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Find video protocols related to scientific articles indexed in Pubmed.
Safety and efficacy of retrograde intrarenal surgery for renal stones in patients with a solitary kidney: a single-center experience.
J. Endourol.
PUBLISHED: 08-06-2014
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Abstract Background and Purpose: The management of urolithiasis in patients with a solitary kidney is challenging for endourologists. This study was aimed at evaluating the safety and efficacy of retrograde intrarenal surgery (RIRS) in the treatment of such patients with renal stones.
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The development of Wilms tumor: from WT1 and microRNA to animal models.
Biochim. Biophys. Acta
PUBLISHED: 05-26-2014
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Wilms tumor recapitulates the development of the kidney and represents a unique opportunity to understand the relationship between normal and tumor development. This has been illustrated by the findings that mutations of Wnt/?-catenin pathway-related WT1, ?-catenin, and WTX together account for about one-third of Wilms tumor cases. While intense efforts are being made to explore the genetic basis of the other two-thirds of tumor cases, it is worth noting that, epigenetic changes, particularly the loss of imprinting of the DNA region encoding the major fetal growth factor IGF2, which results in its biallelic over-expression, are closely associated with the development of many Wilms tumors. Recent investigations also revealed that mutations of Drosha and Dicer, the RNases required for miRNA generation, and Dis3L2, the 3'-5' exonuclease that normally degrades miRNAs and mRNAs, could cause predisposition to Wilms tumors, demonstrating that miRNA can play a pivotal role in Wilms tumor development. Interestingly, Lin28, a direct target of miRNA let-7 and potent regulator of stem cell self-renewal and differentiation, is significantly elevated in some Wilms tumors, and enforced expression of Lin28 during kidney development could induce Wilms tumor. With the success in establishing mice nephroblastoma models through over-expressing IGF2 and deleting WT1, and advances in understanding the ENU-induced rat model, we are now able to explore the molecular and cellular mechanisms induced by these genetic, epigenetic, and miRNA alterations in animal models to understand the development of Wilms tumor. These animal models may also serve as valuable systems to assess new treatment targets and strategies for Wilms tumor.
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[Determination of estrogen residues in drinking water by on-line solid phase extraction based on sol-gel technique coupled with high performance liquid chromatography].
Se Pu
PUBLISHED: 05-15-2014
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A method for the determination of diethylstilbestrol (DES), hexestrol (HEX) and dienestrol (DS) residues in drinking water was established by on-line solid phase extraction (SPE) coupled with high performance liquid chromatography (HPLC). The material synthesized on the base of sol-gel technology was employed as adsorbent. This material was prepared using 3-aminopropyltriethoxysilane (APTES) as the functional monomer, tetraethoxysilane (TEOS) as the crosslinking agent, and acetic acid as the initiator. The synthesized adsorbent showed outstanding property for the estrogen extraction. The estrogen can be caught effectively from water samples and the extraction can be achieved rapidly. Some important parameters, such as pH of sample solution, eluent solvents, loading flow rate, which might influence extraction efficiency, were optimized. The results indicated that the limit of detection (S/N = 3) of the developed method could reach 0.07-0.13 microg/L under the conditions of pH 7.0 of sample solution, methanol and 1% (v/v) acetic acid aqueous solution as the eluent solvent and the loading flow rate of 2 mL/min. The recoveries of the three estrogens from the water samples at three spiked levels ranged from 82.31% to 99.43% with RSD of 1.61%-7.15%. The method was simple, rapid, and suitable to detect the trace residues of estrogens in drinking water.
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Bromate removal from aqueous solutions by ordered mesoporous carbon.
