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Find video protocols related to scientific articles indexed in Pubmed.
Ferruginol Inhibits Non-Small Cell Lung Cancer Growth by Inducing Caspase-Associated Apoptosis.
Integr Cancer Ther
PUBLISHED: 10-31-2014
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Purpose. The anti-lung cancer effect of Cryptomeria japonica leaf extractive and its active phytocompound was evaluated using in vitro and in vivo assays. Experimental Design. The anti-lung cancer mechanism was investigated using flow cytometry and western blot analyses, and the antitumor activity was evaluated in a xenograft animal model. Results. MTT assay indicated that the cytotoxic effects of ferruginol in A549 and CL1-5 cells were dose-dependent. According to the results of cell cycle and annexin V/PI analyses, the sub-G1 population and annexin V binding in the 2 cell lines were increased after ferruginol treatment. The results of western blot analyses revealed that the cleaved forms of caspase 3, 8, 9, and poly(ADP-ribose) polymerase were activated after ferruginol treatment in A549 and CL1-5 cells. Moreover, the expression of the anti-apoptotic protein Bcl-2 was decreased, while the expression of the pro-apoptotic protein Bax was elevated, after ferruginol treatment in both lung cancer cell lines. These results indicated that ferruginol acted via a caspase-dependent mitochondrial apoptotic pathway in the 2 cell lines. Intraperitoneal administration of ferruginol significantly suppressed the growth of subcutaneous CL1-5 xenografts. Conclusions. The findings of the present study provided insight into the molecular mechanisms underlying ferruginol-induced apoptosis in non-small cell lung cancer (NSCLC) cells, indicating that this compound may be a potential candidate drug for anti-NSCLC.
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Inhibition of RAC1 GTPase sensitizes pancreatic cancer cells to g-irradiation.
Oncotarget
PUBLISHED: 10-27-2014
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Radiation therapy is a staple treatment for pancreatic cancer. However, owing to the intrinsic radioresistance of pancreatic cancer cells, radiation therapy often fails to increase survival of pancreatic cancer patients. Radiation impedes cancer cells by inducing DNA damage, which can activate cell cycle checkpoints. Normal cells possess both a G1 and G2 checkpoint. However, cancer cells are often defective in G1 checkpoint due to mutations/alterations in key regulators of this checkpoint. Accordingly, our results show that normal pancreatic ductal cells respond to ionizing radiation (IR) with activation of both checkpoints whereas pancreatic cancer cells respond to IR with G2/M arrest only. Overexpression/hyperactivation of Rac1 GTPase is detected in the majority of pancreatic cancers. Rac1 plays important roles in survival and Ras-mediated transformation. Here, we show that Rac1 also plays a critical role in the response of pancreatic cancer cells to IR. Inhibition of Rac1 using specific inhibitor and dominant negative Rac1 mutant not only abrogates IR-induced G2 checkpoint activation, but also increases radiosensitivity of pancreatic cancer cells through induction of apoptosis. These results implicate Rac1 signaling in the survival of pancreatic cancer cells following IR, raising the possibility that this pathway contributes to the intrinsic radioresistance of pancreatic cancer.
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Reduced-intensity FOLFOXIRI in Treating Refractory Metastatic Colorectal Cancer: A Pilot Study.
Am. J. Clin. Oncol.
PUBLISHED: 10-22-2014
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To report on the efficacy and safety of reduced-intensity FOLFOXIRI (RI-FOLFOXIRI) as salvage chemotherapy for patients with refractory metastatic colorectal cancer (mCRC).
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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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Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.
Acta Neuropathol Commun
PUBLISHED: 10-15-2014
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Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.
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Accumulated Mental Stress Study Using the Meridians of Traditional Chinese Medicine with Photoplethysmography.
J Altern Complement Med
PUBLISHED: 10-15-2014
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Abstract Objectives: To investigate accumulated mental stress according to the concept of the meridians of Traditional Chinese Medicine (TCM). This stress was quantified by using pulse spectrum analysis of finger-tip photoplethysmography (PPG). Stress accumulation is one of the main causes of cardiovascular disease and depression in humans, resulting in chronic physiologic malfunctions; however, few studies have thoroughly assessed the quantitative evaluation of accumulative stress using the concept of TCM. Design: This study investigated accumulated mental stress from the perspective of TCM based on an 8-day experiment. The theory of organ resonance was integrated into the proposed PPG sensing instrument to capture the nine harmonics of TCM. Participants were given daily mental arithmetic tasks over 1 week to simulate stress accumulation, and trends in the proportion of the nine harmonics of TCM were extracted over several days and analyzed to identify the affective factors related to cumulative stress. Results: The experimental results showed that the kidney harmonic proportion (C2) and stomach harmonic proportion (C5) were significant only on the first few days because of a physiologic phenomenon of temporary stimulation. Most important, the trend of the liver harmonic proportion (C1) from days 3 to 8 dramatically increased and became gradually saturated because of the influence of accumulated mental stress. Conclusions: The results strongly suggest that pulse spectrum analysis of the PPG signal provides physiologically and pathologically important information on accumulated mental stress and can be useful for TCM analysis.
