nonpathogenic Escherichia coli (E. coli) and given normal water afterward. The composition and spatial distribution of intestinal bacteria were evaluated using 16S rDNA sequencing and fluorescence in situ hybridization. Bacterial endocytosis in epithelial cells was examined using gentamicin resistance assay and transmission electromicroscopy. Paracellular permeability was assessed by tight junctional immunostaining and measured by tissue conductance and luminal-to-serosal dextran fluxes. Our results showed that antibiotic treatment enabled intestinal colonization and transient dominance of orally acquired Amp-r E. coli in mice. The colonized Amp-r E. coli peaked on day 3 postinoculation and was competed out after 1 wk, as evidenced by the recovery of commensals, such as Escherichia, Bacteroides, Lachnospiraceae, Clostridium, and Lactobacillus. Mucosal penetration and extraintestinal dissemination of exogenous and endogenous enterobacteria were correlated with abnormal epithelial transcytosis but uncoupled with paracellular tight junctional damage. In conclusion, antibiotic-induced enteric dysbiosis predisposes to exogenous infection and causes systemic dissemination of both antibiotic-resistant and commensal enterobacteria through transcytotic routes across epithelial layers. These results may help explain the susceptibility to sepsis in antibiotic-resistant enteric bacterial infection.
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The subfamily-specific assembly of Eag and Erg K+ channels is determined by both the amino and the carboxyl recognition domains.
J. Biol. Chem.
PUBLISHED: 07-09-2014
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A functional voltage-gated K(+) (Kv) channel comprises four pore-forming ?-subunits, and only members of the same Kv channel subfamily may co-assemble to form heterotetramers. The ether-à-go-go family of Kv channels (KCNH) encompasses three distinct subfamilies: Eag (Kv10), Erg (Kv11), and Elk (Kv12). Members of different ether-à-go-go subfamilies, such as Eag and Erg, fail to form heterotetramers. Although a short stretch of amino acid sequences in the distal C-terminal section has been implicated in subfamily-specific subunit assembly, it remains unclear whether this region serves as the sole and/or principal subfamily recognition domain for Eag and Erg. Here we aim to ascertain the structural basis underlying the subfamily specificity of ether-à-go-go channels by generating various chimeric constructs between rat Eag1 and human Erg subunits. Biochemical and electrophysiological characterizations of the subunit interaction properties of a series of different chimeric and truncation constructs over the C terminus suggested that the putative C-terminal recognition domain is dispensable for subfamily-specific assembly. Further chimeric analyses over the N terminus revealed that the N-terminal region may also harbor a subfamily recognition domain. Importantly, exchanging either the N-terminal or the C-terminal domain alone led to a virtual loss of the intersubfamily assembly boundary. By contrast, simultaneously swapping both recognition domains resulted in a reversal of subfamily specificity. Our observations are consistent with the notion that both the N-terminal and the C-terminal recognition domains are required to sustain the subfamily-specific assembly of rat Eag1 and human Erg.
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Laparoscopic sleeve gastrectomy versus single anastomosis (mini-) gastric bypass for the treatment of type 2 diabetes mellitus: 5-year results of a randomized trial and study of incretin effect.
Obes Surg
PUBLISHED: 06-27-2014
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Bariatric surgery may be beneficial in mildly obese patients with poorly controlled diabetes. The optimal procedure to achieve diabetes remission is unknown. In 2011, we published the short-term results of a pilot study designed to evaluate the efficacy of diabetic control and the role of duodenal exclusion in mildly obese diabetic patients undergoing laparoscopic sleeve gastrectomy (SG) vs. a laparoscopic single anastomosis (mini-) gastric bypass (SAGB). This study analyzes the 5-year results and evaluates the incretin effect.
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Rapid identification of Acinetobacter baumannii, Acinetobacter nosocomialis and Acinetobacter pittii with a multiplex PCR assay.
J. Med. Microbiol.
PUBLISHED: 06-25-2014
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Acinetobacter baumannii, Acinetobacter nosocomialis and Acinetobacter pittii are clinically relevant members of the Acinetobacter calcoaceticus-A. baumannii (Acb) complex and important nosocomial pathogens. These three species are genetically closely related and phenotypically similar; however, they differ in their epidemiology, antibiotic resistance and pathogenicity. In this study, we investigated the use of a multiplex PCR-based assay designed to detect internal fragments of the 16S-23S rRNA intergenic region and the gyrB and recA genes. The assay was capable of differentiating A. baumannii, A. nosocomialis and A. pittii in a reliable manner. In 23 different reference strains and 89 clinical isolates of Acinetobacter species, the assay accurately identified clinically relevant Acb complex species except those 'between 1 and 3' or 'close to 13TU'. None of the non-Acb complex species was misidentified. In an analysis of 1034 positive blood cultures, the assay had a sensitivity of 92.4?% and specificity of 98.2?% for Acb complex identification. Our results show that a single multiplex PCR assay can reliably differentiate clinically relevant Acb complex species. Thus, this method may be used to better understand the clinical differences between infections caused by these species.
