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Find video protocols related to scientific articles indexed in Pubmed.
Structural basis and distal effects of Gag substrate coevolution in drug resistance to HIV-1 protease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-29-2014
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Drug resistance mutations in response to HIV-1 protease inhibitors are selected not only in the drug target but elsewhere in the viral genome, especially at the protease cleavage sites in the precursor protein Gag. To understand the molecular basis of this protease-substrate coevolution, we solved the crystal structures of drug resistant I50V/A71V HIV-1 protease with p1-p6 substrates bearing coevolved mutations. Analyses of the protease-substrate interactions reveal that compensatory coevolved mutations in the substrate do not restore interactions lost due to protease mutations, but instead establish other interactions that are not restricted to the site of mutation. Mutation of a substrate residue has distal effects on other residues' interactions as well, including through the induction of a conformational change in the protease. Additionally, molecular dynamics simulations suggest that restoration of active site dynamics is an additional constraint in the selection of coevolved mutations. Hence, protease-substrate coevolution permits mutational, structural, and dynamic changes via molecular mechanisms that involve distal effects contributing to drug resistance.
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CCAAT-Enhancer-Binding Protein Homologous Protein Deficiency Attenuates Oxidative Stress and Renal Ischemia-Reperfusion Injury.
Antioxid. Redox Signal.
PUBLISHED: 10-17-2014
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Abstract Aims: Renal ischemia-reperfusion (I/R) is a major cause of acute renal failure. The mechanisms of I/R injury include endoplasmic reticulum (ER) stress, inflammatory responses, hypoxia, and generation of reactive oxygen species (ROS). CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is involved in the ER stress signaling pathways. CHOP is a transcription factor and a major mediator of ER stress-induced apoptosis. However, the role of CHOP in renal I/R injury is still undefined. Here, we investigated whether CHOP could regulate I/R-induced renal injury using CHOP-knockout mice and cultured renal tubular cells as models. Results: In CHOP-knockout mice, loss of renal function induced by I/R was prevented. Renal proximal tubule damage was induced by I/R in wild-type mice; however, the degree of alteration was significantly less in CHOP-knockout mice. CHOP deficiency also decreased the I/R-induced activation of caspase-3 and -8, apoptosis, and lipid peroxidation, whereas the activity of endogenous antioxidants increased. In an in vitro I/R model, small interfering RNA targeting CHOP significantly reversed increases in H2O2 formation, inflammatory signals, and apoptotic signals, while enhancing the activity of endogenous antioxidants in renal tubular cells. Innovation: To the best of our knowledge, this is the first study which demonstrates that CHOP deficiency attenuates oxidative stress and I/R-induced acute renal injury both in vitro and in vivo. Conclusion: These findings suggest that CHOP regulates not only apoptosis-related signaling but also ROS formation and inflammation in renal tubular cells during I/R. CHOP may play an important role in the pathophysiology of I/R-induced renal injury. Antioxid. Redox Signal. 00, 000-000.
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Down-regulation of Slit-Robo Pathway Mediating Neuronal Cytoskeletal Remodeling Processes Facilitates the Antidepressive-like Activity of Gastrodia elata Blume.
J. Agric. Food Chem.
PUBLISHED: 10-16-2014
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Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved depressive-like behavior by influencing neurotransmitters in rats subjected to the forced swimming test. To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes. Although Slit-Robo signaling has been well investigated in neuronal development, its relationship with depression is not fully understood. We provide a potential hint on the mechanism responsible for the antidepressive-like activity of WGE. In conclusion, we suggest that the Slit-Robo pathway and neuronal cytoskeleton remodeling are possibly one of the pathways associated with the antidepressive-like effects of WGE.
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Potential advantages of Chinese medicine Taohong Siwu Decoction () combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats.
Chin J Integr Med
PUBLISHED: 09-24-2014
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To investigate whether combination treatment with Taohong Siwu Decoction (, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model.
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Comparison of cardiovascular co-morbidities and CPAP use in patients with positional and non-positional mild obstructive sleep apnea.
BMC Pulm Med
PUBLISHED: 09-23-2014
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This retrospective cohort study aimed to determine if there are differences in cardiovascular co-morbidities, blood pressure (BP) and continuous positive airway pressure (CPAP) use between patients with positional-dependent and nonpositional-dependent obstructive sleep apnea (OSA).
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Endovascular intervention in Taiwanese patients with critical limb ischemia: patient outcomes in 333 consecutive limb procedures with a 3-year follow-up.
J. Formos. Med. Assoc.
PUBLISHED: 09-22-2014
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Midterm outcomes of endovascular intervention (EVI) for critical limb ischemia (CLI) have not been previously reported in Taiwan. This study assessed the safety, feasibility, and patient-oriented outcomes for CLI patients after EVI.
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Multidisciplinary Care Program for Advanced Chronic Kidney Disease: Reduces Renal Replacement and Medical Costs.
Am. J. Med.
PUBLISHED: 08-19-2014
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Multidisciplinary care is advocated as an effective chronic kidney disease treatment program in a few, but not all studies. Our study aimed to evaluate the effect of multidisciplinary care on renal outcome and patient survival using a larger cohort.
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Increased risk of end-stage renal disease in patients with renal cell carcinoma: a 12-year nationwide follow-up study.
Medicine (Baltimore)
PUBLISHED: 08-15-2014
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The effect of renal cell carcinoma (RCC) on the risk for end-stage renal disease (ESRD) has not been confirmed. The present population-based study used the claims data from the Taiwan National Health Institutes from 1998 to 2010 to compare the risk for ESRD in patients with and without RCC.The study cohort consisted of 2940 patients who had newly diagnosed with RCC but no history of ESRD; the control cohort consisted of 23,520 matched patients without RCC. Cox proportional hazard regressions were performed to compute ESRD risk after adjusting for possible confounding factors. Kaplan-Meier analysis and the log-rank test were also used to compare patients and controls.A total of 119 patients in the RCC group (incidence rate: 119/2940; 4.05%) and 160 patients in the control group (incidence rate: 160/23,520; 0.68%) were diagnosed with ESRD during the follow-up period. After adjusting for potential confounders, the RCC group had an ESRD hazard ratio (HR) of 5.63 [95% confidence interval (CI): 4.37-7.24] relative to the control group. In addition, among patients with RCC, females (adjusted HR: 6.95, 95% CI: 4.82-10.1) had a higher risk for ESRD than males (adjusted HR: 4.79, 95% CI: 3.37-6.82). Finally, there were significant joint effects of chronic kidney disease and diabetes on increasing the risk of ESRD in patients with and without RCC (P?
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Integrating team resource management program into staff training improves staff's perception and patient safety in organ procurement and transplantation: the experience in a university-affiliated medical center in Taiwan.
BMC Surg
PUBLISHED: 08-11-2014
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The process involved in organ procurement and transplantation is very complex that requires multidisciplinary coordination and teamwork. To prevent error during the processes, teamwork education and training might play an important role. We wished to evaluate the efficacy of implementing a Team Resource Management (TRM) program on patient safety and the behaviors of the team members involving in the process.
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Observation of the rose petal effect over single- and dual-scale roughness surfaces.
Nanotechnology
PUBLISHED: 08-06-2014
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Rose petals exhibit superhydrophobicity with strong adhesion to pin water drops, known as the 'petal effect.' It is generally believed that the petal effect is attributed to dual-scale roughness, that is, the surface possesses both a nanostructure and a microstructure (Feng et al 2008 Langmuir 24 4114). In this study, we demonstrate that the dual-scale roughness is not a necessary condition for a surface of the petal effect. A surface of single-scale roughness, either at the nanoscale or the microscale alone, within a certain roughness region may also exhibit the petal effect. The surface roughness plays the essential role on the wetting behavior and governs the contact angle in the Wenzel or Cassie state, as well as the contact angle hysteresis. A water drop on the surface of the petal effect under the condition of the advancing and receding contact angle would fall into, respectively, the Cassie and Wenzel state, which leads to a contact angle hysteresis large enough to pin the water drop. On both single and dual textured hydrophobic surfaces, a sequence of wetting transitions: Wenzel state ? petal state (sticky superhydrophobic state) ? lotus state (slippery superhydrophobic state) is consistently observed by simply increasing the surface roughness.