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Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-09-2014
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Interferon-gamma (IFN-?) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-? are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-? on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-? treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-? increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-?-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-?. These results provide new mechanistic insights into interferon-? antitumor activity and further support IFN-? as a potential therapeutic adjuvant for the treatment of NCSLC.
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Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum.
Brain
PUBLISHED: 10-01-2014
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Structural changes in Purkinje cells have been identified in the essential tremor cerebellum, although the mechanisms that underlie these changes remain poorly understood. Climbing fibres provide one of the major excitatory inputs to Purkinje cells, and climbing fibre-Purkinje cell connections are essential for normal cerebellar-mediated motor control. The distribution of climbing fibre-Purkinje cell synapses on Purkinje cell dendrites is dynamically regulated and may be altered in disease states. The aim of the present study was to examine the density and distribution of climbing fibre-Purkinje cell synapses using post-mortem cerebellar tissue of essential tremor cases and controls. Using vesicular glutamate transporter type 2 immunohistochemistry, we labelled climbing fibre-Purkinje cell synapses of 12 essential tremor cases and 13 age-matched controls from the New York Brain Bank. Normally, climbing fibres form synapses mainly on the thick, proximal Purkinje cell dendrites in the inner portion of the molecular layer, whereas parallel fibres form synapses on the thin, distal Purkinje cell spiny branchlets. We observed that, compared with controls, essential tremor cases had decreased climbing fibre-Purkinje cell synaptic density, more climbing fibres extending to the outer portion of the molecular layer, and more climbing fibre-Purkinje cell synapses on the thin Purkinje cell spiny branchlets. Interestingly, in essential tremor, the increased distribution of climbing fibre-Purkinje cell synapses on the thin Purkinje cell branchlets was inversely associated with clinical tremor severity, indicating a close relationship between the altered distribution of climbing fibre-Purkinje cell connections and tremor. These findings suggest that abnormal climbing fibre-Purkinje cell connections could be of importance in the pathogenesis of essential tremor.
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Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells.
Mol Biosyst
PUBLISHED: 09-27-2014
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Rhein is a natural product purified from herbal plants such as Rheum palmatum, which has been shown to have anti-angiogenesis and anti-tumor metastasis properties. However, the biological effects of rhein on the behavior of breast cancers are not completely elucidated. To evaluate whether rhein might be useful in the treatment of breast cancer and its cytotoxic mechanism, we analyzed the impact of rhein treatment on differential protein expression as well as redox regulation in a non-invasive breast cancer cell line, MCF-7, and an invasive breast cancer cell line, MDA-MB-231, using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry. This proteomic study revealed that 73 proteins were significantly changed in protein expression; while 9 proteins were significantly altered in thiol reactivity in both MCF-7 and MDA-MB-231 cells. The results also demonstrated that rhein-induced cytotoxicity in breast cancer cells mostly involves dysregulation of cytoskeleton regulation, protein folding, the glycolysis pathway and transcription control. A further study also indicated that rhein promotes misfolding of cellular proteins as well as unbalancing of the cellular redox status leading to ER-stress. Our work shows that the current proteomic strategy offers a high-through-put platform to study the molecular mechanisms of rhein-induced cytotoxicity in breast cancer cells. The identified differentially expressed proteins might be further evaluated as potential targets in breast cancer therapy.
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Novel triarylamine-based polybenzoxazines with a donor-acceptor system for polymeric memory devices.
Chem. Commun. (Camb.)
PUBLISHED: 09-26-2014
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Novel polybenzoxazines consisting of electron-donating triphenylamine derivatives and electron-withdrawing 4,4'-diphenyl sulfone moieties were successfully prepared by the thermally induced ring-opening reaction of the corresponding PB precursors and utilized for memory devices.
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Spatial and Temporal Analysis on the Distribution of Active Radio-Frequency Identification (RFID) Tracking Accuracy with the Kriging Method.