Environ Technol
PUBLISHED: 03-21-2014
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We investigated the feasibility of using ordered mesoporous carbon (OMC) for bromate removal from water. Batch experiments were performed to study the influence of various experimental parameters such as the effect of contact time, adsorbent dosage, initial bromate concentration, temperature, pH and effect of competing anions on bromate removal by OMC. The adsorption kinetics indicates that the uptake rate ofbromate was rapid at the beginning: 85% adsorption was completed in 1 h and equilibrium was achieved within 3 h. The sorption process was well described with pseudo-second-order kinetics. The maximum adsorption capacity of OMC for bromate removal was 17.6 mg g(-1) at 298 K. The adsorption data fit the Freundlich model well. The amount of bromate removed was found to be proportional to the influent bromate concentration. The effects of competing anions and solution pH (3-11) were negligible. These limited data suggest that OMC can be effectively utilized for bromate removal from drinking water.
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Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects.
Cell Rep
PUBLISHED: 03-09-2014
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Mammalian cells generate citrate by decarboxylating pyruvate in the mitochondria to supply the tricarboxylic acid (TCA) cycle. In contrast, hypoxia and other impairments of mitochondrial function induce an alternative pathway that produces citrate by reductively carboxylating ?-ketoglutarate (AKG) via NADPH-dependent isocitrate dehydrogenase (IDH). It is unknown how cells generate reducing equivalents necessary to supply reductive carboxylation in the setting of mitochondrial impairment. Here, we identified shared metabolic features in cells using reductive carboxylation. Paradoxically, reductive carboxylation was accompanied by concomitant AKG oxidation in the TCA cycle. Inhibiting AKG oxidation decreased reducing equivalent availability and suppressed reductive carboxylation. Interrupting transfer of reducing equivalents from NADH to NADPH by nicotinamide nucleotide transhydrogenase increased NADH abundance and decreased NADPH abundance while suppressing reductive carboxylation. The data demonstrate that reductive carboxylation requires bidirectional AKG metabolism along oxidative and reductive pathways, with the oxidative pathway producing reducing equivalents used to operate IDH in reverse.
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Efficacy of intravenous propacetamol hydrochloride in the treatment of an acute attack of migraine.
Eur. J. Intern. Med.
PUBLISHED: 02-20-2014
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Triptans are a family of selective serotonin (5-HT1B/1D) receptor agonists that are widely used to treat acute migraine attacks. Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine.
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White matter lesions in chronic migraine with medication overuse headache: a cross-sectional MRI study.
J. Neurol.
PUBLISHED: 01-27-2014
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Analgesic overuse often happens to migraine patients, especially chronic migraineurs, and migraine has been demonstrated to be associated with white matter lesions (WMLs). The aim of this study was to investigate the relationship between medication overuse headache (MOH) and WMLs in chronic migraine (CM) patients. Subjects were enrolled and divided into three groups: healthy controls, CM without MOH (CMwoMOH), and CM with MOH (CM-MOH). Most of the CM patients used non-steroidal anti-inflammatory drugs (NSAIDs) as acute headache medications. All the participants underwent magnetic resonance imaging scans and images were obtained for WML evaluation with semiquantitative scales. One hundred and forty-one participants were included, 45 of them for controls, 38 for CMwoMOH, and 58 for CM-MOH. In women, CMwoMOH patients had a higher prevalence of high WML load compared with controls and CM-MOH patients. In men, however, all the study groups showed no differences in the prevalence of high WML load. CMwoMOH women had increased risks of high deep white matter lesion (DWML) load compared with controls, while they had no risks of high periventricular white matter lesion (PVWML) load. CM-MOH women had no risks of high DWML load, but they had reduced risks of high PVWML load. The association of CM-MOH with high WML load in women was not changed when compared with CMwoMOH. Age was independently associated with high WML load among women. These data suggest that MOH caused by NSAIDs is not a risk factor for WMLs. Rather, NSAID overuse probably protects MOH patients from WMLs through anti-inflammatory effects.
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Strategies to mitigate peanut allergy: production, processing, utilization, and immunotherapy considerations.