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Time to have a paradigm shift in health care quality measurement.
J. Formos. Med. Assoc.
PUBLISHED: 08-05-2014
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Quality measurement is important to stakeholders in providing valid information for improvement, and has been associated with hospital accreditation in most countries. The commonly used categories of indicators are structure, process, and outcome. Outcome indicators are of foremost importance as they reflect the effect of health care; structure indicators are commonly used for assessing capacities or facilities available for providing services, whereas process indicators assess how well the service is delivered, and provide essential and important information for quality improvement. For a process indicator to be valid, it should be linked to an outcome, whereas a structure indicator must be linked to a better outcome. Although there are no strict rules for usage or selection of indicators, it is important to ensure adequate coverage of relevant domains of the health care services intended to be evaluated. Because the trends in health care services and management are changing, it is time to have a paradigm shift in health care quality measurement. Although evaluating the quality had also been extended to include quality of life and patient satisfaction, the ultimate aim of health care services should be "staying healthy, getting healthy, and living healthy". It is important for physicians to learn how to use these clinical indicators for improving service performance and organizational growth.
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Multiple complexes of long aliphatic N-acyltransferases lead to synthesis of 2,6-diacylated/2-acyl-substituted glycopeptide antibiotics, effectively killing vancomycin-resistant enterococcus.
J. Am. Chem. Soc.
PUBLISHED: 07-25-2014
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Teicoplanin A2-2 (Tei)/A40926 is the last-line antibiotic to treat multidrug-resistant Gram-positive bacterial infections, e.g., methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). This class of antibiotics is powered by the N-acyltransferase (NAT) Orf11*/Dbv8 through N-acylation on glucosamine at the central residue of Tei/A40926 pseudoaglycone. The NAT enzyme possesses enormous value in untapped applications; its advanced development is hampered largely due to a lack of structural information. In this report, we present eight high-resolution X-ray crystallographic unary, binary, and ternary complexes in order to decipher the molecular basis for NAT's functionality. The enzyme undergoes a multistage conformational change upon binding of acyl-CoA, thus allowing the uploading of Tei pseudoaglycone to enable the acyl-transfer reaction to take place in the occlusion between the N- and C-halves of the protein. The acyl moiety of acyl-CoA can be bulky or lengthy, allowing a large extent of diversity in new derivatives that can be formed upon its transfer. Vancomycin/synthetic acyl-N-acetyl cysteamine was not expected to be able to serve as a surrogate for an acyl acceptor/donor, respectively. Most strikingly, NAT can catalyze formation of 2-N,6-O-diacylated or C6?C2 acyl-substituted Tei analogues through an unusual 1,4-migration mechanism under stoichiometric/solvational reaction control, wherein selected representatives showed excellent biological activities, effectively counteracting major types (VanABC) of VRE.
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Andrographolide induces vascular smooth muscle cell apoptosis through a SHP-1-PP2A-p38MAPK-p53 cascade.
Sci Rep
PUBLISHED: 06-24-2014
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The abnormal growth of vascular smooth muscle cells (VSMCs) is considered a critical pathogenic process in inflammatory vascular diseases. We have previously demonstrated that protein phosphatase 2 A (PP2A)-mediated NF-?B dephosphorylation contributes to the anti-inflammatory properties of andrographolide, a novel NF-?B inhibitor. In this study, we investigated whether andrographolide causes apoptosis, and characterized its apoptotic mechanisms in rat VSMCs. Andrographolide activated the p38 mitogen-activated protein kinase (p38MAPK), leading to p53 phosphorylation. Phosphorylated p53 subsequently transactivated the expression of Bax, a pro-apoptotic protein. Transfection with pp2a small interfering RNA (siRNA) suppressed andrographolide-induced p38MAPK activation, p53 phosphorylation, and caspase 3 activation. Andrographolide also activated the Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), and induced PP2A dephosphorylation, both of which were inhibited by the SHP-1 inhibitor sodium stibogluconate (SSG) or shp-1 siRNA. SSG or shp-1 siRNA prevented andrographolide-induced apoptosis. These results suggest that andrographolide activates the PP2A-p38MAPK-p53-Bax cascade, causing mitochondrial dysfunction and VSMC death through an SHP-1-dependent mechanism.
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Calreticulin Regulates VEGF-A in Neuroblastoma Cells.
Mol. Neurobiol.
PUBLISHED: 06-18-2014
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Calreticulin (CRT) has been previously correlated with the differentiation of neuroblastoma (NB), implying a favorable prognostic factor. Vascular endothelial growth factor (VEGF) has been reported to participate in the behavior of NB. This study investigated the association of CRT and VEGF-A in NB cells. The expressions of VEGF-A and HIF-1?, with overexpression or knockdown of CRT, were measured in three NB cells (SH-SY5Y, SK-N-DZ, and stNB-V1). An inducible CRT NB cell line and knockdown CRT stable cell lines were also established. The impacts of CRT overexpression on NB cell apoptosis, proliferation, and differentiation were also evaluated. We further examined the role of VEGF-A in the NB cell differentiation via VEGF receptor blockade. Constitutive overexpression of CRT led to NB cell differentiation without proliferation. Thus, an inducible CRT stNB-V1 cell line was generated by a tetracycline-regulated gene system. CRT overexpression increased VEGF-A and HIF-1? messenger RNA (mRNA) expressions in SH-SY5Y, SK-N-DZ, and stNB-V1 cells. CRT overexpression also enhanced VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. Knockdown of CRT decreased VEGF-A and HIF-1? mRNA expressions and lowered VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. We further demonstrated that NB cell apoptosis was not affected by CRT overexpression in stNB-V1 cells. Nevertheless, overexpression of CRT suppressed cell proliferation and enhanced cell differentiation in stNB-V1 cells, whereas blockage of VEGFR-1 markedly suppressed the expression of neuron-specific markers including GAP43, NSE2, and NFH, as well as TrkA, a molecular marker indicative of NB cell differentiation. Our findings suggest that VEGF-A is involved in CRT-related neuronal differentiation in NB. Our work may provide important information for developing a new therapeutic strategy to improve the outcome of NB patients.
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SeqSIMLA2: Simulating Correlated Quantitative Traits Accounting for Shared Environmental Effects in User-Specified Pedigree Structure.
Genet. Epidemiol.
PUBLISHED: 06-15-2014
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Simulation tools that simulate sequence data in unrelated cases and controls or in families with quantitative traits or disease status are important for genetic studies. The simulation tools can be used to evaluate the statistical power for detecting the causal variants when planning a genetic epidemiology study, or to evaluate the statistical properties for new methods. We previously developed SeqSIMLA version 1 (SeqSIMLA1), which simulates family or case-control data with a disease or quantitative trait model. SeqSIMLA1, and several other tools that simulate quantitative traits, do not specifically model the shared environmental effects among relatives on a trait. However, shared environmental effects are commonly observed for some traits in families, such as body mass index. SeqSIMLA1 simulates a fixed three-generation family structure. However, it would be ideal to simulate prespecified pedigree structures for studies involving large pedigrees. Thus, we extended SeqSIMLA1 to create SeqSIMLA2, which can simulate correlated traits and considers the shared environmental effects. SeqSIMLA2 can also simulate prespecified large pedigree structures. There are no restrictions on the number of individuals that can be simulated in a pedigree. We used a blood pressure example to demonstrate that SeqSIMLA2 can simulate realistic correlation structures between the systolic and diastolic blood pressure among relatives. We also showed that SeqSIMLA2 can simulate large pedigrees with large chromosomal regions in a reasonable time frame.
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Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver disease through modulation of lipid metabolism and oxidative stress.