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While PAI-1 is independently associated with nonalcoholic fatty liver disease, leptin and adiponectin vary between genders.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-24-2014
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Alterations of adipocytokine levels and clinical parameters in nonalcoholic fatty liver disease (NAFLD) are crucial for the prognosis and complications of the diseases. However, the key adipocytokines independently associated with NAFLD have not been identified, and we aimed to investigate them.
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LGR5 regulates survival through mitochondria-mediated apoptosis and by targeting the Wnt/?-catenin signaling pathway in colorectal cancer cells.
Cell. Signal.
PUBLISHED: 06-13-2014
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Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a newly identified surface marker of colorectal cancer stem cells (CSCs). Expression level of LGR5 is commonly elevated in human CRCs. Our previous study demonstrated that the elevated expression of LGR5 is associated with CRC initiation and progression. However, the role of LGR5 in CRC pathogenesis has not been sufficiently established. In this study, we aimed to characterize the role of LGR5 in CRC pathogenesis using the loss-of-function approach. Depletion of LGR5 suppressed the growth of several cultured CRC cells and caused an increase in the fraction of apoptotic cells, which were analyzed using Annexin V/PI staining and DNA fragmentation assay. Furthermore, depleting LGR5 induced apoptosis through the loss of mitochondrial membrane potential. Additionally, depletion of LGR5 suppressed ?-catenin nuclear translocation and blocked the activity of Wnt/?-catenin signaling as manifested in the reduced expression of c-myc and cyclin D, two Wnt/?-catenin targets in CRC cells. Treatment with Wnt3a considerably alleviated the growth inhibition and apoptotic cell death induced by LGR5 depletion in CRC cells. These data suggested that LGR5 regulates cell proliferation and survival by targeting the Wnt/?-catenin signaling pathway. Thus, the findings of this study suggest that LGR5 plays a vital role in CRC pathogenesis and has the potential to serve as a diagnostic marker and a therapeutic target for CRC patients.
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Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.
PLoS Pathog.
PUBLISHED: 06-01-2014
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The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp) is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol)) also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol) enters the nucleus through the nuclear localization signal (NLS) and targets the pre-mRNA processing factor 8 (Prp8) to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol) associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol) complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.
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Recruitment and Screening for a Randomized Trial Investigating Roux-en-Y Gastric Bypass versus Intensive Medical Management for Treatment of Type 2 Diabetes.
Obes Surg
PUBLISHED: 05-28-2014
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Large-scale randomized clinical trials are needed to assess the role of Roux-en-Y gastric bypass (RYGB) in treating patients with type 2 diabetes mellitus (T2DM). Recruitment challenges must be understood.
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Discovery, structure-activity relationship studies, and anti-nociceptive effects of 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one as novel opioid receptor agonists.
Bioorg. Med. Chem.
PUBLISHED: 05-13-2014
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The ?-opioid receptor (MOR) is the major opioid receptor targeted by most analgesics in clinical use. However, the use of all known MOR agonists is associated with severe adverse effects. We reported that the 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-ones are novel opioid receptor agonists. Subsequent structural modification resulted in the potent MOR/KOR (?-opioid receptor) agonists 19, 20, and 21. Testing the analgesic effect of these in WT B6 mice (tail-flick test) gave ED50 values of 8.4, 10.9, and 26.6mg/kg, respectively. The 1-phenyl-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one core could be addressed in 1 or 2 synthetic steps with moderate to high percent of yield. In the adenylyl cyclase assay, compound 19 displayed a MOR/KOR agonist profile, with IC50 values of 0.73 and 0.41?M, respectively. Current results suggest that compound 19 is a promising lead to go further development and in vitro/in vivo adverse effects studies.
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Sheltering effect and indirect pathogenesis of carbapenem-resistant Acinetobacter baumannii in polymicrobial infection.
Antimicrob. Agents Chemother.
PUBLISHED: 05-05-2014
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The role of carbapenem-resistant Acinetobacter baumannii (CRAb) in polymicrobial infection remains elusive. Having observed the ability of CRAb to shelter other susceptible bacteria from carbapenem killing, we sought to determine the factors contributing to this sheltering effect by transforming different recombinant plasmids into recipient A. baumannii cells. The sheltering effects of CRAb were reproduced in recipient A. baumannii cells that highly expressed carbapenem-hydrolyzing class D ?-lactamases (CHDLs) through their associated strong promoter. With the use of Western blot analysis and a bioassay, the highly expressed CHDLs were found to be extracellularly released and led to hydrolysis of carbapenem. The level of extracellular CHDLs increased after challenge with a higher concentration of CHDL substrates, such as carbapenem and ticarcillin. This increased CHDL may, in part, be attributed to cell lysis, as indicated by the presence of extracellular gyrase. In the planktonic condition, the sheltering effect for the cocultured susceptible bacteria might represent an indirect and passive effect of the CRAb self-defense mechanism, because coculture with the susceptible pathogen did not augment the amount of the extracellular CHDLs. Polymicrobial infection caused by CRAb and a susceptible counterpart exerted higher pathogenicity than monomicrobial infection caused by either pathogen alone in mice receiving carbapenem therapy. This study demonstrated that CHDL-producing CRAb appears to provide a sheltering effect for carbapenem-susceptible pathogens via the extracellular release of CHDLs and, by this mechanism, can enhance the pathogenesis of polymicrobial infection in the presence of carbapenem therapy.