Annu Rev Food Sci Technol
PUBLISHED: 01-02-2014
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Peanut (Arachis hypogaea L.) is an important crop grown worldwide for food and edible oil. The surge of peanut allergy in the past 25 years has profoundly impacted both affected individuals and the peanut and related food industries. In response, several strategies to mitigate peanut allergy have emerged to reduce/eliminate the allergenicity of peanuts or to better treat peanut-allergic individuals. In this review, we give an overview of peanut allergy, with a focus on peanut proteins, including the impact of thermal processing on peanut protein structure and detection in food matrices. We discuss several strategies currently being investigated to mitigate peanut allergy, including genetic engineering, novel processing strategies, and immunotherapy in terms of mechanisms, recent research, and limitations. All strategies are discussed with considerations for both peanut-allergic individuals and the numerous industries/government agencies involved throughout peanut production and utilization.
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Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in A?1-42 insult in vitro.
PLoS ONE
PUBLISHED: 01-01-2014
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This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used A?1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to A?1-42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from A?1-42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.
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Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.
Neuro-oncology
PUBLISHED: 12-04-2013
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BackgroundTumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)-170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury.MethodsMice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique.ResultsRadiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor-? by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells.ConclusionsThe therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells.
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Allergenic properties of enzymatically hydrolyzed peanut flour extracts.
Int. Arch. Allergy Immunol.
PUBLISHED: 05-02-2013
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Peanut flour is a high-protein, low-oil, powdered material prepared from roasted peanut seed. In addition to being a well-established food ingredient, peanut flour is also the active ingredient in peanut oral immunotherapy trials. Enzymatic hydrolysis was evaluated as a processing strategy to generate hydrolysates from peanut flour with reduced allergenicity.
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Neurosurgery and prognosis in patients with radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy: a follow-up study.
Radiat Oncol
PUBLISHED: 03-20-2013
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Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain injury (RI). Treatment for RI remains a challenge. We conducted this study to investigate the indications of neurosurgery, operation time and prognosis of patients with RI after NPC radiotherapy who underwent neurosurgical management.
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Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold.
Liver Int.
PUBLISHED: 01-10-2013
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Hepatic tissue engineering is considered as a possible alternative to liver transplantation for end-stage liver disease. Several methods of decellularization of xenogeneic liver are available to produce three-dimensional organ scaffolds for engineering liver tissues. However, rare studies have examined and compared the effectiveness of different methods on the structure and composition of intact decellularized liver extracellular matrix.
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No enhanced expression and infectivity of porcine endogenous retrovirus in primary porcine hepatocytes with chitosan nanofiber scaffold.
J Biomed Nanotechnol
PUBLISHED: 08-12-2011
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Our previous report suggested that chitosan nanofiber scaffold may find application in bioartificial livers for it could enhance the function of hepatocytes. This study was focused on its microbiological safety, that is, its influence on the expression and infectivity of porcine endogenous retrovirus (PERV) in primary porcine hepatocytes. Freshly isolated porcine hepatocytes were cultured with or without chitosan nanofiber scaffold (defined as Exp group and Ctr group) and porcine kidney 15 (PK15) cells were cultured as positive control (defined as PK15 group). The supernatant was removed and substituted with new culture media after 24 hours followed by collecting the media and cells 72 hours later. To quantitative analyze PERV in the supernatant, the PERV RNA and capsid protein gag p30 were detected by dilution technique and RT activity was determined by specific kits. As a result, PERV RNA level, capsid protein and RT activity were all of no significant difference between Exp group and Ctr group, but these indices of the Exp group and Ctr group were both significantly lower than the PK15 group. To determine the expressing level of PERV in the cells, PERV RNA and capsid protein in the cell lysate were detected by RT-PCR and western blot with the software measurement of band lightness. Similarly, there was no difference for the amount of PERV RNA and capsid protein between Exp group and Ctr group but there was a higher PERV RNA level in PK15 group with no significant difference in protein level. Besides, the in-vitro infectivity of the supernatant was tested by incubating the human embryonic kidney 293 (HEK293) cells, showing no infection. In conclusion, chitosan nanofiber scaffold did not change the low expression and infectivity of PERV in porcine hepatocytes and it was safe for application in bio-artificial livers.