J. Agric. Food Chem.
PUBLISHED: 06-11-2014
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This study investigated the protective properties of garlic essential oil (GEO) and its major organosulfur component (diallyl disulfide, DADS) against the development of nonalcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a normal or high-fat diet (HFD) with/without GEO (25, 50, and 100 mg/kg) or DADS (10 and 20 mg/kg) for 12 weeks. GEO and DADS dose-dependently exerted antiobesity and antihyperlipidemic effects by reducing HFD-induced body weight gain, adipose tissue weight, and serum biochemical parameters. Administration of 50 and 100 mg/kg GEO and 20 mg/kg DADS significantly decreased the release of pro-inflammatory cytokines in liver, accompanied by elevated antioxidant capacity via inhibition of cytochrome P450 2E1 expression during NAFLD development. The anti-NAFLD effects of GEO and DADS were mediated through down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as stimulation of peroxisome proliferator-activated receptor ? and carnitine palmitoyltransferase-1. These results demonstrate that GEO and DADS dose-dependently protected obese mice with long-term HFD-induced NAFLD from lipid accumulation, inflammation, and oxidative damage by ameliorating lipid metabolic disorders and oxidative stress. The dose of 20 mg/kg DADS was equally as effective in preventing NAFLD as 50 mg/kg GEO containing the same amount of DADS, which demonstrates that DADS may be the main bioactive component in GEO.
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Diagnostic performance of random urine samples using albumin concentration vs ratio of albumin to creatinine for microalbuminuria screening in patients with diabetes mellitus: a systematic review and meta-analysis.
JAMA Intern Med
PUBLISHED: 05-07-2014
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A random urine sample measuring the albumin concentration (UAC) without simultaneously measuring the urinary creatinine is less expensive than measuring the ratio of albumin to creatinine (ACR), but comparisons of their diagnostic performance for microalbuminuria screening among patients with diabetes mellitus (DM) have not been undertaken in previous meta-analyses.
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A full-duplex lightwave transmission system with an innovative VCSEL-based PM-to-IM converter.
Opt Express
PUBLISHED: 05-03-2014
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A full-duplex lightwave transmission system employing innovative VCSEL-based PM-to-IM converters to deliver intensity-modulated CATV/phase-modulated RoF/intensity-remodulated RoF signals over two 40-km SMFs links is proposed and demonstrated. To be the first one of employing VCSEL-based PM-to-IM converters in full-duplex lightwave transmission systems, the downstream light is successfully intensity-remodulated with RoF signal for up-link transmission. Good performances of CNR/CSO/CTB are achieved for downstream CATV signal transmission, and low BER values are obtained for both downstream and upstream RoF signals transmissions. Our proposed systems present brilliant performances in delivering hybrid CATV and RoF signals. Such a full-duplex lightwave transmission system would be very attractive for fiber trunk applications to provide broadband integrated services.
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Multidrug resistance protein 4 (MRP4/ABCC4) regulates thrombus formation in vitro and in vivo.
Eur. J. Pharmacol.
PUBLISHED: 04-23-2014
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The multidrug resistance protein 4 (MRP4) is a member of the ABCC subfamily of the adenosine triphosphate-binding cassette transporters that remove cyclic nucleotides from platelets and uptake ADP into dense granule in platelets. However, whether MRP4 directly involves platelet activation remains unclear. Thus, the aim of our study was to determine the detailed mechanisms underlying the regulation of MRP4 in platelet activation. Our results revealed that the MRP4 inhibitor MK571 inhibited collagen-induced platelet aggregation which was partially reversed by the PKA inhibitor H89, but not by the adenylyl cyclase (AC) inhibitor SQ22536 and the guanylyl cyclase (GC) inhibitor ODQ, suggesting that MK571 can prevent collagen-induced aggregation via a route independent of cyclic nucleotide production. In the present study, we found that MK571 inhibited collagen-induced ATP release and calcium mobilization. The phosphorylation of protein kinase C, JNK, and Akt was also inhibited by MK571, and electron spin resonance experiment showed that MK571 significantly reduced hydroxyl radical formation. Moreover, MK571 delayed platelet plug formation in vitro by a PFA-100 device, and delayed thrombus formation in mesenteric venules of mice irradiated by fluorescein sodium. However, previous studies have reported that MK571 also blocks MRP1 and leukotriene D4 (LTD4) receptor. Therefore, whether MK571 inhibits platelet activation through MRP1 or LTD4 receptor needs to be considered and further defined. In conclusion, in addition to blocking the transport of cyclic nucleotides, MRP4 inhibition may prevent thrombus formation in vitro and in vivo. Our findings also support the idea that MRP4 may represent a potential target for the development of novel therapeutic interventions for the treatment of thromboembolic disorders.
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Antioxidant activity in extracts of 27 indigenous Taiwanese vegetables.
Nutrients
PUBLISHED: 03-28-2014
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The objectives of this study were to identify the antioxidants and antioxidant axtivity in 27 of Taiwan's indigenous vegetables. Lycium chinense (Lc), Lactuca indica (Li), and Perilla ocymoides (Po) contained abundant quercetin (Que), while Artemisia lactiflora (Al) and Gynura bicolor (Gb) were rich in morin and kaempferol, respectively. Additionally, Nymphoides cristata (Nc) and Sechium edule (Se)-yellow had significantly higher levels of myricetin (Myr) than other tested samples. Cyanidin (Cyan) and malvidin (Mal) were abundant in Gb, Abelmoschus esculentus Moench (Abe), Po, Anisogonium esculentum (Retz.) Presl (Ane), Ipomoea batatas (Ib)-purple, and Hemerocallis fulva (Hf)-bright orange. Relatively high levels of Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenger were generated from extracts of Toona sinensis (Ts) and Po. Significant and positive correlations between antioxidant activity and polyphenols, anthocyanidins, Que, Myr, and morin were observed, indicating that these phytochemicals were some of the main components responsible for the antioxidant activity of tested plants. The much higher antioxidant activity of Po, Ts, and Ib (purple leaf) may be related to their higher Cyan, Que, and polyphenol content.
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Wild bitter gourd protects against alcoholic fatty liver in mice by attenuating oxidative stress and inflammatory responses.
Food Funct
PUBLISHED: 03-26-2014
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Bitter gourd (Momordica charantia L.) is a common vegetable grown widely in Asia that is used as a traditional medicine. The objective of this study was to investigate whether wild bitter gourd possessed protective effects against chronic alcohol-induced liver injury in mice. C57BL/6 mice were fed an alcohol-containing liquid diet for 4 weeks to induce alcoholic fatty liver. Meanwhile, mice were treated with ethanol extracts from four different wild bitter gourd cultivars: Hualien No. 1', Hualien No. 2', Hualien No. 3' and Hualien No. 4'. The results indicated that the daily administration of 500 mg kg body weight(-1) of a Hualien No. 3' extract (H3E) or a Hualien No. 4' extract (H4E) markedly reduced the steatotic alternation of liver histopathology. In addition, the activation of serum aminotransferases (AST and ALT) and the accumulation of hepatic TG content caused by alcohol were ameliorated. The hepatoprotective effects of H3E and H4E involved the enhancement of the antioxidant defence system (GSH, GPx, GRd, CAT and SOD), inhibition of lipid peroxidation (MDA) and reduction of pro-inflammatory cytokines (TNF-?, IL-1? and IL-6) in the liver. Moreover, H3E and H4E supplementation suppressed the alcohol-induced elevation of CYP2E1, SREBP-1, FAS and ACC protein expression. These results demonstrated that ethanol extracts of Hualien No. 3' and Hualien No. 4' have beneficial effects against alcoholic fatty liver, in which they attenuate oxidative stress and inflammatory responses.
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A 10-Gbps optical WiMAX transport system.
Opt Express
PUBLISHED: 03-26-2014
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A 10-Gbps optical worldwide interoperability for microwave access (WiMAX) transport system employing vertical cavity surface emitting laser (VCSEL) and spatial light modulator (SLM) with 16-quadrature amplitude modulation (QAM)-orthogonal frequency-division multiplexing (OFDM) modulating signal is proposed. With the assistance of equalizer and low noise amplifier (LNA) at the receiving site, good bit error rate (BER) performance, clear constellation map, and clear eye diagram are achieved in the proposed systems. An optical WiMAX transport system, transmitting 16-QAM-OFDM signal over a 6-m free-space link, with a data rate of 10 Gbps is successfully demonstrated. Such a 10-Gbps optical WiMAX transport system would be attractive for providing services including Internet and telecommunication services. Our proposed system is suitable for the free-space lightwave transport system in visible light communication (VLC) application.