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Combining TNFSF15 and ASCA IgA can be used as a predictor for the stenosis/perforating phenotype of Crohn's disease.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-01-2014
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Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.
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CBB1003, a lysine-specific demethylase 1 inhibitor, suppresses colorectal cancer cells growth through down-regulation of leucine-rich repeat-containing G-protein-coupled receptor 5 expression.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 04-16-2014
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Lysine-specific demethylase 1 (LSD1) was highly expressed in several malignancies and had been implicated in pathological processes of cancer cells. However, the role of LSD1 in colorectal cancer (CRC) carcinogenesis, prognosis and treatment remains uncharacterized.
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Systemic approach to identify serum microRNAs as potential biomarkers for acute myocardial infarction.
Biomed Res Int
PUBLISHED: 04-14-2014
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Recent studies have revealed the role of microRNAs (miRNAs) in a variety of biological and pathological processes, including acute myocardial infarction (AMI). We hypothesized that ST-segment elevation myocardial infarction (STEMI) may be associated with an alteration of miRNAs and that circulating miRNAs may be used as diagnostic markers for STEMI.
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Effect of the use of low and high potency statins and sepsis outcomes.
Intensive Care Med
PUBLISHED: 04-13-2014
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Although statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users.
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A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.
ScientificWorldJournal
PUBLISHED: 04-07-2014
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Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.
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Surgical management in enterovesical fistula in crohn disease at a single medical center.
Int Surg
PUBLISHED: 03-28-2014
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Abstract Crohn disease is a chronic, transmural, inflammatory disease of the gastrointestinal tract with unknown etiology. It can affect any part of the gastrointestinal tract and may cause fistula, stricture, or abscess formation with disease progression. The preoperative diagnosis and definite management of this rare complication are challenges for physicians, urologists, and surgeons.
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Reduced Toll-like receptor 9 expression on peripheral CD14(+) monocytes of chronic hepatitis B patients and its restoration by effective therapy.
Antivir. Ther. (Lond.)
PUBLISHED: 03-14-2014
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Chronic hepatitis B (CHB) patients display Toll-like receptor 9 (TLR9)-dependent defective immune responses. We aimed to study TLR9 expression on CHB patients and its alteration during therapy.
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Genetic polymorphisms of ORAI1 and chronic kidney disease in Taiwanese population.
Biomed Res Int
PUBLISHED: 02-06-2014
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Taiwan has very high incidence and prevalence of chronic kidney disease (CKD), which easily progresses to end-stage renal disease (ESRD). The association between inflammation and CKD has been explored in several studies. ORAI1 functions as a pore-forming subunit of the store-operated calcium channels which are involved in the regulation of immune system. Hence, we conducted a case-control study to determine whether the genetic polymorphisms of ORAI1 gene is a susceptibility factor to CKD and its clinical features in a Taiwanese population. Five hundred seventy-nine CKD patients from a hospital-based CKD care program were included in the study. Five tagging single nucleotide polymorphisms (tSNPs) of ORAI1 were selected from the genotyping data of the Han Chinese population from the HapMap project. Among these polymorphisms, rs12313273 was found to be significantly associated with elevated serum calcium levels, which has been linked to increased risk of death in CKD patients. To have a better management of serum calcium, we suggest that ORAI1 polymorphisms might be used as a potential biomarker for initiating non-calcium-based phosphate binder in CKD patients in the future.
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The Epstein-Barr virus-encoded microRNA MiR-BART9 promotes tumor metastasis by targeting E-cadherin in nasopharyngeal carcinoma.
PLoS Pathog.