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A potato pathogenesis-related protein gene, StPRp27, contributes to race-nonspecific resistance against Phytophthora infestans.
Mol. Biol. Rep.
PUBLISHED: 02-28-2011
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Late blight caused by Phytophthora infestans is the most important disease of potato. Many efforts have been made to understand molecular mechanism of the durable resistance to address the challenge raised by rapid evolution of the pathogen. A pathogenesis related protein (PR) gene StPRp27 was previously isolated from the potato leaves challenged by P. infestans. The sequence analysis and expression pattern reveal that StPRp27 may be associated with resistance to P. infestans. In present research, transient expression of StPRp27 in Nicotiana benthamiana enhanced resistance to P. infestans isolates 99189 and PY23 indicating its potential contribution to the disease resistance. These findings were also confirmed by over-expression of StPRp27 in potato cv. E-potato 3, which significantly slowed down the development of the disease after inoculation with a mixture of P. infestans races. Further, silencing of StPRp27 homologous genes in N. benthamiana harboring dominant Phytophthora resistance gene Rpi-blb1 or Rpi-blb2 showed no effects on the resistance triggered by these R genes. Our results suggest that StPRp27 contributes to a race-nonspecific resistance against P. infestans by inhibiting the disease development and has a potential use in selection and breeding for durable resistance to late blight.
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In vitro analysis of cryopreserved alginate-poly-L-lysine-alginate-microencapsulated human hepatocytes.
Liver Int.
PUBLISHED: 01-11-2010
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The availability of well-characterized human hepatocytes that can be frozen and thawed will be critical for cell therapy. We addressed whether human hepatocytes can recover after microencapsulated cryopreservation and investigated whether these cryopreserved microencapsulated hepatocytes can be used for clinical applications.
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A simple isolation and cryopreservation method for adult human hepatocytes.
Int J Artif Organs
PUBLISHED: 11-28-2009
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The objective of this study was to establish a stable method of isolation, culture and cryopreservation of adult primary hepatocytes to provide potential hepatocyte resources for the treatment of acute and chronic liver diseases by hepatocyte transplantation and bioartificial liver support systems, and for the use of hepatocytes as an in vitro model of the liver.
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Contribution of bone marrow mesenchymal stem cells to porcine hepatocyte culture in vitro.
Biochem. Cell Biol.
PUBLISHED: 09-22-2009
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One of the greatest challenges in the attempt to create functional bioartificial liver designs is the maintenance of porcine hepatocyte differentiated functions in vitro. Co-cultivation of hepatocytes with nonparenchymal cells may be beneficial for optimizing cell functions via mimicry of physiological microenvironment. However, the underlying mechanisms remain to be elucidated. An equal number of freshly isolated porcine hepatocytes and purified bone marrow mesenchymal stem cells (MSCS) was randomly co-cultured and the morphological and functional changes of heterotypic interactions were characterized. Furthermore, contributions of soluble factors involved in the separated co-culture system were evaluated. The purity of the third-passage MSCS and primary hepatocytes was more than 90% and 99%, respectively. Hepatocyte viability was greater than 95%. A rapid attachment and self-organization of three-dimensional hepatocyte spheroids were encouraged, which was due to the supporting MSCS of high motility. The elevated induction of both albumin production and urea synthesis was achieved in co-culture (P < 0.05). Data from semipermeable membrane cultures suggested that interleukin-6 is one of the key stimulators in hepatic functional enhancement. These results demonstrate for the first time that soluble factors have beneficial effects on the preservation of hepatic morphology and functionality in the co-culture of hepatocytes with MSCS in vitro, which could represent a promising tool for tissue engineering, cell biology, and bioartificial liver devices.
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Heterotypic interactions in the preservation of morphology and functionality of porcine hepatocytes by bone marrow mesenchymal stem cells in vitro.
