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Find video protocols related to scientific articles indexed in Pubmed.
Role of Spinal CXCL1 (GRO?) in Opioid Tolerance: A Human-to-rodent Translational Study.
Anesthesiology
PUBLISHED: 11-11-2014
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The pivotal role of glial activation and up-regulated inflammatory mediators in the opioid tolerance has been confirmed in rodents but not yet in humans. Here, the authors investigated the intraspinal cytokine and chemokine profiles of opioid-tolerant cancer patients; and to determine if up-regulated chemokines could modify opioid tolerance in rats.
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New six- and seven-membered ring pyrrole-pyridine hydrogen bond systems undergoing excited-state intramolecular proton transfer.
Chem. Commun. (Camb.)
PUBLISHED: 10-21-2014
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New molecules, and , possessing six- and seven-membered ring pyrrole-pyridine hydrogen bonds, respectively, are designed and synthesized, which undergo excited-state intramolecular proton transfer with distinct reaction dynamics.
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A novel fusidic acid resistance determinant, fusF, in Staphylococcus cohnii.
J. Antimicrob. Chemother.
PUBLISHED: 10-15-2014
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To determine MICs of fusidic acid for and identify genetic determinants of resistance in Staphylococcus cohnii isolates.
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Antimicrobial Effect of Continuous Lidocaine Infusion in a Staphylococcus aureus-Induced Wound Infection in a Mouse Model.
Ann Plast Surg
PUBLISHED: 10-14-2014
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Continuous infusion of local anesthetics in surgical wounds has been shown to be an effective technique for postoperative analgesia. To investigate the potential antimicrobial effect of continuous local anesthetic infusion, we adapted a mouse model of surgical wound infection to examine effects on antibacterial response. Forty male BALB/c mice were randomized into 2 groups. An incision wound was made over the dorsal flank and instilled with Staphylococcus aureus. An osmotic pump was then implanted to deliver either 0.9% NaCl or 2% lidocaine continuously. Each wound was cultured postoperatively at 2 days, and the colony count of S. aureus was determined. Results showed that the number of colony-forming units of S. aureus measured in wounds treated with lidocaine displayed a nearly 10-fold reduction compared to the wounds in the saline group (P = 0.009). The demonstrated antibacterial activity indicates that local anesthetic infusion may play a role in prophylaxis for surgical wound infections.
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A High Efficiency Induction of Dopaminergic Cells from Human Umbilical Mesenchymal Stem Cells for the Treatment of Hemiparkinsonian Rats.
Cell Transplant
PUBLISHED: 10-08-2014
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Background The success rate in previous attempts at transforming human mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord to dopaminergic cells was a mere 12.7 %. The present study was therefore initiated to establish a more effective procedure for better yield of dopaminergic cells in such transformation for more effective HUMSC-based therapy for Parkinsonism. Methods To examine, in vitro, the effects of enhanced Nurr1 expression in HUMSCs on their differentiation, cells were processed through the three-stage differentiation protocol. The capacity of such cells to synthesize and release dopamine was measured by HPLC. The therapeutic effects of Nurr1-overexppressed HUMSCs were examined in 6-hydroxydopamine-lesioned rats by quantification of rotations in response to amphetamine. Results Enhanced Nurr1 expression in HUMSCs promoted the transformation into dopaminergic cells in vitro through stepwise culturing in sonic hedgehog, and fibroblast growth factor-8, neuron-conditioned medium. The success rate was about 71%, as determined by immunostaining for tyrosine hydroxylase, and around 94 nM dopamine synthesis (intracellular and released into the culture medium), as measured by HPLC. Additionally, transplantation of such cells into the striatum of hemiparkinsonian rats resulted in improvement of their behavioral deficits, as indicated by amphetamine-evoked rotation scores. Viability of the transplanted cells lasted for at least 3 months as verified by positive staining for tyrosine hydroxylase. Conclusions Nurr1, FGF8, Shh and NCM can synergistically enhance the differentiation of HUMSCs into dopaminergic cells, and may pave the way for HUMSCs-based treatments for Parkinson's disease.
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A smart and versatile theranostic nanomedicine platform based on nanoporphyrin.
Nat Commun
PUBLISHED: 08-26-2014
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Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. However, attaining consistently high performance of these functions in vivo in one single nanoconstruct remains extremely challenging. Here we demonstrate the use of one single polymer to develop a smart 'all-in-one' nanoporphyrin platform that conveniently integrates a broad range of clinically relevant functions. Nanoporphyrins can be used as amplifiable multimodality nanoprobes for near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), positron emission tomography (PET) and dual modal PET-MRI. Nanoporphyrins greatly increase the imaging sensitivity for tumour detection through background suppression in blood, as well as preferential accumulation and signal amplification in tumours. Nanoporphyrins also function as multiphase nanotransducers that can efficiently convert light to heat inside tumours for photothermal therapy (PTT), and light to singlet oxygen for photodynamic therapy (PDT). Furthermore, nanoporphyrins act as programmable releasing nanocarriers for targeted delivery of drugs or therapeutic radio-metals into tumours.
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High body mass index reduces glomerular filtration rate decline in type II diabetes mellitus patients with stage 3 or 4 chronic kidney disease.
Medicine (Baltimore)
PUBLISHED: 08-08-2014
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Whether high body mass index (BMI) has an effect on progressive diabetic nephropathy in type II diabetes mellitus (DM) patients with chronic kidney disease (CKD) stage 3 or 4 remains unclear. This prospective study aimed to investigate the relationship between BMI and progression of renal function deterioration in type II DM patients with CKD stage 3 or 4.A total of 105 type II DM patients with CKD stage 3 or 4 participated in this 24-month prospective observational study. Patients were divided into 3 groups according to BMI as follows: normal group, BMI of 18.5-22.9 kg/m; overweight group, BMI of 23-24.9 kg/m; and obese group, BMI of ?25 kg/m. The primary end point was a 2-fold elevation in serum creatinine levels (measured twice with a 1-month interval) from baseline values, need for long-term dialysis, or death during the 24-month observation period.In the linear regression analysis with the stepwise method, each 1 kg/m increase in BMI led to an increase of 0.32 mL min × 1.73 m in the estimated glomerular filtration rate (95% confidence interval, CI, 0.01-0.62; P = 0.04) during the 24-month study period. Moreover, multivariate Cox regression analysis showed that compared with the obese group, the normal BMI group (hazard ratio = 2.76, 95% CI : 1.27-6; P = 0.01) achieved the primary outcome after adjusting for other factors.In this 24-month prospective observational study, we showed that BMI of ?25 kg/m was a protective factor for renal function deterioration in type II DM patients with CKD stage 3 or 4.
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Locked ortho- and para-core chromophores of green fluorescent protein; dramatic emission enhancement via structural constraint.
J. Am. Chem. Soc.
PUBLISHED: 08-07-2014
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We report the design strategy and synthesis of a structurally locked GFP core chromophore p-LHBDI, its ortho-derivative, o-LHBDI, and H2BDI possessing both para- and ortho-hydroxyl groups such that the inherent rotational motion of the titled compounds has been partially restricted. o-LHBDI possesses a doubly locked configuration, i.e., the seven-membered ring hydrogen bond and five-membered ring C(4-5-10-13-14) cyclization, from which the excited-state intramolecular proton transfer takes place, rendering a record high tautomer emission yield (0.18 in toluene) and the generation of amplified spontaneous emission. Compared with their unlocked counterparts, a substantial increase in the emission yield is also observed for p-LHBDI and H2BDI in anionic forms in water, and accordingly the structure versus luminescence relationship is fully discussed based on their chemistry and spectroscopy aspect. In solid, o-LHBDI exhibits an H-aggregate-like molecular packing, offers narrow-bandwidth emission, and has been successfully applied to fabricate a yellow organic light emitting diodes (?max = 568 nm, ?ext = 1.9%) with an emission full width at half-maximum as narrow as 70 nm.
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trans/cis-Isomerization of Fluorene-Bridged Azo Chromophore with Significant Two-Photon Absorbability at Near-Infrared Wavelength.