PUBLISHED: 02-01-2014
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MicroRNAs (miRNAs) are a family of small RNA molecules that negatively regulate the expression of protein-coding genes and play critical roles in orchestrating diverse cellular processes. This regulatory mechanism is also exploited by viruses to direct their life cycle and evade the host immune system. Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with multiple human diseases, including nasopharyngeal carcinoma (NPC), which is a highly metastatic type of tumor and is frequently reported in South Asia. Several viral proteins have been found to promote the migration and invasiveness of NPC cells. However, not all tumor tissues express these viral oncoproteins, suggesting that other mechanisms may contribute to the aggressive behavior of NPC tumor cells. A previous sequencing study by our group revealed that the EBV miRNA miR-BART9 was expressed at high levels in all EBV-positive NPC tissues. In the present study, we used gain- and loss-of-function approaches to investigate the effect of miR-BART9 in EBV-negative and EBV-positive NPC cells. We discovered that miR-BART9 promotes the migration and invasiveness of cultured NPC cells. The promigratory activity observed in vitro was manifested as an enhanced metastatic ability in vivo. Computational analysis revealed that miR-BART9 may target E-cadherin, a membrane protein that is pivotal in preserving cell-cell junctions and the epithelial phenotype. Through biochemical assays and functional rescue analysis, we confirmed that miR-BART9 specifically inhibits E-cadherin to induce a mesenchymal-like phenotype and promote the migration of NPC cells. These results indicated that miR-BART9 is a prometastatic viral miRNA and suggested that high levels of miR-BART9 in EBV-positive NPC cells may contribute to the aggressiveness of tumor cells.
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Iron Deficiency Anemia in Young Children with Predominant Breastfeeding.
Pediatr Neonatol
PUBLISHED: 01-23-2014
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Due to the increase of breastfeeding in infants, iron deficiency anemia (IDA) related to prolonged, predominant breastfeeding should be of concern. Mostly, the manifestation of IDA is indistinguishable and the enthusiastic advocacy of breastfeeding without concomitant education of complementary food may lead to ignorance of breast milk-related IDA, which may result in impaired psychomotor development of the baby. This retrospective study was conducted to re-emphasize this easily ignored but still prevalent illness.
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Unmet supportive care needs and characteristics of family caregivers of patients with oral cancer after surgery.
Psychooncology
PUBLISHED: 01-08-2014
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The aim of this study was to identify factors associated with unmet supportive care needs in family caregivers of patients with oral cancer after surgery.
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Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels.
Pancreatology
PUBLISHED: 01-07-2014
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To distinguish autoimmune pancreatitis (AIP), especially focal type, from pancreatic cancer, is a greatest challenge for clinician. The aim of the study is to compare the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of combined serum IgG4 and CA19-9 levels to differentiate AIP from pancreatic cancer by HISORt, Asian and international consensus diagnostic criteria.
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Risk factors and clinical outcome of sulbactam nonsusceptibility in monomicrobial Acinetobacter nosocomialis bacteremia.
J Microbiol Immunol Infect
PUBLISHED: 01-02-2014
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Sulbactam is an effective antimicrobial agent against multidrug-resistant Acinetobacter spp. This retrospective study evaluated the risk factors of sulbactam nonsusceptibility (SNS) in monomicrobial Acinetobacter nosocomialis bacteremia and its related outcome.
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Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: a population-based study.
Cancer
PUBLISHED: 01-02-2014
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Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with breast cancer. However, the clinical effect of TCM on survival, which is a major concern in these individuals, lacks evidence from large-scale clinical studies.
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Intramuscular Injection of AAV8 in Mice and Macaques Is Associated with Substantial Hepatic Targeting and Transgene Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Intramuscular (IM) administration of adeno-associated viral (AAV) vectors has entered the early stages of clinical development with some success, including the first approved gene therapy product in the West called Glybera. In preparation for broader clinical development of IM AAV vector gene therapy, we conducted detailed pre-clinical studies in mice and macaques evaluating aspects of delivery that could affect performance. We found that following IM administration of AAV8 vectors in mice, a portion of the vector reached the liver and hepatic gene expression contributed significantly to total expression of secreted transgenes. The contribution from liver could be controlled by altering injection volume and by the use of traditional (promoter) and non-traditional (tissue-specific microRNA target sites) expression control elements. Hepatic distribution of vector following IM injection was also noted in rhesus macaques. These pre-clinical data on AAV delivery should inform safe and efficient development of future AAV products.
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Distinct modes of transmission of tuberculosis in aboriginal and non-aboriginal populations in taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ?20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR)?=?5.98, p<0.0001). MTB lineages with high clustering were EAI (54.9%) among southern people, and Beijing (62.5%) and Haarlem (52.9%) among eastern aborigines. Resistance to first-line drugs and multidrug resistance (MDR) were significantly higher among eastern aborigines (?15%) than in any other geographic and ethnic group (p<0.05); MDR was detected in 5 of 28 eastern aboriginal patients ?20 years old. Among patients from the eastern region, clustered strains (p?=?0.01) and aboriginal ethnicity (p?=?0.04) were independent risk factors for MDR. The lifestyles of aborigines in eastern Taiwan may explain why the percentage of infected aborigines is much higher than for their Han Chinese counterparts. The significantly higher percentage of the MDR-MTB strains in the aboriginal population warrants close attention to control policy and vaccination strategy.
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Defects in the Acquisition of Tumor-Killing Capability of CD8+ Cytotoxic T Cells in Streptozotocin-Induced Diabetic Mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNF? assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNF? determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts.