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Role of a Janus kinase 2-dependent signaling pathway in platelet activation.
Thromb. Res.
PUBLISHED: 03-12-2014
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Janus kinases (JAKs) are intracellular non-receptor tyrosine kinases that transduce cytokine-mediated signals through a pathway mediated by JAK and the signal transducer and activator of transcription (STAT) proteins. The JAK-STAT pathway is involved in immune response, inflammation, and tumorigenesis. Platelets are anuclear blood cells that play a central role in hemostasis.
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Growth-differentiation factor-15 and major cardiac events.
Am. J. Med. Sci.
PUBLISHED: 02-14-2014
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Growth-differentiation factor (GDF)-15 is a strong predictor of cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). However, the effects of GDF-15 on left ventricular (LV) remodeling have not been clearly elucidated. The aim of this study is to investigate whether GDF-15 will be of benefit in predicting LV remodeling, heart failure and death in patients with STEMI.
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Leaf-derived cecidomyiid galls are sinks in Machilus thunbergii (Lauraceae) leaves.
Physiol Plant
PUBLISHED: 02-06-2014
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Three relevant hypotheses - nutrition, environment and the enemies hypothesis - often invoked to explore source and sink relationships between galls and their host plants are still under dispute. In this research, chlorophyll fluorescence, gas exchange capacity, stomatal conductance, total carbon and nitrogen, total soluble sugars and starches, and scanning and transmission electron microscopy of two types of galls were used to investigate source-sink relationships. Compared with host leaves, these galls demonstrated slightly lower chlorophyll fluorescence; however, gas exchange capacity and stomatal conductance were not detected at all. Scanning electron micrographs demonstrated that the abaxial epidermis of host leaves contain normal amounts of stomata, whereas no stomata were observed on the exterior and interior surfaces of both types of galls. In addition, gall inner surfaces were covered with many kinds of fungal hyphae. Gall total carbon (C) and nitrogen (N) levels were lower but the C/N ratio was higher in galls than host leaves. Both types of galls accumulated higher total soluble sugars and starches than host leaves. Transmission electron micrographs also revealed that both types of galls contain plastoglobuli and giant starch granules during gall development. Results strongly indicate that leaf-derived cecidomyiid galls are sinks in Machilus thunbergii leaves. However, it is perplexing how larvae cycle and balance CO2 and O2 in gall growth chambers without stomata.
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VIRIDANS STREPTOCOCCI IN PERITONEAL DIALYSIS PERITONITIS: CLINICAL COURSES AND LONG-TERM OUTCOMES.
Perit Dial Int
PUBLISHED: 02-06-2014
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The clinical courses and long-term outcomes of viridans streptococcus (VS) peritoneal dialysis (PD) peritonitis remain unclear.
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High-dialysate-glucose-induced oxidative stress and mitochondrial-mediated apoptosis in human peritoneal mesothelial cells.
Oxid Med Cell Longev
PUBLISHED: 01-29-2014
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Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5?mM, 84?mM, 138?mM, and 236?mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.
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Differentiation of lung stem/progenitor cells into alveolar pneumocytes and induction of angiogenesis within a 3D gelatin--microbubble scaffold.
Biomaterials
PUBLISHED: 01-29-2014
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The inability to adequately vascularize tissues in vitro or in vivo is a major challenge in lung tissue engineering. A method that integrates stem cell research with 3D-scaffold engineering may provide a solution. We have successfully isolated mouse pulmonary stem/progenitor cells (mPSCs) by a two-step procedure and fabricated mPSC-compatible gelatin/microbubble-scaffolds using a 2-channel fluid jacket microfluidic device. We then integrated the cells and the scaffold to construct alveoli-like structures. The mPSCs expressed pro-angiogenic factors (e.g., b-FGF and VEGF) and induced angiogenesis in vitro in an endothelial cell tube formation assay. In addition, the mPSCs were able to proliferate along the inside of the scaffolds and differentiate into type-II and type-I pneumocytes The mPSC-seeded microbubble-scaffolds showed the potential for blood vessel formation in both a chick chorioallantoic membrane (CAM) assay and in experiments for subcutaneous implantation in severe combined immunodeficient (SCID) mice. Our results demonstrate that lung stem/progenitor cells together with gelatin microbubble-scaffolds promote angiogenesis as well as the differentiation of alveolar pneumocytes, resulting in an alveoli-like structure. These findings may help advance lung tissue engineering.
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Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC ? 2-PKC and MAPK pathways.
Biomed Res Int
PUBLISHED: 01-25-2014
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Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60? ?M) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) ?2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC ?2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.
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Biosynthesis of streptolidine involved two unexpected intermediates produced by a dihydroxylase and a cyclase through unusual mechanisms.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-21-2014
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Streptothricin-F (STT-F), one of the early-discovered antibiotics, consists of three components, a ?-lysine homopolymer, an aminosugar D-gulosamine, and an unusual bicyclic streptolidine. The biosynthesis of streptolidine is a long-lasting but unresolved puzzle. Herein, a combination of genetic/biochemical/structural approaches was used to unravel this problem. The STT gene cluster was first sequenced from a Streptomyces variant BCRC 12163, wherein two gene products OrfP and OrfR were characterized in?vitro to be a dihydroxylase and a cyclase, respectively. Thirteen high-resolution crystal structures for both enzymes in different reaction intermediate states were snapshotted to help elucidate their catalytic mechanisms. OrfP catalyzes an Fe(II) -dependent double hydroxylation reaction converting L-Arg into (3R,4R)-(OH)2 -L-Arg via (3S)-OH-L-Arg, while OrfR catalyzes an unusual PLP-dependent elimination/addition reaction cyclizing (3R,4R)-(OH)2 -L-Arg to the six-membered (4R)-OH-capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT-F by a feeding experiment.
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Hinokitiol is a novel glycoprotein VI antagonist on human platelets.
Platelets
PUBLISHED: 01-16-2014
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Abstract Hinokitiol (4-isopropyl-tropolone) is a bioactive compound with various pharmacological activities that is found in the wood of cupressaceous plants. Platelet activation plays an important role in thrombogenesis. In our previous study, hinokitiol specifically inhibited collagen-induced platelet aggregation ex vivo and prolonged thrombogenesis in vivo. The glycoprotein (GP) VI and integrin ?2?1 are major collagen receptors that mediate platelet adhesion and aggregation. In our current study, we investigated which of these collagen receptors is involved in the hinokitiol-mediated inhibition of platelet activation. Treatment with 2-100?µM hinokitiol caused a dose-dependent right, parallel shift in the collagen concentration-response curve (0.5-10?µg/ml), with no change in the maximal responses. Furthermore, hinokitiol inhibited platelet aggregation and relative [Ca(2+)]i mobilization stimulated by convulxin, an agonist of GP VI, but not by aggretin, an agonist of integrin ?2?1, indicating that hinokitiol mediates the inhibition of platelet activation through GP VI, rather than through integrin ?2?1. Hinokitiol also specifically inhibited the convulxin-mediated activation of protein kinase C, phospholipase C?2, Akt, mitogen-activated protein kinases, and Lyn. Hinokitiol markedly diminished the co-immunoprecipitation of GP VI-bound Lyn after convulxin stimulation. In conclusion, hinokitiol, an antagonist of collagen GP VI may represent a novel antiplatelet drug for the prevention of thrombi associated with coronary and cerebral artery diseases.
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Chemical composition of seed oils in native Taiwanese Camellia species.
Food Chem
PUBLISHED: 01-13-2014
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The aim of this study was to examine the fatty acid (FA) composition and levels in seeds of twelve native Camellia species collected in different populations of major producing regions in Taiwan. The constituents of FAs varied within and among populations. Oleic acid (OA) was found to be the predominant FA constituent in all species. Remarkably high levels of unsaturated OA and linoleic acid (LA), found in two populations of Camellia tenuiflora (CT), C. transarisanensis (CTA), and C. furfuracea (CFA), were similar to those reported for olive oil. The levels of saturated palmitic acid (PA) from most of the tested seed oils were less than 13%. Among the different fats, some FAs can be used as functional ingredients for topical applications. The seed oils of CT, CTA, and CFA possess chemical compounds that make them useful in health-oriented cooking due to their high OA and LA contents and low PA content.