Chem Asian J
PUBLISHED: 07-29-2014
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Azo-containing materials have been proven to possess second-order nonlinear optical (NLO) properties, but their third-order NLO properties, which involves two-photon absorption (2PA), has rarely been reported. In this study, we demonstrate a significant 2PA behavior of the novel azo chromophore incorporated with bilateral diphenylaminofluorenes (DPAFs) as a ? framework. The electron-donating DPAF moieties cause a redshifted ?-?* absorption band centered at 470?nm, thus allowing efficient blue-light-induced trans-to-cis photoisomerization with a rate constant of 2.04×10(-1) ?min(-1) at the photostationary state (PSS). The open-aperture Z-scan technique that adopted a femtosecond (fs) pulse laser as excitation source shows an appreciably higher 2PA cross-section for the fluorene-derived azo chromophore than that for common azobenzene dyes at near-infrared wavelength (?ex =800?nm). Furthermore, the fs 2PA response is quite uniform regardless of the molecular geometry. On the basis of the computational modeling, the intramolecular charge-transfer (ICT) process from peripheral diphenylamines to the central azo group through a fluorene ? bridge is crucial to this remarkable 2PA behavior.
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Cyclooxygenase 2 inhibitor celecoxib inhibits glutamate release by attenuating the PGE2/EP2 pathway in rat cerebral cortex endings.
J. Pharmacol. Exp. Ther.
PUBLISHED: 07-21-2014
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The excitotoxicity caused by excessive glutamate is a critical element in the neuropathology of acute and chronic brain disorders. Therefore, inhibition of glutamate release is a potentially valuable therapeutic strategy for treating these diseases. In this study, we investigated the effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor that reduces the level of prostaglandin E2 (PGE2), on endogenous glutamate release in rat cerebral cortex nerve terminals (synaptosomes). Celecoxib substantially inhibited the release of glutamate induced by the K(+) channel blocker 4-aminopyridine (4-AP), and this phenomenon was prevented by chelating the extracellular Ca(2+) ions and by the vesicular transporter inhibitor bafilomycin A1. Celecoxib inhibited a 4-AP-induced increase in cytosolic-free Ca(2+) concentration, and the celecoxib-mediated inhibition of glutamate release was prevented by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ?-conotoxin MVIIC. However, celecoxib did not alter 4-AP-mediated depolarization and Na(+) influx. In addition, this glutamate release-inhibiting effect of celecoxib was mediated through the PGE2 subtype 2 receptor (EP2) because it was not observed in the presence of butaprost (an EP2 agonist) or PF04418948 [1-(4-fluorobenzoyl)-3-[[6-methoxy-2-naphthalenyl)methyl]-3-azetidinecarboxylic acid; an EP2 antagonist]. The celecoxib effect on 4-AP-induced glutamate release was prevented by the inhibition or activation of protein kinase A (PKA), and celecoxib decreased the 4-AP-induced phosphorylation of PKA. We also determined that COX-2 and the EP2 receptor are present in presynaptic terminals because they are colocalized with synaptophysin, a presynaptic marker. These results collectively indicate that celecoxib inhibits glutamate release from nerve terminals by reducing voltage-dependent Ca(2+) entry through a signaling cascade involving EP2 and PKA.
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Intraoperative Measurement of Fractional Flow Reserve in Off-Pump Coronary Artery Bypass: A Pilot Study.
Thorac Cardiovasc Surg
PUBLISHED: 07-17-2014
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Backgrounds?Fractional flow reserve of myocardium (FFRmyo) is a functional study of significant coronary artery stenosis, defined as the ratio of the pressure distal to the stenosis (poststenosis) divided by the pressure of aortic root (prestenosis). Instead of cath laboratory, we could measure it in operating room for off-pump coronary artery bypass (OPCAB) surgery and here shared our methods in the pilot study. Methods and Results?We used needles, catheters, and pressure tracing but without guidewires or fluoroscopy to measure FFRmyo during OPCAB. In February 2010, we conducted the pilot study and collected 32 anastomosis data from 10 patients. Without revising the anastomosis plans based on coronary angiographies, 24 FFRmyo of the 32 anastomoses (75%) were less than 0.75, which represented significant functional stenosis. The FFRmyo measurements did not lead to any adverse events. Conclusion?The measurement of fractional flow reserve in OPCAB is safe and feasible. It can serve as a functional assessment of coronary artery stenosis in adjuvant to conventional coronary angiography.
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Fabrication and sensing behavior of one-dimensional ZnO-Zn2GeO4 heterostructures.
Nanoscale Res Lett
PUBLISHED: 07-09-2014
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Well-crystalline one-dimensional ZnO-Zn2GeO4 (ZGO) heterostructures were successfully synthesized using a high-temperature solid-state reaction between the ZnO and Ge layers of ZnO-Ge core-shell nanostructures. The polycrystalline ZGO crystallites had a thickness in the range of 17 to 26 nm. The high-temperature solid-state reaction induced grooves and crystal defects on the surfaces of the ZGO crystallites. The sensors made from the ZnO-ZGO heterostructures exhibited a marked photocurrent response to UV light at room temperature and a gas sensing response to acetone gas at 325°C. The observed sensing properties are attributed to the rugged surface of the ZGO heterointerfaces between ZnO and ZGO, surface crystal defects of ZGO, and cross-linked contact regions of ZnO-ZGO.
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Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.
Biomaterials
PUBLISHED: 06-30-2014
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Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation.
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Production of Bacillus subtilis-fermented red alga Porphyra dentata suspension with fibrinolytic and immune-enhancing activities.
Biosci. Biotechnol. Biochem.
PUBLISHED: 06-23-2014
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The fermented marine alga Porphyra dentata suspension was tested for its fibrinolytic and immune-enhancing activities. An isolated Bacillus subtilis N2 strain was selected for its fibrinolytic activity on fibrin plates. After investigating the effects of biomass amounts of P. dentata powder in water, various additives including sugars, nitrogen-containing substances, lipids and minerals, and cultural conditions of temperature and agitation in flask, the highest fibrinolytic activity in the cultural filtrate was obtained by cultivating N2 strain in 3% (w/v) P. dentata powder suspension containing 1% peanut oil at 37 °C, 150 rpm for 48 h. A fermentor system was further established using the same medium with controlled pH value of 7.0 at 37 °C, 150 rpm, 2.0 vvm for 48 h for the best fibrinolytic activity. The fermented product also showed its immune-enhancing activity by increasing cell proliferation and stimulating the secretion of IL-1?, IL-6, and TNF-? in J774.1 cells.
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A critical care monitoring system for depth of anaesthesia analysis based on entropy analysis and physiological information database.
Australas Phys Eng Sci Med
PUBLISHED: 06-10-2014
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Diagnosis of depth of anaesthesia (DoA) plays an important role in treatment and drug usage in the operating theatre and intensive care unit. With the flourishing development of analysis methods and monitoring devices for DoA, a small amount of physiological data had been stored and shared for further researches. In this paper, a critical care monitoring (CCM) system for DoA monitoring and analysis was designed and developed, which includes two main components: a physiologic information database (PID) and a DoA analysis subsystem. The PID, including biologic data and clinical information was constructed through a browser and server model so as to provide a safe and open platform for storage, sharing and further study of clinical anaesthesia information. In the analysis of DoA, according to our previous studies on approximate entropy, sample entropy (SampEn) and multi-scale entropy (MSE), the SampEn and MSE were integrated into the subsystem for indicating the state of patients underwent surgeries in real time because of their stability. Therefore, this CCM system not only supplies the original biological data and information collected from the operating room, but also shares our studies for improvement and innovation in the research of DoA.
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N-Phenethyl caffeamide and photodamage: protecting skin by inhibiting type I procollagen degradation and stimulating collagen synthesis.
Food Chem. Toxicol.