Sensors (Basel)
PUBLISHED: 09-13-2014
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Radio frequency identification (RFID) technology has already been applied in a number of areas to facilitate the tracking process. However, the insufficient tracking accuracy of RFID is one of the problems that impedes its wider application. Previous studies focus on examining the accuracy of discrete points RFID, thereby leaving the tracking accuracy of the areas between the observed points unpredictable. In this study, spatial and temporal analysis is applied to interpolate the continuous distribution of RFID tracking accuracy based on the Kriging method. An implementation trial has been conducted in the loading and docking area in front of a warehouse to validate this approach. The results show that the weak signal area can be easily identified by the approach developed in the study. The optimum distance between two RFID readers and the effect of the sudden removal of readers are also presented by analysing the spatial and temporal variation of RFID tracking accuracy. This study reveals the correlation between the testing time and the stability of RFID tracking accuracy. Experimental results show that the proposed approach can be used to assist the RFID system setup process to increase tracking accuracy.
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Undifferentiated Wharton?s Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T Cell-Mediated Autoimmunity in Non-Obese Diabetic Mice.
Cell Transplant
PUBLISHED: 09-09-2014
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Type 1 diabetes mellitus (T1DM) is caused by T cell-mediated autoimmune destruction of pancreatic ?cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We previously showed that human MSCs isolated from Wharton?s Jelly (WJ-MSCs) represent a potential cell source to treat diabetes. However, the underlying mechanisms are unclear. The purpose of this study was to discern whether undifferentiated WJ-MSCs can differentiate into pancreatic insulin-producing cells (IPCs) and modify immunological responses in non-obese diabetic (NOD) mice. Undifferentiated WJ-MSCs underwent lentiviral transduction to express green fluorescent protein (GFP) and then were injected into the retro-orbital venous sinus of NOD mice. Seven days after transplantation, fluorescent islet-like cell clusters in the pancreas were apparent. WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T cells, including T helper 1 cells and IL-17-producing T cells, were reduced and regulatory T cell levels were increased. Furthermore, anti-inflammatory cytokine levels were increased and dendritic cells were decreased. At 23 days, higher human C-peptide and serum insulin levels and improved glucose tolerance were found. Additionally, WJ-MSCs-GFP differentiated into IPCs as shown by colocalization of human C-peptide and GFPin the pancreas. Significantly more intact islets and less severe insulitis were observed. In conclusion, undifferentiated WJ-MSCs candifferentiate into insulin-producing cells in vivo with immunomodulatory effects and repair the destroyed islets in NOD mice.
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Sleep Apnea and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.
Sleep
PUBLISHED: 08-06-2014
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Sleep apnea (SA) is characterized by apnea during sleep and is associated with cardiovascular diseases and an increase in all-cause mortality. Chronic kidney disease (CKD) is a global health problem that has placed a substantial burden on healthcare resources. However, the relationship between SA and the incidence of CKD is not clear. This study aimed to determine whether SA is an independent risk factor for the development of CKD.
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A comparison of inpatients with anxious depression to those with nonanxious depression.
Psychiatry Res
PUBLISHED: 07-17-2014
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Anxiety symptoms are common for patients with major depressive disorder (MDD). Anxious depression has been considered MDD with high levels of anxiety symptoms. The objective of this study was to investigate the factors associated with anxious depression for Chinese inpatients with MDD. A total of 174 acutely ill patients were enrolled. Baseline demographic variables, suicide risk, depression severity, quality of life (QOL), and daily functional impairment were assessed. Those MDD patients with a 17-item Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor score?7 were defined as anxious depression. Logistic regression was employed to examine the factors associated with anxious depression. One hundred and forty-one (81.0%) of the subjects reported anxious depression. Patients with anxious depression were more likely to have melancholic features, to be older, to experience more severe depression, to be at greater risk of suicide, to have more pain, poorer quality of life, and more severe functional impairment. Anxious depression is common in inpatients with MDD. These findings suggest that anxious depression significantly differs from nonanxious depression on several clinically relevant variables. These data add to a growing body of evidence that anxious depression is a more complex presentation of depression.
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Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: Reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.
Pharmacol. Res.
PUBLISHED: 07-09-2014
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Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2?M cells and MES-SA/DxR-8?M cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.
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Cotton-based Diagnostic Devices.
Sci Rep
PUBLISHED: 06-30-2014
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A good diagnostic procedure avoids wasting medical resources, is easy to use, resists contamination, and provides accurate information quickly to allow for rapid follow-up therapies. We developed a novel diagnostic procedure using a "cotton-based diagnostic device" capable of real-time detection, i.e., in vitro diagnostics (IVD), which avoids reagent contamination problems common to existing biomedical devices and achieves the abovementioned goals of economy, efficiency, ease of use, and speed. Our research reinforces the advantages of an easy-to-use, highly accurate diagnostic device created from an inexpensive and readily available U.S. FDA-approved material (i.e., cotton as flow channel and chromatography paper as reaction zone) that adopts a standard calibration curve method in a buffer system (i.e., nitrite, BSA, urobilinogen and uric acid assays) to accurately obtain semi-quantitative information and limit the cross-contamination common to multiple-use tools. Our system, which specifically targets urinalysis diagnostics and employs a multiple biomarker approach, requires no electricity, no professional training, and is exceptionally portable for use in remote or home settings. This could be particularly useful in less industrialized areas.