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Characteristics of endogenous ?-aminobutyric acid (GABA) in human platelets: functional studies of a novel collagen glycoprotein VI inhibitor.
J. Mol. Med.
PUBLISHED: 01-13-2014
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gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and it also appears in peripheral tissues. Platelets are anuclear blood cells that play a central role in hemostatic processes. Although platelets possess a GABA uptake system, the functional activity of GABA in platelets has remained unclear. We determined that GABA is abundantly distributed in the platelets at a concentration of approximately 1.03 ng/10(6) cells. GABA (0.5 ?M) specifically inhibited collagen-induced platelet activation accompanied by [Ca(2+)]i mobilization, phospholipase C?2, protein kinase C, Akt phosphorylation, and hydroxyl radical formation. In addition, GABA interfered with fluorescein isothiocyanate-collagen binding to platelet membranes and produced a concentration-dependent shift in the collagen concentration-response curve and a Schild plot slope of -0.96?±?0.11, indicating competitive inhibition. Platelet activation induced by convulxin, a glycoprotein VI agonist, was inhibited by GABA, whereas activation induced by the integrin ?(2)?(1) agonist, aggretin, was not. Immunoprecipitation and surface plasmon resonance revealed that GABA binds directly to glycoprotein VI in human platelets with equilibrium dissociation (binding) constant (K(D)) of 41.4 nM. The closure time of whole blood and the occlusion time of platelet plug formation were significantly prolonged by GABA in vivo. In this study, GABA is a specific inhibitor of collagen glycoprotein VI and may be involved in an endogenous negative feedback mechanism for platelet activation. Thus, GABA may represent a potential target for the development of novel interventions for the treatment of cardiovascular diseases associated with platelet activation, such as stroke and myocardial infarction.
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Intrathecal miR-183 delivery suppresses mechanical allodynia in mononeuropathic rats.
Eur. J. Neurosci.
PUBLISHED: 01-08-2014
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Members of the miR-183 family are unique in that they are highly abundant in sensory organs. In a recent study, significant downregulation was observed for miR-96 and miR-183 in the L5 dorsal root ganglion (DRG) 2 weeks after spinal nerve ligation (SNL). In this study, we focused on miR-183, which is the most regulated member of the miR-183 family, to look at the specific role on neuropathic pain. Persistent mechanical allodynia was induced with the L5 SNL model in 8-week-old male Sprague-Dawley rats. Paw withdrawal thresholds in response to mechanical stimuli were assessed with Von Frey filaments. Expression of miR-183 in the L5 DRG was assessed with quantitative real-time polymerase chain reaction (qPCR) analysis. Lentivirions expressing miR-183 were injected intrathecally into SNL rats. Changes in mechanical allodynia were assessed with Von Frey filaments. In addition, changes in the predicted target genes of miR-183 were assessed with qPCR. L5 SNL produced marked mechanical allodynia in the ipsilateral hindpaws of adult rats, beginning at postoperative day 1 and continuing to day 14. L5 SNL caused significant downregulation of miR-183 in adult DRG cells. Intrathecal administration of lentivirions expressing miR-183 downregulated SNL-induced increases in the expression of Nav1.3 and brain-derived neurotrophic factor (BDNF), which correlated with the significant attenuation of SNL-induced mechanical allodynia. Our results show that SNL-induced mechanical allodynia is significantly correlated with the decreased expression of miR-183 in DRG cells. Replacement of miR-183 downregulates SNL-induced increases in Nav1.3 and BDNF expression, and attenuates SNL-induced mechanical allodynia.
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Structure and mechanism of a nonhaem-iron SAM-dependent C-methyltransferase and its engineering to a hydratase and an O-methyltransferase.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 01-06-2014
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In biological systems, methylation is most commonly performed by methyltransferases (MTs) using the electrophilic methyl source S-adenosyl-L-methionine (SAM) via the S(N)2 mechanism. (2S,3S)-?-Methylphenylalanine, a nonproteinogenic amino acid, is a building unit of the glycopeptide antibiotic mannopeptimycin. The gene product of mppJ from the mannopeptimycin-biosynthetic gene cluster is the MT that methylates the benzylic C atom of phenylpyruvate (Ppy) to give ?MePpy. Although the benzylic C atom of Ppy is acidic, how its nucleophilicity is further enhanced to become an acceptor for C-methylation has not conclusively been determined. Here, a structural approach is used to address the mechanism of MppJ and to engineer it for new functions. The purified MppJ displays a turquoise colour, implying the presence of a metal ion. The crystal structures reveal MppJ to be the first ferric ion SAM-dependent MT. An additional four structures of binary and ternary complexes illustrate the molecular mechanism for the metal ion-dependent methyltransfer reaction. Overall, MppJ has a nonhaem iron centre that bind, orients and activates the ?-ketoacid substrate and has developed a sandwiched bi-water device to avoid the formation of the unwanted reactive oxo-iron(IV) species during the C-methylation reaction. This discovery further prompted the conversion of the MT into a structurally/functionally unrelated new enzyme. Through stepwise mutagenesis and manipulation of coordination chemistry, MppJ was engineered to perform both Lewis acid-assisted hydration and/or O-methyltransfer reactions to give stereospecific new compounds. This process was validated by six crystal structures. The results reported in this study will facilitate the development and design of new biocatalysts for difficult-to-synthesize biochemicals.
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Acinetobacter Peritoneal Dialysis Peritonitis: A Changing Landscape over Time.
PLoS ONE
PUBLISHED: 01-01-2014
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Acinetobacter species are assuming an increasingly important role in modern medicine, with their persistent presence in health-care settings and antibiotic resistance. However, clinical reports addressing this issue in patients with peritoneal dialysis (PD) peritonitis are rare.
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The role of Si interstitials in the migration and growth of Ge nanocrystallites under thermal annealing in an oxidizing ambient.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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We report a unique growth and migration behavior of Ge nanocrystallites mediated by the presence of Si interstitials under thermal annealing at 900°C within an H2O ambient. The Ge nanocrystallites were previously generated by the selective oxidation of SiGe nanopillars and appeared to be very sensitive to the presence of Si interstitials that come either from adjacent Si3N4 layers or from within the oxidized nanopillars. A cooperative mechanism is proposed, wherein the Si interstitials aid in both the migration and coarsening of these Ge nanocrystallites through Ostwald ripening, while the Ge nanocrystallites, in turn, appear to enhance the generation of Si interstitials through catalytic decomposition of the Si-bearing layers.
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Correlation of interleukin-17-producing effector memory T cells and CD4+CD25+Foxp3 regulatory T cells with the phosphate levels in chronic hemodialysis patients.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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Hyperparathyroidism and hyperphosphatemia contribute to the inflammatory effects in chronic hemodialysis (HD) patients. Interleukin-17-producing CD4+ effector memory T (Th17) cells and CD4+CD25+Foxp3 regulatory T (Treg) cells both play critical roles in immune activation and inflammation. We investigated the relationship between the Treg and Th17 cells and the phosphate level in chronic HD patients.
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Target-controlled infusion vs. manually controlled infusion of propofol with alfentanil for bidirectional endoscopy: a randomized controlled trial.
Endoscopy
PUBLISHED: 10-28-2013
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The best anesthesia methods for analgesia and sedation during gastrointestinal endoscopy are still debated. The aim of this study was to compare the recovery time, clinical presentations, and satisfaction between target-controlled infusion (TCI) and manually controlled infusion (MCI) in same-day bidirectional endoscopy (esophagogastroduodenoscopy followed by colonoscopy).
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Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis.
BMJ
PUBLISHED: 10-26-2013
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To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes.
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Risk of Stroke in Long-term Dialysis Patients Compared With the General Population.