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MicroRNAs MiR-218, MiR-125b, and Let-7g predict prognosis in patients with oral cavity squamous cell carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.
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SLCO3A1, a Novel Crohn's Disease-Associated Gene, Regulates NF-?B Activity and Associates with Intestinal Perforation.
PLoS ONE
PUBLISHED: 01-01-2014
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To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.
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The pattern of cytokine production in vitro induced by ancient and modern Beijing Mycobacterium tuberculosis strains.
PLoS ONE
PUBLISHED: 01-01-2014
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It is unclear to what extent the host-responses elicited by Beijing versus non-Beijing strains of Mycobacterium tuberculosis (MTB) contribute to the predominance of modern Beijing strains in Taiwan and some other Asian countries. The purpose of this study was to compare the expression profiles of virulence-related genes in human monocyte-derived macrophages infected in vitro with Beijing (ancient and modern strains) and non-Beijing strains (EAI strains) of MTB that are epidemic in Taiwan. We found that modern Beijing strains induced lower levels of pro-inflammatory cytokines, whereas EAI strains induced higher levels. Notably, the most prevalent modern Beijing sub-lineage, possessing intact RD150 and RD142 chromosomal regions, induced very low levels of pro-inflammatory cytokines, especially interleukin-1?. Moreover, in an intracellular growth assay, the survival of the same modern Beijing strain in human monocyte-derived macrophages was significantly higher than that of an ancient Beijing strain and an EAI strain. Taken together, these results may explain why modern Beijing strains of MTB predominate in Taiwan.
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Single-nucleotide polymorphism rs7251246 in ITPKC is associated with susceptibility and coronary artery lesions in Kawasaki disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Kawasaki disease (KD) is a multi-systemic vasculitis that preferentially affects children. A single nucleotide polymorphism (SNP) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) has been identified to be an important polymorphism in the risk of KD. This study was conducted to comprehensively investigate the associations between all tagging SNPs of ITPKC in the risk of KD in a Taiwanese population. A total of 950 subjects (381 KD patients and 569 controls) were recruited. Seven tagging SNPs (rs11673492, rs7257602, rs7251246, rs890934, rs10420685, rs2607420, rs2290692) were selected for TaqMan allelic discrimination assay. Clinical data of coronary artery lesions (CAL) and aneurysms were collected for analysis. A significant association was found between rs7251246 in ITPKC and CAL formation. Haplotype analysis for ITPKC polymorphisms also confirmed this association in the patients with CAL and aneurysm formation. This is the first study to identify that SNP rs7251246 in ITPKC is associated with the severity of KD.
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Single stock dynamics on high-frequency data: from a compressed coding perspective.
PLoS ONE
PUBLISHED: 01-01-2014
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High-frequency return, trading volume and transaction number are digitally coded via a nonparametric computing algorithm, called hierarchical factor segmentation (HFS), and then are coupled together to reveal a single stock dynamics without global state-space structural assumptions. The base-8 digital coding sequence, which is capable of revealing contrasting aggregation against sparsity of extreme events, is further compressed into a shortened sequence of state transitions. This compressed digital code sequence vividly demonstrates that the aggregation of large absolute returns is the primary driving force for stimulating both the aggregations of large trading volumes and transaction numbers. The state of system-wise synchrony is manifested with very frequent recurrence in the stock dynamics. And this data-driven dynamic mechanism is seen to correspondingly vary as the global market transiting in and out of contraction-expansion cycles. These results not only elaborate the stock dynamics of interest to a fuller extent, but also contradict some classical theories in finance. Overall this version of stock dynamics is potentially more coherent and realistic, especially when the current financial market is increasingly powered by high-frequency trading via computer algorithms, rather than by individual investors.
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Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice.
PLoS ONE
PUBLISHED: 01-01-2014
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SDF-1/CXCR4 signalling plays an important role in neuronal cell migration and brain development. However, the impact of CXCR4 deficiency in the postnatal mouse brain is still poorly understood. Here, we demonstrate the importance of CXCR4 on cerebellar development and motor behaviour by conditional inactivation of Cxcr4 in the central nervous system. We found CXCR4 plays a key role in cerebellar development. Its loss leads to defects in Purkinje cell dentritogenesis and axonal projection in vivo but not in cell culture. Transcriptome analysis revealed the most significantly affected pathways in the Cxcr4 deficient developing cerebellum are involved in extra cellular matrix receptor interactions and focal adhesion. Consistent with functional impairment of the cerebellum, Cxcr4 knockout mice have poor coordination and balance performance in skilled motor tests. Together, these results suggest ectopic the migration of granule cells impairs development of Purkinje cells, causes gross cerebellar anatomical disruption and leads to behavioural motor defects in Cxcr4 null mice.
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Folic acid supplementation in end-stage renal disease patients reduces total mortality rate.