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The role of adjuvant chemotherapy in stage II colorectal cancer patients.
Int J Colorectal Dis
PUBLISHED: 06-22-2014
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Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response.
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[Remarks on the relationship between deqi and effect of acupuncture].
Zhongguo Zhen Jiu
PUBLISHED: 06-21-2014
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Acupuncturists have always paid high attention to deqi (needling sensation) in clinical. However, relationship between deqi and curative effect has not been elucidated yet. In order to have a further understanding on effect of deqi on clinical effect, through study on literature associated with deqi since the establishment of People's Republic of China in 1949, it is held that various factors can influence therapeutic effect of acupuncture treatment, including whether needling sensation appears or not, the speed of deqi, the intensity of deqi, different types of sensations as well as propagated sensation along meridians (PSM). Joint launched multidisciplinary researches should be carried out to reveal the influence principle of deqi on acupuncture effect, and to lay foundations for the further studies on mechanism of deqi.
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Tazarotene induces apoptosis in human basal cell carcinoma via activation of caspase-8/t-Bid and the reactive oxygen species-dependent mitochondrial pathway.
DNA Cell Biol.
PUBLISHED: 06-13-2014
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Previous studies suggest that tazarotene, a new member of the acetylenic class of RAR?/? selective retinoids which is approved to treat a variety of skin diseases, exhibits an anti-proliferative effect in human basal cell carcinoma (BCC) by triggering caspase-dependent apoptosis. However, the detailed molecular mechanisms underlying the anti-tumor activity of tazarotene are poorly understood. This study aims at investigating the molecular mechanisms of tazarotene-induced apoptosis in human BCC cells. Our results are the first to demonstrate that tazarotene induces mitochondria-dependent cleavage of caspase-9 and -3 and PARP in BCC cells by producing reactive oxygen species (ROS) and activating caspase-8 through both ROS and death receptor signaling. These events are accompanied by a decrease in BCL-2 and BCL-xl anti-apoptotic proteins as well as by survivin and XIAP, two IAP family members. Furthermore, our results presented for the first time that tazarotene triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the caspase-8-truncated Bid signaling pathway. Collectively, these data provide insights into the molecular mechanisms underlying tazarotene-induced apoptosis in human BCC cells, suggesting that this compound is a potential anti-skin cancer drug.
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Explicit and implicit heroin-related cognitions and heroin use among patients receiving methadone maintenance treatment.
Compr Psychiatry
PUBLISHED: 06-03-2014
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Craving is an important issue in substance use disorder. To achieve a better understanding of the cognitive processing systems of craving, the cognitive processes of craving have been considered as two distinct processes. One system, based on rule-based inferences and named explicit cognition, is more conscious and effortful. The other system, based on prior learned association and named implicit cognition, is unconscious and effortless. How explicit and implicit cognitions are associated with heroin use in patients with methadone maintenance treatment (MMT) is not clear. This study aimed to explore the relationship between explicit and implicit cognition and heroin use in patients undergoing MMT.
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Increased risk of hip fractures in patients with dementia: a nationwide population-based study.
BMC Neurol
PUBLISHED: 05-26-2014
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BackgroundDementia has been associated with an increased risk of hip fracture. However, little research has been conducted on the impact of dementia on wrist or vertebral fracture development. The aim of this study was to investigate whether dementia is a risk factor for different types of fracture in Taiwan.MethodsThe study sample was drawn from Taiwan¿s National Health Insurance Research Database of reimbursement claims, and comprised 1408 patients who visited ambulatory care centers or were hospitalized with a diagnosis of dementia. The comparison group consisted of 7040 randomly selected individuals. Cox proportional hazard regression model was used to examine associations between dementia and the risk of different types of fracture.ResultsDuring a 3-year follow-up period, 264 patients with dementia (18.75%) and 1098 patients without dementia (15.60%) developed fractures. Dementia was independently associated with increased risk of hip fracture [adjusted hazard ratio (HR) 1.92, 95% CI 1.48¿2.49]. Patients with dementia and osteoporosis had the highest risk of developing hip fracture (adjusted HR 2.27, 95% CI 1.28¿4.01). Dementia did not increase wrist fracture or vertebral fracture risk when compared to the control group, even in patients with osteoporosis.ConclusionsIndividuals with dementia are at greater risk of developing hip fracture, particularly if they also have osteoporosis. Early mental screening programs and health education should be initiated to decrease disability and dependence in patients with dementia.