Am. J. Kidney Dis.
PUBLISHED: 10-16-2013
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Patients undergoing maintenance dialysis are at increased risk of stroke.
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Investigating the effects of streamline-based fiber tractography on matrix scaling in brain connective network.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Investigating the brain connective network using the modern graph theory has been widely applied in cognitive and clinical neuroscience research. In this study, we aimed to investigate the effects of streamline-based fiber tractography on the change of network properties and established a systematic framework to understand how an adequate network matrix scaling can be determined. The network properties, including degree, efficiency and betweenness centrality, show similar tendency in both left and right hemispheres. By employing the curve-fitting process with exponential law and measuring the residuals, the association between changes of network properties and threshold of track numbers is found and an adequate range of investigating the lateralization of brain network is suggested. The proposed approach can be further applied in clinical applications to improve the diagnostic sensitivity using network analysis with graph theory.
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Estimation of fiber orientation by filtered q-ball imaging*.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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We proposed a filtered q-ball imaging (fQBI) method for the reconstruction of fiber orientation distribution function (ODF) together with the quantitative comparison to unfiltered QBI. The filter kernel increases the high angular frequency content that is beneficial for the angular resolution in resolving crossing fibers. Through a series of simulations using Monte-Carlo model, the angular resolution of fQBI was demonstrated better than traditional QBI but the deviation of fiber orientation estimate also becomes larger. The improvement of the angular resolution can also reduce the underestimation of separation angles as well as the bias of fiber orientation estimations. In conclusion, fQBI was demonstrated to improve the angular resolution of QBI in resolving crossing fibers. This improvement will be helpful to precisely reconstruct fiber tract and brain network in applications by QBI.
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Full-duplex lightwave transport systems based on long-haul SMF and optical free-space transmissions.
Opt Express
PUBLISHED: 10-10-2013
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A full-duplex lightwave transport system employing wavelength-division-multiplexing (WDM) and optical add-drop multiplexing techniques, as well as optical free-space transmission scheme is proposed and experimentally demonstrated. Over an 80-km single-mode fiber (SMF) and 2.4 m optical free-space transmissions, impressive bit error rate (BER) performance is obtained for long-haul fiber link and finite free-space transmission distance. Such a full-duplex lightwave transport system based on long-haul SMF and optical free-space transmissions has been successfully demonstrated, which cannot only present its advancement in lightwave application, but also reveal its simplicity and convenience for the real implementation. Our proposed systems are suitable for the lightwave communication systems in wired and wireless transmissions.
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Chlorophyll-related compounds inhibit cell adhesion and inflammation in human aortic cells.
J Med Food
PUBLISHED: 09-25-2013
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The objectives of this study were to investigate the effects of chlorophyll-related compounds (CRCs) and chlorophyll (Chl) a+b on inflammation in human aortic endothelial cells. Adhesion molecule expression and interleukin (IL)-8, nuclear factor (NF)-?B p65 protein, and NF-?B and activator protein (AP)-1 DNA binding were assessed. The effects of CRCs on inflammatory signaling pathways of signal transducers and activators of transcription 3 (STAT3) and mothers against decapentaplegic homolog 4, respectively induced by IL-6 and transforming growth factor (TGF)-?, in human aortic smooth muscle cells cultured in vitro were also investigated. HAECs were pretreated with 10 ?M of CRCs, Chl a+b, and aspirin (Asp) for 18 h followed by tumor necrosis factor (TNF)-? (2 ng/mL) for 6 h, and U937 cell adhesion was determined. TNF-?-induced monocyte-endothelial cell adhesion was significantly inhibited by CRCs. Moreover, CRCs and Chl a+b significantly attenuated vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and IL-8 expressions. Treatments also significantly decreased in NF-?B expression, DNA binding, and AP-1 DNA binding by CRCs and Asp. Thus, CRCs exert anti-inflammatory effects through modulation of NF-?B and AP-1 signaling. Ten micromoles of CRCs and Asp upregulated the expression of mothers against decapentaplegic homolog 4 (Drosophila) (SMAD4) in the TGF-? receptor signaling pathway, and SMAD3/4 transcription activity was also increased. Ten micromoles of CRCs were able to potently inhibit STAT3-binding activity by repressing IL-6-induced STAT3 expression. Our results provide a potential mechanism that explains the anti-inflammatory activities of these CRCs.
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Pulsed Radiofrequency Reduced Complete Freunds Adjuvant-induced Mechanical Hyperalgesia via the Spinal c-Jun N-terminal Kinase Pathway.
Cell. Mol. Neurobiol.
PUBLISHED: 09-12-2013
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Pulsed radiofrequency (PRF) treatment involves the pulsed application of a radiofrequency electric field to a nerve. The technology offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freunds adjuvant (CFA) induced inflammatory pain. The profile of spinal c-Jun N-terminal kinases (JNKs) phosphorylation was evaluated to elucidate the potential mechanism. Injection of CFA into the unilateral hind paw of rats induced mechanical hyperalgesia in both the ipsilateral and contralateral hind paws. We administered 500-kHz PRF treatment in 20-ms pulses, at a rate of 2 Hz (2 pulses per second) either to the sciatic nerve in the mid-thigh, or to the L4 anterior primary ramus just distal to the intervertebral foramen in both the CFA group and no-PRF group rats. Tissue samples were examined at 1, 3, 7, and 14 days following PRF treatments. Behavioral studies showed that PRF applied close to the dorsal root ganglion (DRG) significantly attenuated CFA-induced mechanical hyperalgesia compared to no-PRF group (P < .05). And western blotting revealed significant attenuation of the activation of JNK in the spinal dorsal horn compared to no-PRF group animals (P < .05). Application of PRF close to DRG provides an effective treatment for CFA-induced persistent mechanical hyperalgesia by attenuating JNK activation in the spinal dorsal horn.
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Antioxidant activity of herbaceous plant extracts protect against hydrogen peroxide-induced DNA damage in human lymphocytes.
BMC Res Notes
PUBLISHED: 08-19-2013
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Herbaceous plants containing antioxidants can protect against DNA damage. The purpose of this study was to evaluate the antioxidant substances, antioxidant activity, and protection of DNA from oxidative damage in human lymphocytes induced by hydrogen peroxide (H2O2). Our methods used acidic methanol and water extractions from six herbaceous plants, including Bidens alba (BA), Lycium chinense (LC), Mentha arvensis (MA), Plantago asiatica (PA), Houttuynia cordata (HC), and Centella asiatica (CA).
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Autophagy induction promotes aristolochic acid-I-induced renal injury in vivo and in vitro.
Toxicology
PUBLISHED: 06-18-2013
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Studies have found that ingestion of aristolochic acid (AA) causes nephropathy first by inducing renal tubular cell apoptosis acutely. It is currently unknown whether crosstalk between autophagy and apoptosis orchestrates the fate of tubular cells in acute AA nephropathy. We tested this hypothesis by acute administration of AA in vivo and in vitro. Autophagy was first induced in vivo through enhancing Atg5 and LC3-II expressions in kidneys of AA-I-treated rats. Punctuate LC3-GFP dots and autophagosomes were detected in this acute AA-I nephropathy rat model. We subsequently utilized normal rat renal proximal tubular epithelial cells (NRK52E) to study the autophagy mechanisms involved in acute AA-I nephropathy, with 100?M AA-I (median lethal dose 50) given in vitro. Cleavage of poly (ADP-ribose) polymerase (PARP), nuclear condensation, and fragmentation were demonstrated in the AA-I-treated NRK52E cells. Furthermore, AA-I induced Atg5 and LC3-II expressions and punctuated LC3-GFP dots. Autophagy flux by using lysosome inhibitor E64 induced the accumulation of LC3-II, which further promoted apoptosis through enhancing PARP cleavage. Inhibition of autophagy by 3-methyl adenine also led to the attenuation of AA-I-induced apoptosis, manifesting as decreased PARP cleavage, nuclei condensation, and decreased the number of cells negative for acridine orange/ethidium bromide staining. In addition, knockdown of Atg5 by short hairpin RNA attenuated LC3-II expression and PARP cleavage in NRK52E cells. Taken together, these findings suggested that the acute phase of AA-I-induced nephropathy is associated with induction of Atg5-dependent autophagy, which promotes renal tubular cell apoptosis.