J. Nephrol.
PUBLISHED: 12-05-2013
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Background: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular disease and elevated serum homocysteine levels. Although folic acid supplementation has been documented to reduce serum homocysteine levels in ESRD patients, most trials of folic acid therapy for reducing cardiovascular diseases in ESRD patients have failed, mainly because of limited patient numbers.?Methods: We used the Taiwan National Health Insurance Research Database (NHIRD) to conduct a matched-pair retrospective cohort study to clarify whether folic acid supplementation benefits ESRD patient survival. Patients were divided into a folic acid supplementation group and a control group. All-cause and cardiovascular-related mortality rates between groups were compared.?Results: In total, 55,636 stable incident hemodialysis patients were identified from the database. Using a propensity score-matched method and intention-to-treat analysis, the survival rate of 17,000 patients with folic acid supplementation was compared with a 1:1 matched control group. The baseline demographic data and comorbid disease incidence between the 2 groups were comparable. During the study period, the mortality rate in the matched pair cohort was 35.5% (n = 6,030) over a mean follow-up period of ?3.0 years, corresponding to a mortality rate of 12.8/100 patient-years. The all-cause mortality rates were 12.3 and 13.4/100 patient-years in the folic acid group and control group, respectively (p = 0.005). ?Conclusions: In adult hemodialysis patients, folic acid supplementation improves cardiovascular and all-cause mortality rates.
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Biodistribution of AAV8 Vectors Expressing Human Low-Density Lipoprotein Receptor in a Mouse Model of Homozygous Familial Hypercholesterolemia.
Hum Gene Ther Clin Dev
PUBLISHED: 11-09-2013
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Abstract Recombinant adeno-associated viral vectors based on serotype 8 (AAV8) transduce liver with superior tropism following intravenous (IV) administration. Previous studies conducted by our lab demonstrated that AAV8-mediated transfer of the human low-density lipoprotein receptor (LDLR) gene driven by a strong liver-specific promoter (thyroxin-binding globulin [TBG]) leads to high level and persistent gene expression in the liver. The approach proved efficacious in reducing plasma cholesterol levels and resulted in the regression of atherosclerotic lesions in a murine model of homozygous familial hypercholesterolemia (hoFH). Prior to advancing this vector, called AAV8.TBG.hLDLR, to the clinic, we set out to investigate vector biodistribution in an hoFH mouse model following IV vector administration to assess the safety profile of this investigational agent. Although AAV genomes were present in all organs at all time points tested (up to 180 days), vector genomes were sequestered mainly in the liver, which contained levels of vector 3 logs higher than that found in other organs. In both sexes, the level of AAV genomes gradually declined and appeared to stabilize 90 days post vector administration in most organs although vector genomes remained high in liver. Vector loads in the circulating blood were high and close to those in liver at the early time point (day 3) but rapidly decreased to a level close to the limit of quantification of the assay. The results of this vector biodistribution study further support a proposed clinical trial to evaluate AAV8 gene therapy for hoFH patients.
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Association between recent use of fluoroquinolones and rhegmatogenous retinal detachment: a population-based cohort study.
Clin. Infect. Dis.
PUBLISHED: 10-28-2013
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Background.?An association between use of oral fluoroquinolones (FQs) and retinal detachment remains controversial. This study was to determine the association of recent use of oral FQs and rhegmatogenous retinal detachment (RRD) after adjustment for confounding factors known to be associated with RRD. Methods.?This retrospective population-based cohort study with parallel groups included adults treated with an oral FQ (FQ cohort = 178 179 prescriptions) and propensity score-matched adults treated with oral amoxicillin (amoxicillin cohort = 178 179 prescriptions). The data were extracted from the Taiwan National Health Insurance Research Database from 1998 to 2010. Interaction terms were used to identify populations at risk. RRD was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results.?During the 90-day follow-up period, 96 patients (0.054%) in the FQ cohort developed RRD compared to 46 (0.026%) among the matched amoxicillin cohort. The overall adjusted hazard ratio (HR) for FQ use and RRD was 2.07 (95% confidence interval [CI], 1.45-2.96). The interval between use of oral FQs and onset of RRD was 35.5 days (interquartile range, 14-57 days). Interaction terms were not significant for age, sex, diabetes, indications for antimicrobials, or underlying ophthalmic conditions. The adjusted HRs differed for specific FQs. These were 10.68 (95% CI, 3.28-34.82) for ciprofloxacin, 2.41 (95% CI, .76-7.68) for levofloxacin, 2.00 (95% CI, 1.06-3.79) for norfloxacin, and 1.17 (95% CI, .59-2.31) for ofloxacin. Conclusions.?The use of oral FQs was associated with the subsequent occurrence of RRD. The FQ risk was independent of age, sex, diabetes, indications for antimicrobials, and underlying ophthalmic conditions. Certain FQs carried higher risk of RRD.