PUBLISHED: 05-23-2014
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Skin is mainly damaged by genetic and environmental factors such as ultraviolet (UV) light and pollutants. UV light is a well-known factor that causes various types of skin damage and premature aging. Reactive oxygen species (ROS) are commonly involved in the pathogenesis of skin damage by activating the metalloproteinases that break down type I collagen. This study investigated the antioxidant and antiphotodamage activity and mechanisms of N-phenethyl caffeamide (K36) in human skin fibroblasts. The results indicated that K36 demonstrated strong 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, which dose-dependently reduced the production of UVB-induced intracellular ROS in human dermal fibroblasts. K36 prevented UVB-irradiation-induced type I collagen degradation by inhibiting the expression of matrix metalloproteins-1, -3, and -9 and the phosphorylation of mitogen-activated protein (MAP) kinases. Furthermore, K36 elevated collagen synthesis in skin fibroblasts by inhibiting UVB-induced Smad7 overexpression. K36 downregulated the expression of the transcription factor, activator protein-1 (AP-1). Our results indicated that K36 exhibited antioxidant properties and prevented skin collagen degradation caused by UV exposure and the stimulation of collagen synthesis, which suggests the potential use of K36 in preventing photodamage.
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Asthma and self-harm: A population-based cohort study in Taiwan.
J Psychosom Res
PUBLISHED: 05-20-2014
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Few studies have investigated the relationship between asthma and suicidality-related outcomes in the world. We sought to investigate the association between asthma and risk of non-fatal self-harm in a large national sample.
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Glycemic Control Outcomes by Gender in the Pay-for-Performance System: A Retrospective Database Analysis in Patients with Type 2 Diabetes Mellitus.
Int J Endocrinol
PUBLISHED: 05-04-2014
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Background. The purpose of this study was to investigate how the degree of glycemic control in patients with type 2 diabetes associated with lifestyle interventions as well as sociodemographic factors and further examine the differences by gender. Methods. This was a retrospective study using data collected from a diabetes quality improvement plan that began in 2002 in a medical center in Taiwan. Statistic analysis was used to determine the associations of sociodemographic data, lifestyle intervention, and treatment regimens with changes in HbA1c levels (between the initial visit and the latest follow-up measured level), and the differences were then sorted by the sex of the patients. Results. Our results showed that HbA1c averaged 7.50% for males and 7.80% for females at the initial visit, compared to levels averaging 7.50% for males and 7.70% for females at the most recent follow-up visit. There was no significant change (P = 0.541) in HbA1c in males, but there was a 0.10% (P = 0.384) reduction in females. The duration of the diabetes and medication regimen was associated with the decrease seen in the females. Conclusions. The results of these analyses provide important insights for policy makers to formulate healthcare policies related to chronic diseases or illnesses.
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Improved identification of multiple drugs of abuse and relative metabolites in urine samples using liquid chromatography/triple quadrupole mass spectrometry coupled with a library search.
Rapid Commun. Mass Spectrom.
PUBLISHED: 03-25-2014
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Although two multiple reaction monitoring (MRM) transitions per compound are used for identification performed using liquid chromatography/triple quadrupole mass spectrometry (LC/QqQ-MS/MS), differences in identification criteria among several regulations may lead to misidentification. We demonstrated that the use of two MRM transitions and product ion spectra improves compound identification.
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Changes in sexual function of women with refractory interstitial cystitis/bladder pain syndrome after intravesical therapy with a hyaluronic acid solution.
J Sex Med
PUBLISHED: 03-17-2014
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Intravesical instillation with a hyaluronic acid (HA) solution is an effective treatment for interstitial cystitis/bladder pain syndrome (IC/BPS), but its impact on sexual functioning of patients is not known.
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Nanomicelle formulation modifies the pharmacokinetic profiles and cardiac toxicity of daunorubicin.
Nanomedicine (Lond)
PUBLISHED: 03-17-2014
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Treatment with daunorubicin (DNR) in acute myeloid leukemia is moderately effective and associated with significant side effects, including cardiac toxicity. We recently developed a nanomicellar formulation of DNR that specifically targets acute myeloid leukemia stem cells.
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Enhancement of diabetic wound repair using biodegradable nanofibrous metformin-eluting membranes: in vitro and in vivo.
ACS Appl Mater Interfaces
PUBLISHED: 03-06-2014
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This work developed biodegradable nanofibrous drug-eluting membranes that provided sustained release of metformin for repairing wounds associated with diabetes. To prepare the biodegradable membranes, poly-d-l-lactide-glycolide (PLGA) and metformin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and were spun into nanofibrous membranes by electrospinning. An elution method and an HPLC assay were utilized to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. The biodegradable nanofibrous membranes released high concentrations of metformin for more than three weeks. Moreover, nanofibrous metformin-eluting PLGA membranes were more hydrophilic and had a greater water-containing capacity than virgin PLGA fibers. The membranes also improved wound healing and re-epithelialization in diabetic rats relative to the control. The experimental results in this work suggest that nanofibrous metformin-eluting membranes were functionally active in the treatment of diabetic wounds and very effective as accelerators in the early stage of healing of such wounds.
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Toward efficient and omnidirectional n-type Si solar cells: concurrent improvement in optical and electrical characteristics by employing microscale hierarchical structures.
ACS Nano
PUBLISHED: 03-06-2014
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We demonstrated that hierarchical structures combining different scales (i.e., pyramids from 1.5 to 7.5 ?m in width on grooves from 40 to 50 ?m in diameter) exhibit excellent broadband and omnidirectional light-trapping characteristics. These microscaled hierarchical structures could not only improve light absorption but prevent poor electrical properties typically observed from nanostructures (e.g., ultra-high-density surface defects and nonconformal deposition of following layers, causing low open-circuit voltages and fill factors). The microscaled hierarchical Si heterojunction solar cells fabricated with hydrogenated amorphous Si layers on as-cut Czochralski n-type substrates show a high short-circuit current density of 36.4 mA/cm(2), an open-circuit voltage of 607 mV, and a conversion efficiency of 15.2% due to excellent antireflection and light-scattering characteristics without sacrificing minority carrier lifetimes. Compared to cells with grooved structures, hierarchical heterojunction solar cells exhibit a daily power density enhancement (69%) much higher than the power density enhancement at normal angle of incidence (49%), demonstrating omnidirectional photovoltaic characteristics of hierarchical structures. Such a concept of hierarchical structures simultaneously improving light absorption and photocarrier collection efficiency opens avenues for developing large-area and cost-effective solar energy devices in the industry.
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Incidence and risk of venous thromboembolism among Taiwan osteoporotic fracture population under osteoporosis pharmacological treatments.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-25-2014
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There was no clear evidence for the association between oral bisphosphonates or raloxifene and venous thromboembolism (VTE). There might also be ethnic differences in VTE risk.
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Irritant contact dermatitis risk of common topical traditional chinese medicines used for skin-lightening: a pilot clinical trial with 30 volunteers.
Evid Based Complement Alternat Med
PUBLISHED: 02-24-2014
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Topical traditional Chinese medicine- (TTCM-) related contact dermatitis is not uncommon but ignored. Patch and photopatch tests using 6 individual herbal ingredients and Bai-Zhi-Kao (BZK; ), a skin-lightening TTCM preparation, were conducted on 30 participants. Twenty-five subjects showed at least 1 positive reaction, including 6 (20.0%) participants who reacted to BZK. The majority reacted to Radix Ampelopsis japonica (Bai-Lian; ) (60.0%), whereas few reacted to Rhizoma Bletilla striata (Bai-Ji; ) (16.7%), Rhizoma Atractylodis macrocephalae (Bai-Zhu; ) (10.0%), Radix Angelicae dahuricae (Bai-Zhi; ) (3.3%), and Herba asari (Xi-Xin; ) (3.3%). In the photopatch test, 3 participants (10.0%) reacted positively to BZK and 10 to ?1 constituent; however, all reacted to Radix Angelicae dahuricae (26.7%), Radix Ampelopsis japonica (13.3%), and Rhizoma Bletilla striata (3.3%). In contrast, no subjects showed positive reactions to Sclerotium Poria cocos (Bai-Fu-Ling; ). Thus, BZK and its constituents might present potential latent risk of contact dermatitis owing to the possible presence of Radix Ampelopsis japonica and Radix Angelicae dahuricae. Furthermore, TTCMs, particularly cosmetic products, must be used carefully, with ample warning of potential contact dermatitis risk.