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A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis.
Pharm Biol
PUBLISHED: 06-12-2013
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Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs.
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Altered Mitochondrial ATP Synthase Expression in the Rat Dorsal Root Ganglion After Sciatic Nerve Injury and Analgesic Effects of Intrathecal ATP.
Cell. Mol. Neurobiol.
PUBLISHED: 05-24-2013
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Mitochondrial ATP synthase has multiple interdependent biological functions in neurons. Among them, ATP generation and regulation are the most important. The present study investigated whether the expression of mitochondrial ATP synthase correlates with symptoms of neuropathic pain in adult rats after axotomy, and whether intrathecal ATP administration is therapeutic in these neuropathic rats. Male Sprague-Dawley rats received left sciatic nerve transection (axotomy) and were randomly designated to a control (sham-operated) group, a neuropathic pain group (axotomy), a neuropathic pain and intrathecal sterile saline group, and a neuropathic pain and intrathecal ATP group. The thermal and mechanical sensitivity tests were performed at 1, 3, 5, and 7 days after axotomy. Left L4-L5 dorsal root ganglions (DRGs) were harvested to assess mitochondrial ATP synthase by immunoblotting and immunohistochemistry. After nerve injury, the expression of mitochondrial ATP synthase was decreased in protein extracts and was found mainly in C-fiber and A-? fiber neurons of the DRGs. The decreased expression of mitochondrial ATP synthase and its subcellular localization were related to thermal and mechanical hyperalgesia. Administration of intrathecal ATP significantly attenuated thermal and mechanical hypersensitivity throughout the experimental period, which suggests its potential role in the treatment of neuropathic pain.
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Cellulose-Based Diagnostic Devices for Diagnosing Serotype-2 Dengue Fever in Human Serum.
Adv Healthc Mater
PUBLISHED: 04-24-2013
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Here, two types of cellulose-based in vitro diagnostic devices are demonstrated for the diagnosis of dengue virus infection in both buffer system and human serum: 1) paper-based ELISA for providing the semiquantitative information of the disease activity of serotype-2 dengue fever to healthcare persons (i.e., monitoring the disease activity with a specific serotype in single patients); 2) lateral flow immunoassays to screen for infection with serotype-2 dengue fever (i.e., rapid YES or NO diagnosis prepared for large populations, in terms of global public health). Paper-based ELISA (specific to serotype-2 dengue fever), which builds off of our previous studies and a revised previous ELISA procedure, owns multiple advantages: 1) high sensitivity (about 40 times higher than the current ELISA-based approaches, due to our therapeutic-based monoclonal antibody) and specificity (specific to dengue virus serotype-2 nonstructural protein-1 antigens); 2) tiny amount of sample and reagent used for single tests; 3) short operating duration (i.e., rapid diagnostic device); and, 4) inexpensiveness (appropriate for use in all developing and underdeveloped nations of the world). Due to the higher sensitivity and shorter operating duration of paper-based ELISA (compared with conventional ELISA, and lateral flow immunoassays also performed in this study), this study has not only been able to perform the diagnosis of dengue virus serotype-2 nonstructural protein-1 antigens in both buffer system and human serum but also to evaluate dengue virus serotype-2 envelope proteins in the buffer system, thus successfully achieving the first such use of these proteins as the target antigen for the development of diagnostic tools. These results provide a more comprehensive understanding for the genesis of dengue fever diagnostic tools (through antibody-antigen recognition).
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Metabolic syndrome and abdominal fat are associated with inflammation, but not with clinical outcomes, in peritoneal dialysis patients.
Cardiovasc Diabetol
PUBLISHED: 04-13-2013
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BACKGROUND: In the general population, metabolic syndrome (MetS) is correlated with visceral fat and a risk factor for cardiovascular disease (CVD); however, little is known about the significance of abdominal fat and its association with inflammation and medication use in peritoneal dialysis (PD) patients. We investigated the relationship of visceral fat area (VFA) with C-reactive protein (CRP) levels and medication use in PD patients and followed their clinical outcomes. METHODS: In a prospective study from February 2009 to February 2012, we assessed diabetes mellitus (DM) status, clinical and PD-associated characteristics, medication use, CRP levels, components of MetS, and VFA in 183 PD patients. These patients were categorized into 3 groups based on MetS and DM status: non-MetS (group 1, n = 73), MetS (group 2, n = 65), and DM (group 3, n = 45). VFA was evaluated by computed tomography (CT) and corrected for body mass index (BMI). RESULTS: Patients in group 1 had smaller VFAs than patients in groups 2 and 3 (3.2 +/- 1.8, 4.6 +/- 1.9, and 4.9 +/- 2.0 cm2/[kg/m2], respectively, P < 0.05) and lower CRP levels (0.97 +/- 2.31, 1.27 +/- 2.57, and 1.11 +/- 1.35 mg/dL, respectively, P < 0.05). VFA increased with the number of criteria met for MetS. After adjusting for age, body weight, and sex, CRP and albumin levels functioned as independent positive predictors of VFA; on other hand, the use of renin-angiotensin system blockers was inversely correlated with VFA in PD patients without DM. In the survival analysis, DM patients (group 3) had the poorest survival among the 3 groups, but no significant differences were found between groups 1 and 2. CONCLUSION: This study showed that VFA and MetS are associated with CRP levels but cannot predict survival in PD patients without DM. The complex relationship of nutritional parameters to VFA and MetS may explain these results. The type of antihypertensive medication used was also associated with the VFA. The mechanisms behind these findings warrant further investigation.
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Pulsed radiofrequency treatment attenuates increases in spinal excitatory amino acid release in rats with adjuvant-induced mechanical allodynia.
Neuroreport
PUBLISHED: 04-11-2013
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Excitatory amino acids (EAAs) play a critical role in the development of peripheral tactile and thermal hypersensitivity after the induction of paw inflammation in rats. We used a spinal microdialysis model to examine the effect of complete Freunds adjuvant (CFA)-induced inflammation on the spinal release of EAAs and assessed the antinociceptive effect of pulsed radiofrequency (PRF). CFA was injected into the plantar surface of the left hind paw to induce inflammation. Either the sciatic nerve of adult CFA rats in the mid-thigh, or the L4 anterior primary ramus just distal to the intervertebral foramen was treated with PRF (20 ms, 500 kHz pulses) at a rate of 2 Hz and a maximum temperature of 42°C. Concentrations of amino acids in the dialysate from the spinal microdialysis catheter and mechanical paw withdrawal threshold were determined to evaluate the analgesic effect of PRF. An intraplantar injection of CFA induced a significant release of glutamate, aspartate, and citrulline for 7 days. The behavior tests showed that PRF administered to the anterior ramus, just distal to the intervertebral foramen, significantly reduced mechanical allodynia, and microanalysis showed a significant suppression of EAAs and citrulline release. The antiallodynic effect of PRF was observed the day following CFA injection and maintained for 7 days. We showed that PRF administered adjacent to the dorsal root ganglion suppresses the release of EAAs, which may account for the PRF antiallodynic properties observed in adjuvant-induced inflammation.
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Microalbuminuria screening for detecting chronic kidney disease in the general population: a systematic review.
Ren Fail
PUBLISHED: 03-28-2013
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Microalbuminuria screening is widely used in high-risk populations but seldom used in the general population for detecting chronic kidney disease (CKD). Systematic reviews focused on screening for CKD are rare, and the issues about microalbuminuria screening in the general population have never been reviewed. We systematically reviewed studies regarding microalbuminuria screening and evaluated the benefits and harms of this screening method in the general population.
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Blocking TNF-? enhances Pseudomonas aeruginosa-induced mortality in burn mice through induction of IL-1?.
Cytokine
PUBLISHED: 03-24-2013
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Tumor necrosis factor (TNF?) is a proinflammatory cytokine and has been a target for intervention in human sepsis. However, inhibition of TNF-? with a high dose of a TNF-receptor fusion protein in patients with septic shock worsened patient survival. This study was designed to investigate whether blocking TNF-? enhances mortality in infected burn mice through the induction of IL-1?.