J. Cell. Physiol.
PUBLISHED: 02-28-2009
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Temporary replacement of specific liver functions with extracorporeal bioartificial liver has been hampered by rapid de-differentiation of porcine hepatocytes in vitro. Co-cultivation of hepatocytes with non-parenchymal cells may be beneficial for optimizing cell functions via mimicry of physiological microenvironment consisting of endogenous matrix proteins. However, the underlying mechanisms remain to be elucidated. A randomly distributed co-culture system composed of porcine hepatocytes and bone marrow mesenchymal stem cells was generated, and the morphological and functional changes of varying degrees of heterotypic interactions were characterized. Furthermore, contributions of extracellular matrix within this co-culture were evaluated. A rapid attachment and self-organization of three-dimensional hepatocyte spheroids were encouraged. Studies on hepatocyte viability showed a metabolically active, viable cell population in all co-culture configurations with occurrence of few dead cells. The maximal induction of albumin production, urea synthesis, and cytochrome P4503A1 activities was achieved at seeding ratio of 2:1. Immunocytochemical detection of various extracellular matrix confirmed that a high level of matrix proteins synthesis within distinct cells was involved in hepatocyte homeostasis. These results demonstrate for the first time that cell-matrix has synergic effects on the preservation of hepatic morphology and functionality in the co-culture of porcine hepatocytes with mesenchymal stem cells in vitro, which could represent a promising tool for tissue engineering, cell biology, and bioartificial liver devices.
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Establishment of a three-dimensional co-culture system by porcine hepatocytes and bone marrow mesenchymal stem cells in vitro.
Hepatol. Res.
PUBLISHED: 02-12-2009
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Aim: The application of porcine hepatocytes in liver support systems has been hampered by the short-term survival. Co-cultivation of hepatocytes with non-parenchymal cells may be beneficial for optimizing cell functions via heterotypic interactions. In this study, we present a new cultivation system of porcine hepatocytes and mesenchymal stem cells (MSCs) in a randomly distributed co-culture manner. Methods: Mononuclear cells were isolated from bone marrow aspirate of swines (n = 3) by density gradient centrifugation. MSCs were characterized by flow cytometry with CD29, CD44, CD45 and CD90, respectively. Then freshly isolated hepatocytes were simultaneously inoculated with MSCs in a hepatocyte dominant manner. The morphological and functional changes of heterotypic interactions were characterized. Results: Ninety percent MSCs of passage 3 were positive for CD29, CD44 and CD90, but negative for CD45. A rapid attachment and self-organization of three-dimensional hepatocyte aggregates were encouraged. The cell ultrastructure indicating heterotypic junctions remained similar to that of hepatocytes in vivo. Fluorescence microscopy further verified that MSCs served as a feeder layer for hepatocyte aggregates. Hepatocyte performance levels such as albumin secretion, urea synthesis and CYP3A1 induction were all significantly enhanced in co-culture group compared with hepatocyte homo-culture (P < 0.05). The best hepatic function levels were achieved on day 2 and moderately decreased in the following co-culture days. Moreover, the cell cycle of hepatocytes manifested the same trend in parallel to the enhancement of hepatocyte functionality. Conclusions: A three-dimensional co-culture system by porcine hepatocytes and bone marrow MSCs was for the first time established in vitro. Enhanced liver-specific functions make such a co-culture system a promising tool for tissue engineering, cell biology, and bioartificial liver devices.
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The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver function.