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Synthesis and characterization of two-photon chromophores based on a tetrasubstituted tetraethynylethylene scaffold.
Chem Asian J
PUBLISHED: 02-20-2014
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A new series of model dye molecules composed of three multibranched analogues based on the tetrasubstituted tetraethynylethylene structural motif have been synthesized and experimentally shown to possess strong and widely dispersed two-photon absorption (2PA) in the near-IR region. It was found that the spectral position of the major 2PA band could be tuned by the electronic nature of the selected substitution units. The studied model fluorophores also exhibited fairly low photodegradation of their fluorescence intensity even under prolonged UV-light irradiation, which is beneficial for the development of fluorescence probes that are needed for long-term light exposure. Furthermore, representative chromophores were selected to demonstrate the power-control properties within the femtosecond and nanosecond time domains.
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The wedelolactone derivative inhibits estrogen receptor-mediated breast, endometrial, and ovarian cancer cells growth.
Biomed Res Int
PUBLISHED: 02-13-2014
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Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers. Attenuating ER activities by natural products and their derivatives is a relatively practical strategy to control and reduce breast, endometrial, and ovarian cancer risk. Here, we found 3-butoxy-1,8,9-trihydroxy-6H-benzofuro[3,2-c]benzopyran-6-one (BTB), a new derivative of wedelolactone, could effectively inhibit the 17-estradiol (E2)-induced ER transactivation and suppress the growth of breast cancer as well as endometrial and ovarian cancer cells. Our results indicate that 2.5??M BTB effectively suppresses ER-positive, but not ER-negative, breast, endometrial, and ovarian cancer cells. Furthermore, our data indicate that BTB can modulate ER transactivation and suppress the expression of E2-mediated ER target genes (Cyclin D1, E2F1, and TERT) in the ER-positive MCF-7, Ishikawa, and SKOV-3 cells. Importantly, this BTB mediated inhibition of ER activity is selective since BTB does not suppress the activities of other nuclear receptors, including glucocorticoid receptor and progesterone receptor, suggesting that BTB functions as a selective ER signaling inhibitor with the potential to treat breast, endometrial, and ovarian cancers.
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Hybrid organic-inorganic heterojunction solar cells with 12% efficiency by utilizing flexible film-silicon with a hierarchical surface.
Nanoscale
PUBLISHED: 02-13-2014
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This paper reports an organic-inorganic hybrid solar cell with a hierarchical surface composed of high density silicon nanoholes and micro-desert textures. High-efficiency organic-inorganic hybrid solar cell Si/PEDOT-PSS with a hierarchical surface, showing a power conversion efficiency of 12%. The structure provides excellent light absorption over 97% for the spectral range of 300 to 1100 nm with a thickness of 60 ?m due to internal multiple reflections caused by subwavelength features of high density silicon nanoholes and micro-desert textures. In addition, from the angle of incidence (AOI) observed, even at the large angle of 75°, the reflectance value still exhibits less than 1%. With the advantage of very thin silicon material and inexpensive processing, hybrid silicon/polymer solar cells are promising for various applications and thus could be an economically feasible alternative energy solution in the future.
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Exposure of polyethylene particles induces interferon-? expression in a natural killer T lymphocyte and dendritic cell coculture system in vitro: A preliminary study.
J Biomed Mater Res A
PUBLISHED: 02-12-2014
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Two major issues in total joint arthroplasty are loosening of implants and osteolysis caused by wear particle-induced inflammation. Wear particles stimulate the release of pro-inflammatory cytokines, chemokines, and other inflammatory mediators from macrophages and other cells. Although the biological response of macrophages to wear debris is well established, the role of other cell types such as natural killer T lymphocytes (NKT) and dendritic cells (DCs) is limited. Here we show that ultra-high molecular weight polyethylene (UHMWPE) particles stimulate NKT cells to secrete Interferon-? (IFN-?); coculture with DCs further enhanced IFN-? secretion. Furthermore, UHMWPE particles did not stimulate NKT cells to secrete IL-4, while the NKT cell natural ligand ?-galactosylceramide (?-GalCer) treatment in the coculture system significantly enhanced both IFN-? and IL-4 expression by NKT cells. Comparatively, NKT cells and/or DCs exposed to polymethylmethacrylate particles did not stimulate IFN-? or IL-4 expression. Mouse bone marrow derived macrophage polarization by lipopolysaccharide and conditioned medium from NKT cells and/or DCs exposed to UHMWPE particles increased tumor necrosis factor-? (TNF-?), but reduced arginase-1 expression in macrophages. The current findings indicate that UHMWPE particles stimulate NKT cells/DCs to produce pro-inflammatory cytokines; this pathway is a novel therapeutic target to mitigate wear particle induced peri-prosthetic osteolysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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Overexpression of miR-9 in mast cells is associated with invasive behavior and spontaneous metastasis.
BMC Cancer
PUBLISHED: 01-27-2014
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While microRNA (miRNA) expression is known to be altered in a variety of human malignancies contributing to cancer development and progression, the potential role of miRNA dysregulation in malignant mast cell disease has not been previously explored. The purpose of this study was to investigate the potential contribution of miRNA dysregulation to the biology of canine mast cell tumors (MCTs), a well-established spontaneous model of malignant mast cell disease.
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Suppression of wear-particle-induced pro-inflammatory cytokine and chemokine production in macrophages via NF-?B decoy oligodeoxynucleotide: a preliminary report.
Acta Biomater
PUBLISHED: 01-15-2014
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Total joint replacement (TJR) is very cost-effective surgery for end-stage arthritis. One important goal is to decrease the revision rate, mainly because TJR has been extended to younger patients. Continuous production of ultra-high molecular weight polyethylene (UHMWPE) wear particles induces macrophage infiltration and chronic inflammation, which can lead to periprosthetic osteolysis. Targeting individual pro-inflammatory cytokines directly has not reversed the osteolytic process in clinical trials, owing to compensatory up-regulation of other pro-inflammatory factors. It is hypothesized that targeting the important transcription factor NF-?B could mitigate the inflammatory response to wear particles, potentially diminishing osteolysis. In the current study, NF-?B activity in mouse RAW 264.7 and human THP1 macrophage cell lines, as well as primary mouse and human macrophages, was suppressed via competitive binding with double strand decoy oligodeoxynucleotide (ODN) containing an NF-?B binding element. It was found that macrophage exposure to UHMWPE particles induced multiple pro-inflammatory cytokine and chemokine expression, including TNF-?, MCP1, MIP1? and others. Importantly, the decoy ODN significantly suppressed the induced cytokine and chemokine expression in both murine and human macrophages, and resulted in suppression of macrophage recruitment. The strategic use of decoy NF-?B ODN, delivered locally, could potentially diminish particle-induced periprosthetic osteolysis.
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Association between blood cadmium levels and malnutrition in peritoneal dialysis.
BMC Nephrol
PUBLISHED: 01-11-2014
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Malnutrition is associated with an increased risk of cardiovascular death and may cause protein-energy wasting in individuals with chronic kidney disease. A previous study demonstrated that blood cadmium levels (BCLs) were associated with malnutrition in maintenance hemodialysis (MHD) patients. However, the correlation between cadmium exposure and malnutrition remains unclear in chronic peritoneal dialysis (CPD) patients. This study examined the possible adverse effects of environmental cadmium exposure in CPD patients.
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Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps.
J Biomed Mater Res A
PUBLISHED: 01-03-2014
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Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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A Rapid Method of Detecting Autoantibody against Fc?RI? for Chronic Spontaneous Urticaria.