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Epigenetic histone methylation regulates transforming growth factor ?-1 expression following bile duct ligation in rats.
J. Gastroenterol.
PUBLISHED: 03-18-2013
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Multiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor ?-1 (TGF-?1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-?1 gene expression in rat liver.
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Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series.
BMC Nephrol
PUBLISHED: 02-21-2013
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BACKGROUND: Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. METHODS: We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. RESULTS: Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). CONCLUSION: Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate.
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Lean body mass predicts long-term survival in Chinese patients on peritoneal dialysis.
PLoS ONE
PUBLISHED: 01-25-2013
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Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients outcomes and the factors related to increasing LBM are seldom reported.
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Glycosylated hemoglobin and albumin-corrected fructosamine are good indicators for glycemic control in peritoneal dialysis patients.
PLoS ONE
PUBLISHED: 01-24-2013
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Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients.
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Brazilin isolated from Caesalpinia sappan L. acts as a novel collagen receptor agonist in human platelets.
J. Biomed. Sci.
PUBLISHED: 01-22-2013
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Brazilin, isolated from the heartwood of Caesalpinia sappan L., has been shown to possess multiple pharmacological properties.
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P-cresol induces disruption of cardiomyocyte adherens junctions.
Toxicology
PUBLISHED: 01-15-2013
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Higher serum levels of p-cresol in chronic kidney disease populations have been associated with increased cardiovascular mortality. However, studies on how p-cresol affects intercellular junctions between cardiomyocytes were limited. This study investigated the effect of p-cresol on adherens junction (AJ) of neonatal cultured cardiomyocytes and its underlying mechanism. A loss of N-cadherin and p120-catenin (p120ctn) immunostaining from cell-cell contact sites was noted by p-cresol treatment. In addition, p-cresol disrupted AJs by inducing formation of intercellular gaps. Our previous study has revealed that p-cresol increased intracellular calcium levels and activated protein kinase C? (PKC?) by phosphorylation. The PKC? activation was involved in the p-cresol-mediated AJ disassembly, since pharmacological inhibition of PKC? abolished the above-mentioned p-cresol effect. This PKC? activation also led to the serine dephosphorylation of p120ctn and caused the dissociation of p120ctn from N-cadherin. This hypothesis was further confirmed in H9c2 cells by siRNA approach. SiRNA knockdown of PKC? prevented p-cresol-induced serine dephosphorylation of p120ctn and splitting of AJ. In conclusion, p-cresol caused PKC?-dependent AJ disassembly of cardiomyocytes, which might be related to asychronized contraction.
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Novel bioactivity of ellagic Acid in inhibiting human platelet activation.
Evid Based Complement Alternat Med
PUBLISHED: 01-04-2013
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Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80? ? M) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80? ? M) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca(2+)] i mobilization, and the phosphorylation of phospholipase C (PLC) ? 2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt, as well as hydroxyl radical (OH(?)) formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLC?2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.
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Mechanisms of andrographolide-induced platelet apoptosis in human platelets: regulatory roles of the extrinsic apoptotic pathway.
Phytother Res
PUBLISHED: 01-04-2013
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Andrographolide, a novel nuclear factor-?B (NF-?B) inhibitor, is isolated from the leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by inhibition of the p38 MAPK/(?) HO-NF-?B-ERK2 cascade. Although platelets are anucleated cells, apoptotic machinery apparatus recently has been found to regulate platelet activation and limit platelet lifespan. Therefore, we further investigated the regulatory effects of andrographolide on platelet apoptotic events. In this study, apoptotic signaling events for caspase-3, -8, and Bid were time (10-60?min)- and dose (25-100???)-dependently activated by andrographolide in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. In addition, caspase-8 inhibitor (z-IETD-fmk, 50???) was found to reverse andrographolide-induced caspase-8 activation, whereas the antagonistic anti-Fas receptor (ZB4, 500?ng/mL) and anti-tumor necrosis factor-R1 (H398, 10?µg/mL) monoclonal antibodies did not. In conclusion, this study for the first time demonstrated that andrographolide might limit platelet lifespan by initiating the caspase-8-dependent extrinsic apoptotic pathway, in spite of no direct evidence that death receptors are involved in this process proved. Overall, the various medicinal properties of andrographolide suggest its potential value in treating patients with thromboembolic disorders.
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Comparison of Immediate and 2-Year Outcomes between Excimer Laser-Assisted Angioplasty with Spot Stent and Primary Stenting in Intermediate to Long Femoropopliteal Disease.
ScientificWorldJournal
PUBLISHED: 01-01-2013
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Background. To compare the clinical outcomes between excimer laser-assisted angioplasty (ELA) with spot stent (group A) and primary stenting (group B) in intermediate to long femoropopliteal disease. Methods. Outcomes of 105 patients totaling 119 legs treated with two different strategies were analyzed retrospectively in a prospectively maintained database. Results. Baseline characteristics were similar in both groups. Better angiographic results and lesser increase of serum C-reactive protein levels (0.60 ± 0.72 versus 2.98 ± 0.97?mg/dL, P < 0.001) after the intervention were obtained in Group B. Group A had inferior 1-year outcomes due to higher rate of binary restenosis (67% versus 32%, P = 0.001) and lower rate of primary patency (40% versus 58%, P = 0.039). Rates of amputation-free survival, target vessel revascularization, assisted primary patency, and stent fracture at 24 months were similar in both groups (80% versus 82%, P = 0.979, 65% versus 45%, P = 0.11, 78% versus 80%, P = 0.75 and 6.3% versus 6.8%, P = 0.71, resp.). Conclusion. Greater vascular inflammation after ELA with spot stent resulted in earlier restenosis and inferior 1-year clinical outcomes than primary stenting. This benefit was lost in the primary stenting group at 2 years due to late catch-up restenosis. Active surveillance with prompt intervention was required to maintain the vessel patency.
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High peritoneal KT/V and peritonitis rates are associated with peritoneal calcification.
PLoS ONE
PUBLISHED: 01-01-2013
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Peritoneal calcification (PC) is a specific finding in patients undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and impacts in PD patients remain unclear. The present study investigated these issues and provided information useful for the management of PC.
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Citrobacter peritoneal dialysis peritonitis: rare occurrence with poor outcomes.
Int J Med Sci
PUBLISHED: 01-01-2013
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Non-Pseudomonas gram-negative bacteria are responsible for an increasing proportion of cases of peritoneal dialysis (PD)-related peritonitis. The role of Citrobacter species in the etiology of PD-related peritonitis is often underestimated. In the present study, we aimed to describe the clinical features, laboratory findings, and short- and long-term outcomes in PD-related peritonitis caused by Citrobacter.
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Abdominal obesity is associated with peripheral artery disease in hemodialysis patients.
PLoS ONE
PUBLISHED: 01-01-2013
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Peripheral arterial disease (PAD) is a leading cause of morbidity in hemodialysis (HD) patients. Recent evidence suggests that abdominal obesity (AO) may play a role in PAD. However, the association between AO and PAD has not been thoroughly studied in HD patients.
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Altered molecular repertoire of immune system by renal dysfunction in the elderly: is prediction and targeted prevention in the horizon?
EPMA J
PUBLISHED: 01-01-2013
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Patients on chronic hemodialysis (HD) have impaired cellular and humoural immunity. The percentage of elderly people among the total population in Taiwan is increasing dramatically, and HD is the primary alternative for renal replacement therapy when renal function declines. Activated vitamin D is widely used in HD patients with secondary hyperparathyroidism (SHPT) and is a well-known immunomodulatory agent. Personalized medicine and integrative medical approach has been a trend in current clinical practice. Can we improve their immune function using vitamin D in spite of the mineral aspect? Here, we investigated the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and T cell differentiation in chronic HD patients.
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Dissecting the mechanisms of left ventricular diastolic dysfunction and inflammation in peritoneal dialysis patients.
PLoS ONE
PUBLISHED: 01-01-2013
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Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group.
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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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