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Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors.
Carcinogenesis
PUBLISHED: 05-15-2014
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Embryonal tumors of the central nervous system represent a highly malignant tumor group of medulloblastoma (MB), atypical teratoid/rhabdoid tumor (AT/RT) and primitive neuroectodermal tumor that frequently afflict children. AT/RT is often misdiagnosed as MB/primitive neuroectodermal tumor but with higher recurrence and lower survival rates. Pathogenesis of AT/RT is largely unknown. In this study, we report both the miRNome and transcriptome traits in AT/RT and MB by using small RNA sequencing and gene expression microarray analyses. Our findings demonstrate that the miR-221/222-encoded micro RNAs are abundantly expressed in AT/RT but not in MB, which contribute substantially to the malignancy of embryonal tumors. miR-221/222 targeted SUN2, a newly discovered tumor suppressor, directly to increase cell proliferation and tumor malignancy in vitro and in vivo. Immunohistochemistry against SUN2 in a tissue microarray of 33 AT/RT and 154 MB tumor specimens also detected less SUN2 protein in AT/RT. Collectively, this study uncovers a novel tumor suppressor, SUN2, plays a critical role in miR-221/222-mediated AT/RT malignancy as well as supports miR-221/222 and SUN2 represent new promising targets for more active therapies in AT/RT. In addition, our miRNome and transcriptome data also provide a roadmap for further embryonal tumor research.
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Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes.
J Ethnopharmacol
PUBLISHED: 05-06-2014
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Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have investigated the comparative pharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment.
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Anti-cancer effects of ursane triterpenoid as a single agent and in combination with cisplatin in bladder cancer.
Eur. J. Pharmacol.
PUBLISHED: 05-01-2014
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Ursolic acid and most of its derivatives are cytotoxic to bladder cancer cells. An ursolic acid derivative, isopropyl 3?-hydroxyurs-12-en-28-oat (UA17), previously reported that it exhibited potent cytotoxicity against bladder cancer cells, NTUB1 cells. In this study, we further investigated the underlying mechanism of UA17 and evaluated its potential clinical use. UA17 may exert the onset of a p53-mediated p38 MAPK activation to up-regulate GADD153. GADD153, in turn, down-regulated Bcl-2 protein to cause mitochondrial membrane potential loss and apoptosis through intracellular ROS generation. In addition, UA17 markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (CDK2 and CDK4), and caused increase of p21 and p27 levels. To assess the suitability of UA17 as a chemotherapeutic agent against NTUB1 cells, its cytotoxic effects have been further evaluated in the combination with cisplatin. The addition of UA17 to cisplatin induces possibly additive cell growth inhibition which correlated to the accumulation of S phase cells and a corresponding decrease in accumulation of G1 phase cells, accompanied an increased accumulation of sub-G1 phase cells. Furthermore, UA17/cisplatin combination exhibited increase of p21, cyclin E, and p-p53 level, and decrease of p27 and cyclin D1 proteins, and slightly diminishing the level of CDK2. P-p38 up-regulation induced by UA17/cisplatin combination through generation of ROS and Bcl-2 down-regulation induced by UA17/cisplatin combination increased cell death. Finally, the antitumorigenic effects of UA17 or UA17/cisplatin combination were further supported by their inhibition on growth of bladder tumor cells in a therapeutic murine MBT-2 bladder tumor model.
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Transcription factor Snail regulates TNF-?-mediated synovial fibroblast activation in rheumatoid joint.
PUBLISHED: 04-10-2014
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Objective. Transcription factor Snail is involved in various biological functions. We hypothesized that this molecule regulates TNF-?-mediated synovial fibroblasts (SF) activation in rheumatoid joint, and examined its roles in expression of Cadherin-11 (Cad-11) and myofibroblast markers, invasive ability and IL-6 production. Methods. Synovium was obtained from rheumatoid arthritis (RA) patients and collagen-induced arthritis (CIA) rats. SF were treated with TNF-? or a Wnt signaling inducer, and CIA joints were injected with a TNF-? antagonist. Modulation of Snail expression in SF and joints was performed by lentiviral vector-mediated transfer of cDNA or short hairpin RNA. Results. Snail and Cad-11 were expressed at higher levels in synovium and SF from RA patients and CIA rats. TNF-? stimulation or Wnt signaling activation upregulated the expression levels of Snail, Cad-11 and ?-smooth muscle actin (SMA) in SF, and anti-TNF-? therapy down-regulated their expression levels in CIA joints. While Snail-overexpressed SF transfectants had increased expression levels of Cad-11 and ?-SMA and enhanced TNF-?-mediated invasive capacity and IL-6 production, Snail-knockdowned CIASF transfectants had decreased expression levels and the opposite effect on these functions. Snail-overexpressed normal joints had hyperplastic synovium with increased expression levels of Cad-11, ?-SMA and IL-6. Silencing Snail expression ameliorated arthritis with reduced Cad-11 expression and extracellular matrix deposition levels in CIA joints, whereas overexpression of Snail exacerbated arthritis with increased expression and deposition levels. Conclusion. Our results demonstrate that Snail regulates TNF-?-mediated SF activation in rheumatoid joint, and these findings might contribute to the pharmacological development of therapeutics targeting SF in RA patients. © 2014 American College of Rheumatology.