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Molecular epidemiology of Mycobacterium tuberculosis in aboriginal peoples of Taiwan, 2006-2011.
J. Infect.
PUBLISHED: 10-07-2013
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Previous research revealed a 6-fold higher incidence of tuberculosis (TB) amongst aborigines compared to Han Chinese in Taiwan. To investigate the reasons for this disparity, we genotyped Mycobacterium tuberculosis (MTB) strains obtained from members of different aboriginal tribes in different geographical regions of Taiwan by using molecular methods. In total, 177 isolates of MTB collected from patients at four hospitals in Taiwan from January 2006 to December 2011 were analysed by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem-repeat (MIRU-VNTR) typing. The most prevalent strains in the eastern and central regions of Taiwan were Beijing (45.7% in eastern) and Haarlem (39.1% in eastern, 37.1% in central) lineages, whereas in southern regions the most prevalent strains were EAI (47.7%) and Haarlem (20.5%) lineages. The high prevalence of EAI in southern Taiwan aborigines may be closely associated with Austronesian culture. This study provides a first overview of the M. tuberculosis strains circulating in aboriginal populations in Taiwan. The high prevalences of certain MTB lineages within aboriginal sub-populations suggest that transmission of MTB may have been restricted to close contacts.
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Change of glycaemic control and predictors in diabetes patients: longitudinal observational study during the one year after hospital discharge.
Int J Nurs Pract
PUBLISHED: 10-05-2013
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Glycated haemoglobin (HbA1c) might reflect glycaemic control in persons with diabetes. Study aims were to identify changes in glycated haemoglobin values and predictors (baseline coping behaviour, fasting plasma glucose, disease-related and demographic factors) in patients during 1 year after hospital discharge. A longitudinal prospective design with convenience sampling was used. Subjects were recruited from a community hospital in Taiwan. Measures included Jalowiec Coping Scale, fasting plasma glucose, HbA1c values, and demographics. Generalized estimating equation was used to determine factors of change in glycated haemoglobin. A total of 57 patients completed 1 year of follow-up. Half did not receive diabetes mellitus education and regular exercise. Patients glycated haemoglobin levels follow controls at 6 months after discharge. Patients with higher levels of blood glucose, less problem-focused coping and greater emotion-focused coping were associated with poor glycaemic control. Education programmes should involve individual-centred care and health behaviours for prevention of diabetes complications.
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Depression and predictors in Taiwanese survivors with oral cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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Depression is a comorbid disabling problem and potentially affects patient likelihood of survival. The aims of this study were to recognize the characteristics of depression and investigate associated predictor factors in patients with oral cancers.
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Prenatal hypoxia downregulates the expression of pulmonary vascular endothelial growth factor and its receptors in fetal mice.
Neonatology
PUBLISHED: 09-13-2013
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Previous reports showed that prenatal hypoxia delays the process of lung maturation. Vascular endothelial growth factor (VEGF) and its receptors were important for lung development. However, the role of VEGF and VEGF receptors in altered fetal lung development and maturation induced by prenatal hypoxia remains unknown.
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A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan.
BMC Gastroenterol
PUBLISHED: 08-01-2013
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The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohns disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan.
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Enhancing the utility of adeno-associated virus gene transfer through inducible tissue-specific expression.
Hum Gene Ther Methods
PUBLISHED: 07-31-2013
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The ability to regulate both the timing and specificity of gene expression mediated by viral vectors will be important in maximizing its utility. We describe the development of an adeno-associated virus (AAV)-based vector with tissue-specific gene regulation, using the ARGENT dimerizer-inducible system. This two-vector system based on AAV serotype 9 consists of one vector encoding a combination of reporter genes from which expression is directed by a ubiquitous, inducible promoter and a second vector encoding transcription factor domains under the control of either a heart- or liver-specific promoter, which are activated with a small molecule. Administration of the vectors via either systemic or intrapericardial injection demonstrated that the vector system is capable of mediating gene expression that is tissue specific, regulatable, and reproducible over induction cycles. Somatic gene transfer in vivo is being considered in therapeutic applications, although its most substantial value will be in basic applications such as target validation and development of animal models.
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Incidence and outcome of newly-diagnosed tuberculosis in schizophrenics: a 12-year, nationwide, retrospective longitudinal study.
BMC Infect. Dis.
PUBLISHED: 07-27-2013
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To control tuberculosis (TB), it is critical to identify at risk populations. Schizophrenia is recognized as an important risk factor for TB. However, previous studies have been confounded by comorbidities, and reports of TB infection outcomes are rare. Therefore, the current nation-wide study aimed to compare the adjusted incidence and outcome of TB diseases in schizophrenics and the general population.
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Lgr5 promotes cancer stemness and confers chemoresistance through ABCB1 in colorectal cancer.
Biomed. Pharmacother.