Biomaterials
PUBLISHED: 01-16-2009
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Liver tissue engineering requires a perfect extracellular matrix (ECM) for primary hepatocytes culture to maintain high level of liver-specific functions and desirable mechanical stability. The aim of this study was to develop a novel natural nanofibrous scaffold with surface-galactose ligands to enhance the bioactivity and mechanical stability of primary hepatocytes in culture. The nanofibrous scaffold was fabricated by electrospinning a natural material, galactosylated chitosan (GC), into nanofibers with an average diameter of approximately 160 nm. The GC nanofibrous scaffolds displayed slow degradation and suitable mechanical properties as an ECM for hepatocytes according to the evaluation of disintegration and Youngs modulus testing. The results of morphology characterization, double-staining fluorescence assay and function detection showed that hepatocytes cultured on GC nanofibrous scaffold formed stably immobilized 3D flat aggregates and exhibited superior cell bioactivity with higher levels of liver-specific function maintenance in terms of albumin secretion, urea synthesis and cytochrome P-450 enzyme than 3D spheroid aggregates formed on GC films. These spheroid aggregates could be detached easily during culture period from the flat GC films. We suggest such GC-based nanofibrous scaffolds could be useful for various applications such as bioartificial liver-assist devices and tissue engineering for liver regeneration as primary hepatocytes culture substrates.
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Clipping versus coiling for ruptured intracranial aneurysms: a systematic review and meta-analysis.
Stroke
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Endovascular treatment has increasingly been used for aneurismal subarachnoid aneurismal hemorrhage. The aim of this analysis is to assess the current evidence regarding safety and efficiency of clipping compared with coiling.
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Functional analysis of potato genes involved in quantitative resistance to Phytophthora infestans.
Mol. Biol. Rep.
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The most significant threat to potato production worldwide is the late blight disease, which is caused by the oomycete pathogen Phytophthora infestans. Based on previous cDNA microarrays and cDNA-amplified fragment length polymorphism analysis, 63 candidate genes that are expected to contribute to developing a durable resistance to late blight were selected for further functional analysis. We performed virus-induced gene silencing (VIGS) to these candidate genes on both Nicotiana benthamiana and potato, subsequently inoculated detached leaves and assessed the resistance level. Ten genes decreased the resistance to P. infestans after VIGS treatment. Among those, a lipoxygenase (LOX; EC 1.13.11.12) and a suberization-associated anionic peroxidase affected the resistance in both N. benthamiana and potato. Our results identify genes that may play a role in quantitative resistance mechanisms to late blight.
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Characterization of differential cocaine metabolism in mouse and rat through metabolomics-guided metabolite profiling.
Drug Metab. Dispos.
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Rodent animal models have been widely used for studying neurologic and toxicological events associated with cocaine abuse. It is known that the mouse is more susceptible to cocaine-induced hepatotoxicity (CIH) than the rat. However, the causes behind this species-dependent sensitivity to cocaine have not been elucidated. In this study, cocaine metabolism in the mouse and rat was characterized through LC-MS-based metabolomic analysis of urine samples and were further compared through calculating the relative abundance of individual cocaine metabolites. The results showed that the levels of benzoylecgonine, a major cocaine metabolite from ester hydrolysis, were comparable in the urine from the mice and rats treated with the same dose of cocaine. However, the levels of the cocaine metabolites from oxidative metabolism, such as N-hydroxybenzoylnorecgonine and hydroxybenzoylecgonine, differed dramatically between the two species, indicating species-dependent cocaine metabolism. Subsequent structural analysis through accurate mass analysis and LC-MS/MS fragmentation revealed that N-oxidation reactions, including N-demethylation and N-hydroxylation, are preferred metabolic routes in the mouse, while extensive aryl hydroxylation reactions occur in the rat. Through stable isotope tracing and in vitro enzyme reactions, a mouse-specific ?-glucoside of N-hydroxybenzoylnorecgonine and a group of aryl hydroxy glucuronides high in the rat were identified and structurally elucidated. The differences in the in vivo oxidative metabolism of cocaine between the two rodent species were confirmed by the in vitro microsomal incubations. Chemical inhibition of P450 enzymes further revealed that different P450-mediated oxidative reactions in the ecgonine and benzoic acid moieties of cocaine contribute to the species-dependent biotransformation of cocaine.
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Lipidomic profiling reveals protective function of fatty acid oxidation in cocaine-induced hepatotoxicity.