PLoS ONE
PUBLISHED: 01-01-2014
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Chronic spontaneous urticaria (CU) is a common skin disorder, with an estimated prevalence of 0.5-1.8% in most populations. Around 30-50% of CU patients have an autoimmune etiology, with autoantibodies (autoAbs) against IgE, Fc?RI?, and Fc?RII/CD23. Although the in vivo autologous serum skin test (ASST) and in vitro histamine release/activation assay are the most frequently used screening methods, these two have many limitations and do not directly measure susceptible autoAbs. This study aimed to establish an in vitro rapid screening test using recombinant autoantigen Fc?RI?(rFc?RI?) to improve the diagnosis of autoimmune urticaria.
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Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers.
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5-Lipoxygenase inhibitors attenuate TNF-?-induced inflammation in human synovial fibroblasts.
PLoS ONE
PUBLISHED: 01-01-2014
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The lipoxygenase isoform of 5-lipoxygenase (5-LOX) is reported to be overexpressed in human rheumatoid arthritis synovial tissue and involved in the progress of inflammatory arthritis. However, the detailed mechanism of how 5-lipoxygenase regulates the inflammatory response in arthritis synovial tissue is still unclear. The aim of this study was to investigate the involvement of lipoxygenase pathways in TNF-?-induced production of cytokines and chemokines. Human synovial fibroblasts from rheumatoid patients were used in this study. 5-LOX inhibitors and shRNA were used to examine the involvement of 5-LOX in TNF-?-induced cytokines and chemokines expression. The signaling pathways were examined by Western Blotting or immunofluorescence staining. The effect of 5-LOX inhibitor on TNF-?-induced chemokine expression and paw edema was also explored in vivo in C57BL/6 mice. Treatment with 5-LOX inhibitors significantly decreased TNF-?-induced pro-inflammatory mediators including interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) in human synovial fibroblasts. Knockdown of 5-LOX using shRNA exerted similar inhibitory effects. The abrogation of NF-?B activation was involved in the antagonizing effects of these inhibitors. Furthermore, 5-LOX inhibitor decreased TNF-?-induced up-regulation of serum MCP-1 level and paw edema in mouse model. Our results provide the evidence that the administration of 5-LOX inhibitors is able to ameliorate TNF-?-induced cytokine/chemokine release and paw edema, indicating that 5-LOX inhibitors may be developed for therapeutic treatment of inflammatory arthritis.
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Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L.) Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes) was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+) concentration ([Ca(2+)]C) in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker known as ?-conotoxin MVIIC. In a kainic acid (KA) rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg) was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg) intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+) entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.
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A Novel Staphylococcal Cassette Chromosomal Element, SCCfusC, Carrying fusC and speG in Fusidic Acid-Resistant Methicillin-Resistant Staphylococcus aureus.
Antimicrob. Agents Chemother.
PUBLISHED: 11-25-2013
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The high prevalence of fusC (16/46, 59%) was found in fusidic acid-resistant methicillin-resistant Staphylococcus aureus isolates collected from 2008 to 2010. Nucleotide sequencing of fusC and flanking regions revealed a novel SCC structure, SCCfusC, which was integrated into rlmH and located upstream of SCCmec. The SCCfusC element contained speG, which may contribute to the polyamine resistance.
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Comparative effectiveness of osteoporosis drugs in preventing secondary nonvertebral fractures in taiwanese women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-30-2013
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Context: The evidence for relative effectiveness of osteoporosis drugs in secondary prevention of nonvertebral fractures was unclear and could not be extrapolated to the Asian population. Objective: The objective of the study was to compare the relative effectiveness of different classes of osteoporosis drugs in secondary prevention of nonvertebral fractures in Taiwanese women. Design: This was a retrospective cohort study from 2003 to 2007, with up to 6 years of follow-up. Setting: The study included enrollees in Taiwan National Health Insurance. Patients: Patients older than 50 years, with vertebral/hip fracture and were new to osteoporosis therapy, were recruited. Intervention: Patients were classified into the alendronate, calcitonin, or raloxifene group, according to their exposure after follow-up. Main Outcome Measure: The primary outcome of our study was the risk of incident nonvertebral fracture (hip, humerus, or radius fractures). A multivariate Cox proportional hazard model adjusted for fracture risk factors was used to compare the relative fracture risk among three treatment groups under on-treatment scenarios. Propensity score-matched hazard ratios were examined, and interactions between fracture incidence and patients compliance were investigated as well. Results: There were 19 840, 9534, and 25 483 patients in the alendronate, raloxifene, and calcitonin groups, respectively. The fracture rates were highest in calcitonin recipients (4.57 per 100 person-years), followed by raloxifene and alendronate. Results from Cox analyses showed raloxifene (hazard ratio 1.47; 95% confidence interval 1.29-1.67) and calcitonin (hazard ratio 1.51; 95% confidence interval 1.29-1.75) had higher nonvertebral fracture risks as compared with alendronate. The risk differences were more pronounced in compliant patients. Conclusion: We found alendronate users had the lowest secondary nonvertebral fracture risk, as compared with raloxifene and calcitonin users. Consistent results were found in a series of sensitivity analyses.
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Realizing high-efficiency omnidirectional n-type Si solar cells via the hierarchical architecture concept with radial junctions.
ACS Nano
PUBLISHED: 09-24-2013
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Hierarchical structures combining micropyramids and nanowires with appropriate control of surface carrier recombination represent a class of architectures for radial p-n junction solar cells that synergizes the advantageous features including excellent broad-band, omnidirectional light-harvesting and efficient separation/collection of photoexcited carriers. The heterojunction solar cells fabricated with hierarchical structures exhibit the efficiency of 15.14% using cost-effective as-cut Czochralski n-type Si substrates, which is the highest reported efficiency among all n-type Si nanostructured solar cells. We also demonstrate the omnidirectional solar cell that exhibits the daily generated power enhancement of 44.2% by using hierarchical structures, as compared to conventional micropyramid control cells. The concurrent improvement in optical and electrical properties for realizing high-efficiency omnidirectional solar cells using as-cut Czochralski n-type Si substrates demonstrated here makes a hierarchical architecture concept promising for large-area and cost-effective mass production.
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New structure of phage-related islands carrying fusB and a virulence gene in fusidic acid-resistant Staphylococcus epidermidis.
Antimicrob. Agents Chemother.
PUBLISHED: 08-26-2013
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Nucleotide sequencing of the fusB-flanking regions in two fusidic acid-resistant Staphylococcus epidermidis isolates with the type IV aj1-leader peptide (LP)-fusB structure (lacking aj1) revealed that their fusB gene was located on novel phage-related islands inserted downstream of smpB and are here referred to as SeRIfusB-3692 and SePIfusB-857. The novel SePIfusB-857 structure was followed by SeCI857, forming a composite pathogenicity island which contained a putative virulence gene, vapE. The linkage of fusB and vapE may contribute to bacterial adaption.
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Nematic molecular core flexibility and chiral induction.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 08-08-2013
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Electroclinic measurements, in which an applied electric field E induces a rotation ?? (?E) of the liquid crystal director about the electric field axis in a chiral environment, were performed on several configurationally achiral liquid crystals in the presence of an imposed helical director profile. This imposed twist establishes a chiral symmetry environment for the liquid crystal. It was observed that a conformationally racemic mesogen possessing a flexible phenyl benzoate core exhibits a measurable electroclinic response in the nematic phase. On the other hand, when the phenyl benzoate mesogen is mixed with a mesogen containing a rigid, conformationally achiral core (fluorenone), or with a racemic dopant with an axially chiral core that mimics a mesogen having rigid right- and left-handed conformations (2,2^{}-spirobiindan-1,1^{}-dione), the magnitudes of the electroclinic responses were found to decrease sharply, apparently going to zero when extrapolated to the pure 2,2^{}-spirobiindan-1,1^{}-dione or fluorenone limit. (Note that neither of these additives possesses a nematic phase.) The results suggest that the flexibility of the core and its ability to deracemize conformationally in order to compensate the elastic energy cost of the imposed twist is the primary mechanism behind the observed electroclinic response.