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The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer.
J Surg Oncol
PUBLISHED: 04-07-2014
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This study aimed to establish a correlation between MSI, KRAS mutations, and BRAF(V600E) in colon cancer and to investigate the prognostic effect.
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Interleukin-17A modulates circulating tumor cells in tumor draining vein of colorectal cancers and affects metastases.
Clin. Cancer Res.
PUBLISHED: 03-27-2014
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Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC.
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Immunomodulation of phloretin by impairing dendritic cell activation and function.
Food Funct
PUBLISHED: 03-22-2014
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Dietary compounds in fruits and vegetables have been shown to exert many biological activities. In addition to antioxidant effects, a number of flavonoids are able to modulate inflammatory responses. Here, we demonstrated that phloretin (PT), a natural dihydrochalcone found in many fruits, suppressed the activation and function of mouse dendritic cells (DCs). Phloretin disturbed the multiple intracellular signaling pathways in DCs induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), including ROS, MAPKs (ERK, JNK, p38 MAPK), and NF-?B, and thereby reducing the production of inflammatory cytokines and chemokines. Phloretin also effectively suppressed the activation of DCs treated with different dosages of LPS or various TLR agonists. The LPS-induced DC maturation was attenuated by phloretin because the expression levels of the MHC class II and the co-stimulatory molecules were down-regulated, which then inhibited the LPS-stimulating DCs and the subsequent naïve T cell activation in a mixed lymphocyte reaction. Moreover, in vivo administration of phloretin suppressed the phenotypic maturation of the LPS-challenged splenic DCs and decreased the IFN-? production from the activated CD4 T cells. Thus, we suggest that phloretin may potentially be an immunomodulator by impairing the activation and function of DCs and phloretin-contained fruits may be helpful in the improvement of inflammation and autoimmune diseases.
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Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for patients with metastatic colorectal cancer: Superior progression-free survival is restricted to patients with measurable tumors and objective tumor response-a retrospective study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-18-2014
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We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.
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NBT-II cell locomotion is modulated by restricting the size of focal contacts and is improved through EGF and ROCK signaling.
Int. J. Biochem. Cell Biol.
PUBLISHED: 03-14-2014
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Focal contacts, large macromolecular complexes that link the extracellular matrix and the internal cell cytoskeleton, are thought to govern cell locomotion. However, the maturation process through which focal contacts control the cellular migratory machinery by changes in size and molecular composition remain unclear. Here, we fabricated cell growth substrates that contained linear ECM strips of micron- or submicron-width in order to limit the enlargement of focal contacts. We found that NBT-II cells plated on the submicron substrate possessed smaller focal complexes that exhibited a highly dynamic turnover. These cells possessed various leading edges at multiple sites of the cell periphery, which prevented the cell from advancing. In contrast, cells grown on the micron-width substrate possessed large and stable focal adhesions. Most of these cells were elongated bipolar cells that were tethered at both ends and were immobile. Further, EGF and ROCK signaling pathways can modulate the cellular migratory responses according to the substrate guidance. On the submicron-width substrate, EGF treatment increased the focal contact size and the contractile force, causing these cells to develop one leading edge and migrate along the submicron-sized ECM paths. In contrast, inhibition of ROCK signaling decreased the focal contact size for cells plated on the micron substrate. These cells became less tethered and were able to migrate along or even across the micron-sized ECM paths. Our results indicate that formation and maturation of focal contacts is controlled by both ECM cues and intracellular signaling and they play a central role in directed cell motion.
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A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction.