PUBLISHED: 07-25-2013
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Chemotherapy failure is a major problem in patients with advanced colorectal carcinoma (CRC). Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a well-established target gene of the Wnt pathway and is a bona fide marker of CRC cancer stem cells (CSCs). Our previous study showed that CRC patients with higher Lgr5 level are associated with poor response to 5-fluoracil-based treatment. In this study, we investigated the mechanisms underlying Lgr5-associated chemoresistance in cancer stem cells derived from cultured CRC cells.
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Comparison between bacteremia caused by carbapenem resistant Acinetobacter baumannii and Acinetobacter nosocomialis.
BMC Infect. Dis.
PUBLISHED: 07-08-2013
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It is unknown whether there are differences between bacteremia caused by carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Acinetobacter nosocomialis (CRAN). This study aims to investigate the differences, especially in clinical outcomes, between patients with bacteremia caused by CRAB or CRAN.
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Juvenile Myelomonocytic Leukemia in a Premature Neonate Mimicking Neonatal Sepsis.
Pediatr Neonatol
PUBLISHED: 06-01-2013
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Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Its presentations include anemia, thrombocytopenia, monocytosis, skin rash, marked hepatomegaly, and/or splenomegaly. Fever and respiratory involvement are common. Here, we report a case of a premature neonate with initial symptoms of respiratory distress. She gradually developed clinical manifestations of JMML that mimicked neonatal sepsis. Three weeks after birth, JMML was diagnosed. This is the first reported case of JMML presenting in a premature infant in Taiwan.
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Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer.
Int J Colorectal Dis
PUBLISHED: 05-21-2013
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The leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is an adult intestinal stem cell marker frequently detected in human colorectal cancers (CRCs). However, the value of Lgr5 level in CRC prognosis and treatment prediction has not been well characterized.
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The chemical chaperon 4-phenylbutyric acid ameliorates hepatic steatosis through inhibition of de novo lipogenesis in high-fructose-fed rats.
Int. J. Mol. Med.
PUBLISHED: 05-16-2013
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Non-alcoholic fatty liver disease caused by dietary factors such as a high fructose intake is a growing global concern. The aim of this study was to investigate the intervention effects of an endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (PBA) on liver steatosis induced by high-fructose feeding in rats and the possible underlying mechanisms. Wistar rats were divided into the control, high-fructose group (HFru) and PBA intervention (HFru-PBA) groups. PBA intervention was initiated following 4 weeks of high-fructose feeding. After 8 weeks of feeding, the ERS markers p-PERK, p-eIF2?, p-IRE-1, spliced XBP-1, ATF-6 were measured by western blotting. Liver triglyceride contents and morphological changes were examined. The protein expression of lipogenic key enzymes (ACC, FAS and SCD-1) and upstream transcriptional factors (SREBP-1c and ChREBP) were measured. The ERS-related cell events, oxidative stress and apoptosis, were evaluated by standard methods. Results demonstrated that PBA intervention significantly resolved hepatic ERS and improved liver steatosis induced by high-fructose feeding in rats. The protein expression of ACC, FAS, SCD-1 and SREBP-1c was upregulated in high-fructose-fed rats, whereas it decreased following PBA intervention. Oxidative stress and apoptosis were observed in livers of high-fructose-fed rats, but were alleviated by PBA intervention. ERS is involved in the development of fatty liver induced by a high fructose intake. ERS inhibition by PBA can therefore ameliorate liver steatosis through inhibition of hepatic lipogenesis.
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Risk factors of community-onset urinary tract infections caused by plasmid-mediated AmpC ?-lactamase-producing Enterobacteriaceae.
J Microbiol Immunol Infect
PUBLISHED: 04-30-2013
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The AmpC ?-lactamase (AmpC)-producing Enterobacteriaceae emerged worldwide. This study was conducted to determine the risk factors of community-onset urinary tract infections (UTIs) caused by plasmid-mediated AmpC-producing Enterobacteriaceae.
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Evolution of carbapenem resistance in Acinetobacter baumannii: An 18-year longitudinal study from a medical center in northern Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 04-30-2013
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Carbapenem-resistant Acinetobacter baumannii has emerged as an important cause of nosocomial infections with high morbidity and mortality. The carbapenemases, especially class D carbapenem-hydrolyzing oxacillinases (CHDLs), play an important role, but the relationship between their prevalence trend and carbapenem resistance remains unclear.
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Epidemiology and risk factors of community-onset urinary tract infection caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae in a medical center in Taiwan: A prospective cohort study.
J Microbiol Immunol Infect
PUBLISHED: 04-25-2013
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Extended-spectrum ?-lactamase (ESBL)-producing pathogens have been increasingly identified in community-onset urinary tract infection (UTI). This study was conducted to determine the epidemiology and risk factors of community-onset UTI caused by ESBL-producing pathogens, and to determine the correlation of antimicrobial resistance with ESBL detected by phenotypic and genotypic methods.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.