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Prenatal diagnosis of proximal femoral focal deficiency: a case report and literature review.
Taiwan J Obstet Gynecol
PUBLISHED: 08-07-2013
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To present a rare case of fetal nonfamilial proximal femoral focal deficiency (PFFD) diagnosed as early as 21 weeks gestation.
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Lethal fetal stroke in utero.
Taiwan J Obstet Gynecol
PUBLISHED: 08-07-2013
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Fetal intracranial hemorrhage (ICH) in utero is a rare complication of pregnancy associated with subsequent neurological sequelae or fetal death.
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Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-?B as a therapeutic target.
Acta Biomater
PUBLISHED: 07-31-2013
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Biomaterial-induced tissue responses in patients with total joint replacement are associated with the generation of wear particles, which may lead to chronic inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory reactions associated with wear particles are mediated by several important signaling pathways, the most important of which involves the transcription factor NF-?B. NF-?B activation is essential for macrophage recruitment and maturation, as well as the production of pro-inflammatory cytokines and chemokines such as TNF-?, IL-1?, IL-6 and MCP1. In addition, NF-?B activation contributes to osteoclast differentiation and maturation via RANK/RANKL signaling, which increases bone destruction and reduces bone formation. Targeting individual downstream cytokines directly (such as TNF-? or IL-1?) may not effectively prevent wear particle induced osteolysis. A more logical upstream therapeutic approach may be provided by direct modulation of the core I?B/IKK?/?/NF-?B signaling pathway in the local environment. However, the timing, dose and strategy for administration should be considered. Suppression of chronic inflammation via inhibition of NF-?B activity in patients with malfunctioning joint replacements may be an effective strategy to mitigate wear particle induced periprosthetic osteolysis.
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Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis.
Hepatology
PUBLISHED: 07-06-2013
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Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been considered as an alternative therapy, replacing liver transplantation in clinical trials, to treat liver cirrhosis, an irreversible disease that may eventually lead to liver cancer development. However, low survival rate of the BM-MSCs leading to unsatisfactory efficacy remains a major concern. Gender differences have been suggested in BM-MSCs therapeutic application, but the effect of the androgen receptor (AR), a key factor in male sexual phenotype, in this application is not clear. Using two liver cirrhosis mouse models induced by CCl4 or thioacetamide, we showed that targeting AR in the BM-MSCs improved their self-renewal and migration potentials and increased paracrine effects to exert anti-inflammatory and anti-fibrotic actions to enhance liver repair. Mechanism dissection studies suggested that knocking out AR in BM-MSCs led to improved self-renewal and migration by alteration of the signaling of epidermal growth factor receptor and matrix metalloproteinase 9 and resulted in suppression of infiltrating macrophages and hepatic stellate cell activation through modulation of interleukin (IL)1R/IL1Ra signaling. Therapeutic approaches using either AR/small interfering RNA or the AR degradation enhancer, ASC-J9, to target AR in BM-MSCs all led to increased efficacy for liver repair.
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Ethanol Extracts of Fresh Davallia formosana (WL1101) Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor- ? B Activation.
Evid Based Complement Alternat Med
PUBLISHED: 06-24-2013
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The rhizome of Davallia formosana is commonly used to treat bone disease including bone fracture, arthritis, and osteoporosis in Chinese herbal medicine. Here, we report the effects of WL1101, the ethanol extracts of fresh rhizomes of Davallia formosana on ovariectomy-induced osteoporosis. In addition, excess activated bone-resorbing osteoclasts play crucial roles in inflammation-induced bone loss diseases, including rheumatoid arthritis and osteoporosis. In this study, we examined the effects of WL1101 on receptor activator of nuclear factor- ? B ligand (RANKL)-induced osteoclastogenesis. Treatment with WL1101 significantly inhibited RANKL-stimulated osteoclastogenesis. Two isolated active compounds, ((-)-epicatechin) or WL14 (4-hydroxy-3-aminobenzoic acid) could also inhibit RANKL-induced osteoclastogenesis. WL1101 suppressed the RANKL-induced nuclear factor- ? B (NF- ? B) activation and nuclear translocation, which is the key process during osteoclastogenesis, by inhibiting the activation of I ? B kinase (IKK) and I ? B ? . In animal model, oral administration of WL1101 (50 or 200?mg/kg/day) effectively decreased the excess bone resorption and significantly antagonized the trabecular bone loss in ovariectomized rats. Our results demonstrate that the ethanol extracts of fresh rhizomes of Davallia formosana inhibit osteoclast differentiation via the inhibition of NF- ? B activation and effectively ameliorate ovariectomy-induced osteoporosis. WL1101 may thus have therapeutic potential for the treatment of diseases associated with excessive osteoclastic activity.
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Differential androgen deprivation therapies with anti-androgens casodex/bicalutamide or MDV3100/Enzalutamide versus anti-androgen receptor ASC-J9(R) Lead to promotion versus suppression of prostate cancer metastasis.
J. Biol. Chem.
PUBLISHED: 05-16-2013
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Despite the fact that androgen deprivation therapy (ADT) can effectively reduce prostate cancer (PCa) size, its effect on PCa metastasis remains unclear. We examined the existing data on PCa patients treated with ADT plus anti-androgens to analyze ADT effects on primary tumor size, prostate-specific antigen (PSA) values, and metastatic incidence. We found that the current ADT with anti-androgens might lead to primary tumor reduction, with PSA decreased yet metastases increased in some PCa patients. Using in vitro and in vivo metastasis models with four human PCa cell lines, we evaluated the effects of the currently used anti-androgens, Casodex/bicalutamide and MDV3100/enzalutamide, and the newly developed anti-AR compounds, ASC-J9® and cryptotanshinone, on PCa cell growth and invasion. In vitro results showed that 10 ?m Casodex or MDV3100 treatments suppressed PCa cell growth and reduced PSA level yet significantly enhanced PCa cell invasion. In vivo mice studies using an orthotopic xenograft mouse model also confirmed these results. In contrast, ASC-J9® led to suppressed PCa cell growth and cell invasion in in vitro and in vivo models. Mechanism dissection indicated these Casodex/MDV3100 treatments enhanced the TGF-?1/Smad3/MMP9 pathway, but ASC-J9® and cryptotanshinone showed promising anti-invasion effects via down-regulation of MMP9 expression. These findings suggest the potential risks of using anti-androgens and provide a potential new therapy using ASC-J9® to battle PCa metastasis at the castration-resistant stage.
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Offering acupuncture as an adjunct for tobacco cessation: a community clinic experience.
Health Promot Pract
PUBLISHED: 05-10-2013
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Disparities in smoking rates remain prominent within Asian Americans. Medical pluralism and cultural tailoring may enhance Asian Americans engaging with tobacco cessation assistance. We conducted a retrospective analysis of a community clinics smoking cessation program targeting a Chinese population that offered acupuncture, nicotine replacement therapy (NRT), and counseling from 2007 to 2010. Most participants used acupuncture, with about half choosing acupuncture and NRT, followed by more than 40% choosing acupuncture only; few chose NRT only. Tobacco cessation rates at 6 months were relatively high for the acupuncture + NRT group and only acupuncture group (37.7% vs. 28.9%). In comparing tobacco reduction >50% from baseline with an expanded only NRT group, the acupuncture + NRT group had a higher odds ratio than the only acupuncture group, which had a lower odds ratio. Our evaluation of this real-world community program offering acupuncture as a cultural adjunct to a tobacco cessation program suggests that acupuncture might help with engagement by Chinese American male smokers into a tobacco cessation program that offers counseling and NRT. Future larger studies should further evaluate the efficacy of offering acupuncture in combination with NRT on the outcomes of cessation and reduction.
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Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles.