J. Lipid Res.
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During cocaine-induced hepatotoxicity, lipid accumulation occurs prior to necrotic cell death in the liver. However, the exact influences of cocaine on the homeostasis of lipid metabolism remain largely unknown. In this study, the progression of subacute hepatotoxicity, including centrilobular necrosis in the liver and elevation of transaminase activity in serum, was observed in a three-day cocaine treatment, accompanying the disruption of triacylglycerol (TAG) turnover. Serum TAG level increased on day 1 of cocaine treatment but remained unchanged afterwards. In contrast, hepatic TAG level was elevated continuously during three days of cocaine treatment and was better correlated with the development of hepatotoxicity. Lipidomic analyses of serum and liver samples revealed time-dependent separation of the control and cocaine-treated mice in multivariate models, which was due to the accumulation of long-chain acylcarnitines together with the disturbances of many bioactive phospholipid species in the cocaine-treated mice. An in vitro function assay confirmed the progressive inhibition of mitochondrial fatty acid oxidation after the cocaine treatment. Cotreatment of fenofibrate significantly increased the expression of peroxisome proliferator-activated receptor ? (PPAR?)-targeted genes and the mitochondrial fatty acid oxidation activity in the cocaine-treated mice, resulting in the inhibition of cocaine-induced acylcarnitine accumulation and other hepatotoxic effects. Overall, the results from this lipidomics-guided study revealed that the inhibition of fatty acid oxidation plays an important role in cocaine-induced liver injury.
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Psychological disorders, cognitive dysfunction and quality of life in nasopharyngeal carcinoma patients with radiation-induced brain injury.
PLoS ONE
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To evaluate factors affecting psychology, cognitive function and quality of life (QOL) of nasopharyngeal carcinoma (NPC) patients with radiation-induced brain injury (RI).
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Identification of N-acetyltaurine as a novel metabolite of ethanol through metabolomics-guided biochemical analysis.
J. Biol. Chem.
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The influence of ethanol on the small molecule metabolome and the role of CYP2E1 in ethanol-induced hepatotoxicity were investigated using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics platform and Cyp2e1-null mouse model. Histological and biochemical examinations of ethanol-exposed mice indicated that the Cyp2e1-null mice were more resistant to ethanol-induced hepatic steatosis and transaminase leakage than the wild-type mice, suggesting CYP2E1 contributes to ethanol-induced toxicity. Metabolomic analysis of urinary metabolites revealed time- and dose-dependent changes in the chemical composition of urine. Along with ethyl glucuronide and ethyl sulfate, N-acetyltaurine (NAT) was identified as a urinary metabolite that is highly responsive to ethanol exposure and is correlated with the presence of CYP2E1. Subsequent stable isotope labeling analysis using deuterated ethanol determined that NAT is a novel metabolite of ethanol. Among three possible substrates of NAT biosynthesis (taurine, acetyl-CoA, and acetate), the level of taurine was significantly reduced, whereas the levels of acetyl-CoA and acetate were dramatically increased after ethanol exposure. In vitro incubation assays suggested that acetate is the main precursor of NAT, which was further confirmed by the stable isotope labeling analysis using deuterated acetate. The incubations of tissues and cellular fractions with taurine and acetate indicated that the kidney has the highest NAT synthase activity among the tested organs, whereas the cytosol is the main site of NAT biosynthesis inside the cell. Overall, the combination of biochemical and metabolomic analysis revealed NAT is a novel metabolite of ethanol and a potential biomarker of hyperacetatemia.
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Radiofrequency Ablation Versus Hepatic Resection for Small Hepatocellular Carcinoma: A Meta-analysis of Randomized Controlled Trials.
J. Clin. Gastroenterol.
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Whether radiofrequency ablation or hepatic resection is superior for improving the survival in patients with small hepatocellular carcinoma (HCC) remains controversial. A meta-analysis of randomized controlled trials was performed to examine this issue.
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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.

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