J. Cell. Mol. Med.
PUBLISHED: 03-10-2014
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Toll-like receptors (TLR) recognize pathogens and trigger the production of vigorous pro-inflammatory cytokines [such as tumour necrosis factor (TNF)] that induce systemic damages associated with sepsis and chronic inflammation. Cooperation between signals of TLR and TNF receptor has been demonstrated through the participation of TNF receptor 1 (TNFR) adaptors in endotoxin tolerance. Here, we identify a TLR2-mediated synergy, through a MyD88-independent crosstalk, which enhances subsequent TNF-mediated nuclear factor-kappa B activation and interleukin-6 induction. Membrane-associated adaptor MAL conduces the link between TNF receptor-associated factor 6 (TRAF6) and TNFR-associated death domain, leading to a distinctive K63-ubiquitinylated TRAF6 recruitment into TNFR complex. In summary, our results reveal a novel route of TLR signal that synergistically amplifies TNF-mediated responses, indicating an innovative target for inflammation manipulation.
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Promoting positive psychology using social networking sites: a study of new college entrants on Facebook.
Int J Environ Res Public Health
PUBLISHED: 02-28-2014
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This study explores the potential of promoting college students' positive psychological development using popular online social networks. Online social networks have dramatically changed the ways college students manage their social relationships. Social network activities, such as checking Facebook posts dominates students' Internet time and has the potential to assist students' positive development. Positive psychology is a scientific study of how ordinary individuals can apply their strength effectively when facing objective difficulties and how this capability can be cultivated with certain approaches. A positive message delivery approach was designed for a group of new college entrants. A series of positive messages was edited by university counselors and delivered by students to their Facebook social groups. Responses from each posted positive messages were collected and analyzed by researchers. The responses indicated that: (1) relationships of individual engagement and social influence in this study can partially explain the observed student behavior; (2) using class-based social groups can promote a positive atmosphere to enhance strong-tie relationships in both the physical and virtual environments, and (3) promoting student's positive attitudes can substantially impact adolescents' future developments, and many positive attitudes can be cultivated by emotional events and social influence.
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Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition.
Oncotarget
PUBLISHED: 02-26-2014
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Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified as a potential target in osteosarcoma (OS). 15-deoxy-?12, 14-prostaglandin J2 (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of v-akt, a murine thymoma viral oncogene homolog, (AKT) in cancer cells. In the study analyzing its effects on arthritis, 15d-PGJ2 mediated shear-induced chondrocyte apoptosis via protein kinase A (PKA)-dependent regulation of PLK1. In this study, the cytotoxic effect and mechanism underlying 15d-PGJ2 effects against OS were explored using OS cell lines. 15d-PGJ2 induced significant G2/M arrest, and exerted time- and dose-dependent cytotoxic effects against all OS cell lines. Western blot analysis showed that both AKT and PKA-PLK1 were down-regulated in OS cell lines after treatment with 15d-PGJ2. In addition, transfection of constitutively active AKT or PLK1 partially rescued cells from 15d-PGJ2-induced apoptosis, suggesting crucial roles for both pathways in the anti-cancer effects of 15d-PGJ2. Moreover, ROS generation was found treatment with 15d-PGJ2, and its cytotoxic effect could be reversed with N-acetyl-l-cysteine. Furthermore, inhibition of JNK partially rescued 15d-PGJ2 cytotoxicity. Thus, ROS-mediated JNK activation may contribute to apoptosis through down-regulation of the p-Akt and PKA-PLK1 pathways. 15d-PGJ2 is a potential therapeutic agent for OS, exerting cytotoxicity mediated through both AKT and PKA-PLK1 inhibition, and these results form the basis for further analysis of its role in animal studies and clinical applications.
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Antihelminthic niclosamide modulates dendritic cells activation and function.
Cell. Immunol.
PUBLISHED: 02-25-2014
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Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-? production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-?B may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases.
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Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS/MS.
Molecules
PUBLISHED: 02-17-2014
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Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the comparative pharmacokinetics of rhein in rats. A sensitive and specific method combining liquid chromatography with electrospray ionization tandem mass spectrometry has been developed and validated to simultaneously quantify six active compounds in the pharmaceutical herbal product SHXXT to further study their pharmacokinetics in rats. Multiple reaction monitoring (MRM) was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. There were no significant matrix effects in the quantitative analysis and the mean recovery for rhein in rat plasma was 91.6%±3.4%. The pharmacokinetic data of rhein demonstrate that the herbal formulae or the single herbal extract provide significantly higher absorption rate than the pure compound. This phenomenon suggests that the other herbal ingredients of SHXXT and rhubarb extract significantly enhance the absorption of rhein in rats. In conclusion, the herbal formulae (SHXXT) are more efficient than the single herb (rhubarb) or the pure compound (rhein) in rhein absorption.
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C5L2 is required for C5a-triggered receptor internalization and ERK signaling.