J Biomed Mater Res A
PUBLISHED: 05-03-2013
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Wear particles generated from total joint replacements can stimulate macrophages to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which is the most important chemokine regulating systemic and local cell trafficking and infiltration of monocyte/macrophages in chronic inflammation. One possible strategy to curtail the adverse events associated with wear particles is to mitigate migration and activation of monocyte/macrophages. The purpose of this study is to modulate the adverse effects of particulate biomaterials and inflammatory stimuli such as endotoxin by interfering with the biological effects of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased MCP-1-induced migration of THP-1 cells in cell migration experiments in a dose-dependent manner. Conditioned media from murine macrophages exposed to clinically relevant polymethylmethacrylate (PMMA) particles with/without endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse effects on the viability of macrophages, and the capability of mesenchymal stem cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine production was mitigated when macrophages were exposed to PMMA particles with/without LPS in the presence of 7ND. Our studies confirm that the MCP-1 mutant protein 7ND can decrease macrophage migration and inflammatory cytokine release without adverse effects at the doses tested. Local delivery of 7ND at the implant site may provide a therapeutic strategy to diminish particle-associated periprosthetic inflammation and osteolysis. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Education level is associated with mortality in male patients undergoing maintenance hemodialysis.
Blood Purif.
PUBLISHED: 04-23-2013
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Studies of the correlation between education levels and mortality in hemodialysis (HD) patients are rare. The aim of this multi-center study was to investigate the relationship between education levels and 3-year mortality rates in HD patients.
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Enhancement of placenta growth factor expression by oncostatin M in human rheumatoid arthritis synovial fibroblasts.
J. Cell. Physiol.
PUBLISHED: 04-04-2013
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Oncostatin M (OSM) belongs to IL-6 subfamily and is mostly produced by T lymphocytes. High levels of OSM are detected in the pannus of rheumatoid arthritis (RA) patients and it may arouse the inflammation responses in joints and eventually leads to bone erosion. Placenta growth factor (PLGF) is an angiogenic factor and highly homologous with vascular endothelial growth factor (VEGF). It has been recently reported that PLGF is highly expressed in synovial tissue and enhances the production of proinflammatory cytokines including TNF-? and IL-6. Here, we demonstrated that OSM increased mRNA and protein levels of PLGF in a time- and concentration-dependent manner in RA synovial fibroblasts. Inhibitors of JAK3 and PI3K antagonized OSM-induced production of PLGF. OSM enhanced the phosphorylation of Tyr705-STAT3, Ser727-STAT3, Ser473-Akt, and increased the nuclear translocation of phosphorylated STAT3 time-dependently. Transfection of dominant negative Akt or application of PI3K inhibitorLY294002 significantly inhibited p-Tyr705-STAT3, p-Ser727-STAT3, and PLGF expression, indicating that Akt is involved in JAK3/STAT3/PLGF signaling cascade. To further examine whether STAT3 binds to the promoter region of PLGF, Chip assay was used and it was found that OSM could bind with PLGF promoter, which was inhibited by JAK3 and PI3K inhibitors. Accumulation of PLGF in the pannus may contribute to the inflammation, angiogenesis and joints destruction in RA patients. These findings demonstrated the important role of OSM in the pathology network of RA and provided novel therapeutic drug targets for RA treatment.
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The impact of body weight management in chronic kidney disease patients with obesity.
J Ren Nutr
PUBLISHED: 04-02-2013
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Chronic kidney disease (CKD) and obesity are important public health concerns. Because obesity may initiate and/or accelerate kidney damage, weight control may benefit CKD patients.
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Quercetin inhibits depolarization-evoked glutamate release in nerve terminals from rat cerebral cortex.
Neurotoxicology
PUBLISHED: 03-18-2013
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Quercetin, a naturally occurring flavonoid, has been reported to have a neuroprotective profile. An excessive release of glutamate is widely considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. This study investigated whether quercetin affected glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Quercetin inhibited the release of glutamate evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this effect was prevented by the chelating extracellular Ca(2+) ions. Quercetin decreased the depolarization-induced increase in the cytosolic free Ca(2+) concentration ([Ca(2+)]C), whereas it did not alter 4-AP-mediated depolarization and Na(+) influx. The quercetin-mediated inhibition of glutamate release was prevented by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release. Combined inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the inhibitory effect of quercetin on evoked glutamate release. Furthermore, quercetin decreased the 4-AP-induced phosphorylation of PKC and PKA. These results suggest that quercetin inhibits glutamate release from rat cortical synaptosomes and this effect is linked to a decrease in presynaptic voltage-dependent Ca(2+) entry and to the suppression of PKC and PKA activity.
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Simultaneous quantification of amphetamine, opiates, ketamine and relative metabolites in urine for confirmatory analysis by liquid chromatography tandem mass spectrometry.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 03-12-2013
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The rise in amphetamine, ketamine and opiates abuse in Taiwan has created a need for a reliable confirmatory assay. A method that combines superficially porous liquid chromatography tandem mass spectrometry (LC-MS/MS) with solid-phase extraction (SPE) was developed for the simultaneous quantification of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, opiates, and their corresponding metabolites in urine. The total run time of the method was 6.7min including equilibration time. The method was validated in accordance with the European Commission (EC) Decision 2002/642/EC. The within- and between-day precision was below 13.6% and the accuracy ranged from -17.1% to +9.9% for all analytes. Ion suppression was observed but compensated by using deuterated internal standards. No carryover was detected and the analytes were stable at room temperature for 16h, and for 72h at 4°C, and three-thaw cycles. The method was further validated by comparison with a reference gas chromatography-mass spectrometry (GC-MS) method, using 52 authentic urine samples. The results indicated that for the target analytes studied, the LC-MS/MS analysis was as precise, accurate, and specific as the GC-MS method. In conclusion, the present LC-MS/MS method is robust and reliable, and suitable for use as a confirmation assay in the simultaneous urine drug testing and quantification of amphetamines, ketamines, and opiates.
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Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines.
Biomaterials
PUBLISHED: 03-06-2013
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Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs) therapy. However, MSCs from different origins might exhibit distinct differentiation capacities. This study was undertaken to compare the therapeutic efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM-MSCs were first characterized. The coculture commitment system was subsequently utilized for comparing the patterned molecules in stage-specific chondrogenesis of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs and BM-MSCs were encapsulated in neo-cartilage and subjected into pro-inflammatory cytokine environment. Finally, chondrogenic and inflammatory cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both negative for hematopoietic markers and positive for adhesion and mesenchymal cell markers. The CB-MSCs showed a markedly higher chondrogenic potential and relatively lower osteogenic and adipogenic capacities than BM-MSCs. During chondrogenesis, the committed CB-MSCs also showed significant increases in cell proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific gene expressions in a coculture system. For the therapeutic efficacies, the committed CB-MSCs could strongly recover the pro-inflammatory cytokines diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL-10, ICAM-1 and TGF-?1 were also up-regulated in committed CB-MSCs analyzed by using cytokine profiling. Our data demonstrate that CB-MSCs possess specific advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better therapeutic potential that can contribute to advanced cell-based transplantation for clinical OA therapy.
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Cardioplegia delivery by transcutaneous pigtail catheter in minimally invasive mitral valve operations.
Ann. Thorac. Surg.
PUBLISHED: 02-27-2013
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For cardioplegia delivery and removing air from the aorta in minimally invasive mitral valve operations, we would like to propose a cost-effective pigtail method. The 8F pigtail punctures the aorta, delivers cardioplegia, and stays in place for removing air from the aorta. We then slide its tip out of the aorta as an accessory drain. With more than 100 successes, we are using it in every case and would like to share it with peer surgeons.
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Endovascular treatment for traumatic thoracic aortic pseudoaneurysm: a case report.
J Cardiothorac Surg
PUBLISHED: 02-25-2013
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Cases of an endovascular treatment for traumatic aortic injury are extremely rare. A prompt diagnosis of traumatic thoracic aortic pseudoaneurysm through a 3-dimensional computed tomographic angiography of aorta and emergency repair are mandatory to rescue the life-threatening condition. An endovascular treatment is a trend for traumatic aortic injury because of lower invasivity, morbidity and mortality. We reported a rare case of traumatic aortic injury with thoracic aortic pseudoaneurysm definitively diagnosed by the reconstructional computed tomographic angiography of aorta and successfully treated with endovascular stent-graft.
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Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes.
Synapse
PUBLISHED: 02-23-2013
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Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low-dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose-dependent inhibition of 4-AP-evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²? ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization-induced increase in [Ca²?]C but did not alter 4-AP-mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na?/Ca²? exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²?]C caused by Ca²? entry through presynaptic voltage-dependent Ca²? channels and the suppression of the PKA and PKC signaling cascades.
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Degenerate two-photon absorption and effective optical-power-limiting properties of multipolar chromophores derived from 2,3,8-trisubstituted indenoquinoxaline.
Chem Asian J
PUBLISHED: 02-20-2013
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Two analogous multipolar chromophores (1 and 2) that contained 2,3,8-trisubstituted indenoquinoxaline moieties have been synthesized and characterized for their two-photon absorption properties, both in the femtosecond and nanosecond time regimes. We demonstrated that their multi-branched framework structures, which incorporated appropriately functionalized indenoquinoxaline units, afforded large molecular nonlinear absorptivities within the studied spectroscopic range. Effective optical-power-limiting and stabilization behaviors in the nanosecond regime of dye molecule (2) were also investigated and the results indicated that such a structural motif could be a useful approach to the molecular design of highly active two-photon systems for quick-response and related broadband optical-suppressing applications, in particular for confronting laser pulses of a long duration.
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Anticoagulation education: do patients understand potential medication-related emergencies?
Jt Comm J Qual Patient Saf
PUBLISHED: 02-02-2013
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The Joint Commission Venous Thromboembolism (VTE) National Hospital Inpatient Quality Measure VTE-5 outlines four criteria for discharge patient education when starting anticoagulation (usually, warfarin) therapy. The criteria do not specify content regarding patient recognition of potentially dangerous warfarin-related scenarios. A study was conducted to investigate how well patients assess the risks and consequences of potential warfarin-related safety threats.
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Metastatic complications of pericarditis and cardiac tamponade as a result of Staphylococcus aureus bacteremia developing during antimicrobial therapy.
Intern. Med.
PUBLISHED: 02-01-2013
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Acute bacterial pericarditis is a rare but devastating complication of Staphylococcus aureus bacteremia (SAB). We herein describe the case of a previously healthy 81-year-old woman with SAB complicated by pericarditis that evolved into cardiac tamponade despite the administration of optimal antimicrobial therapy for 11 days. Three adhesion factor genes, fnbA, clfA and clfB, were identified in the causative isolate.
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Decreased SPLUNC1 expression is associated with Pseudomonas infection in surgically treated chronic rhinosinusitis patients who may require repeated sinus surgery.
Laryngoscope
PUBLISHED: 01-31-2013
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Chronic rhinosinusitis colonized with Pseudomonas aruginosa is difficult to treat and is related to biofilm formation. Repeated sinus surgery is often required for these patients. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) is an epithelium-secreted protein that is involved in innate immunity and has anti-Pseudomonas and antibiofilm functions. This study examined if SPLUNC1 expression was related to sinusitis with bacterial culture positive for Pseudomonas and the possibility of using SPLUNC1 to predict treatment outcomes for sinusitis.
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Environmental lead exposure accelerates progressive diabetic nephropathy in type II diabetic patients.
Biomed Res Int
PUBLISHED: 01-24-2013
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Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60?mL/min/1.73?m(2)) with normal body lead burden (BLB) (<600? ? g/72?hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80? ? g) and low-normal BLB (<80? ? g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100? ? g increment in BLB and each 10? ? g increment in blood lead levels could decrease GFR by 2.2?mL/min/1.72?m(2) and 3.0?mL/min/1.72?m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.
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Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-?B activation.
Osteoporos Int
PUBLISHED: 01-21-2013
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Dextromethorphan (DXM), a commonly used antitussive, is a dextrorotatory morphinan. Here, we report that DXM inhibits the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption by abrogating the activation of NF-?B signalling in vitro. Oral administration of DXM ameliorates ovariectomy (OVX)-induced osteoporosis in vivo.
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Enhancement of PLGF production by 15-(S)-HETE via PI3K-Akt, NF-?B and COX-2 pathways in rheumatoid arthritis synovial fibroblast.
Eur. J. Pharmacol.
PUBLISHED: 01-11-2013
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Metabolites from arachidonic acids play the pivotal roles in inflammatory arthritis. Arachidonic acid could be metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) to produce the bioactive eicosanoids. Although the down-stream products of COX including prostaglandin E2 are well-known inflammatory stimulators, the role of LOX products in inflammatory arthritis is still unclear. Here we found that the downstream product of 15-LOX, 15-S-hydroxyeicosatetraenoic acid (15-(S)-HETE), can enhance the expression of placenta growth factor (PLGF), which is recently considered to play an important role in rheumatoid arthritis. 15-(S)-HETE increased the expression of PLGF in human rheumatoid arthritis synovial fibroblasts in a time-dependent and concentration-dependent manner. PI3K-Akt, NF-?B signaling pathways were involved in the potentiation effects of 15-(S)-HETE. In addition, COX-2 was up-regulated by the treatment of 15-(S)-HETE and the increase of COX-2 expression participated in 15-(S)-HETE-induced PLGF expression, which was confirmed by COX-2 shRNA or pharmacological COX-2 inhibitor. Moreover, it was found that treatment of prostaglandin E2 (PGE2), which was the main down-stream metabolite of COX-2, increased the expression of PLGF. EP1, EP2, EP3 and EP4 agonists could up-regulate PLGF as well. In animal studies, we found that the adjuvant-induced expression of PLGF and COX-2 was inhibited in 15-LOX knockout mice. These results indicated that PLGF up-regulation by 15-LOX downstream product may be involved in inflammatory arthritis.
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Duplication and diversification of the spermidine/spermine N1-acetyltransferase 1 genes in zebrafish.
PLoS ONE
PUBLISHED: 01-11-2013
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Spermidine/spermine N(1)-acetyltransferase 1 (Ssat1) is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis. In addition, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis. Using cross-genomic bioinformatic analysis in 10 deuterostomes, we found that ssat1 only exists in vertebrates. Comparing with mammalian, zebrafish, an evolutionarily distant vertebrate, contains 3 homologous ssat1 genes, named ssat1a, ssat1b, and ssat1c. All zebrafish homologues could be transcribed and produce active enzymes. Despite the long history since their evolutionary diversification, some features of human SSAT1 are conserved and subfunctionalized in the zebrafish family of Ssat1 proteins. The polyamine-dependent protein synthesis was only found in Ssat1b and Ssat1c, not in Ssat1a. Further study indicated that both 5 and 3 sequences of ssat1b mediate such kind of translational regulation inside the open reading frame (ORF). The polyamine-dependent protein stabilization was only observed in Ssat1b. The last 70 residues of Ssat1b were crucial for its rapid degradation and polyamine-induced stabilization. It is worth noting that only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, were able to interact with integrin ?9 and Hif-1?. Thus, Ssat1b and Ssat1c might not only be a polyamine metabolic enzyme but also simultaneously respond to polyamine levels and engage in cross-talk with other signaling pathways. Our data revealed some correlations between the sequences and functions of the zebrafish family of Ssat1 proteins, which may provide valuable information for studies of their translational regulatory mechanism, protein stability, and physiological functions.
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Predictors of acute respiratory distress syndrome in patients with paraquat intoxication.
PLoS ONE
PUBLISHED: 01-01-2013
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Paraquat poisoning is characterized by acute lung injury, pulmonary fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate of mortality and morbidity. The objectives of this study were to identify predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat poisoning and determine the association between these parameters.
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Impact of living environment on 2-year mortality in elderly maintenance hemodialysis patients.
PLoS ONE
PUBLISHED: 01-01-2013
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Studies on risk factors of mortality in elderly patients with hemodialysis usually focus on comorbidities, nutrition, and inflammation. Discussion on the correlation between living environment and mortality of these patients is limited.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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