Cell. Signal.
PUBLISHED: 02-12-2014
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C5L2 is a receptor that binds to C5a and belongs to the family of G protein-coupled receptors, but its role in physiological C5a-mediated responses remains under debate. Here we show that, like the canonical C5a receptor C5aR, C5L2 plays a pro-inflammatory role in a murine model of acute experimental colitis. We demonstrate that C5L2 physically interacts with C5aR and is required for optimal C5a-mediated C5aR internalization and associated ERK activation. Abrogation of C5a-induced receptor internalization by treatment with the dynamin inhibitor dynasore(TM) impaired C5a-induced MEK and ERK signaling. Although the presence of C5aR alone was sufficient to recruit the scaffold protein ?-arrestin1 to the cell membrane in response to C5a stimulation, it was inadequate to mediate AP2 recruitment and subsequent C5aR internalization. Expression of C5L2 allowed normal internalization of C5aR in response to C5a stimulation, followed by normal ERK signaling. Thus, our work reveals an essential role for C5L2 in C5a-triggered, AP2-dependent C5aR internalization and downstream ERK signaling.
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Association between school bullying levels/types and mental health problems among Taiwanese adolescents.
Compr Psychiatry
PUBLISHED: 02-11-2014
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Few studies have compared the risks of mental health problems among the adolescents with different levels and different types of bullying involvement experiences.
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Formulated extract from multiple citrus peels impairs dendritic cell functions and attenuates allergic contact hypersensitivity.
Int. Immunopharmacol.
PUBLISHED: 02-05-2014
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It has been reported that gold lotion (GL), a formulated product made from the peels of six citrus fruits, has many pharmacological properties, such as anti-tumor, antioxidant, and anti-inflammatory activities. In this study, we investigated the immunomodulatory effect of GL on lipopolysaccharide (LPS) stimulated mouse bone marrow-derived DC maturation and function. Our experimental results have shown that GL significantly impaired the pro-inflammatory cytokine and chemokine secretion, suppressed the expression of major histocompatibility complex class I/II and costimulatory molecules (CD40, CD80 and CD86), increased phagocytic capacity, and reduced propensity to stimulate the autologous CD4(+) and CD8(+) T cell proliferation of LPS-induced DCs. Furthermore, we found that oral administration of GL attenuated the 2,4-Dinitro-1-fluorobenzene induced contact hypersensitivity (CHS) in animal models. Subsequently, our molecular mechanism studies showed that GL interfered with LPS-induced MAPK-JNK, p38 phosphorylation and nuclear translocation of NF-?B p65. In an essence, these findings are the first report to provide new insight in the immunopharmacological role of GL in terms of its effects on DC.
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Newly diagnosed dementia and increased risk of hemorrhagic stroke: A nationwide population-based study.
Curr Alzheimer Res
PUBLISHED: 02-04-2014
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This retrospective cohort study was designed to assess whether there is an association between newly diagnosed dementia and the risk of stroke.
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Hospital-based school for children with chronic illness in Taiwan.
J. Formos. Med. Assoc.
PUBLISHED: 01-28-2014
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To provide educational support and avoid unwanted damage that may impede learning for children with chronic illness, the learning environment should be friendly and safe. There is a need to establish schools inside hospitals, however, which may be neglected in a highly efficient health care system. A study was conducted to identify hospital-based schools for sick children in Taiwan, and to explore the barriers for implementation.
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The association between suicidality and Internet addiction and activities in Taiwanese adolescents.
Compr Psychiatry
PUBLISHED: 01-25-2014
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The aims of this cross-sectional study were to examine the associations of suicidal ideation and attempt with Internet addiction and Internet activities in a large representative Taiwanese adolescent population.
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Genetic variations in Toll-like receptors (TLRs 3/7/8) are associated with systemic lupus erythematosus in a Taiwanese population.
Sci Rep
PUBLISHED: 01-22-2014
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Toll-like receptors (TLRs), as innate immunity sensors, play critical roles in immune responses. Six SNPs of TLR3, TLR7, and TLR8 were genotyped to determine their associations with systemic lupus erythematosus (SLE) and clinical manifestations of SLE. TLR7 SNP rs3853839 was independently associated with SLE susceptibility in females (G vs. C: p = 0.0051). TLR7 rs3853839-G (G vs. C: p = 0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p = 0.0161) were associated with pericardial effusion in females relative to healthy females. Anti-SSA positive cases were more likely to have the dominant TLR7 rs179010-T allele than normal controls (p = 0.0435). TLR3 rs3775296-T was associated with photosensitivity (p = 0.0020) and anemia (p = 0.0082). The "G-G" haplotype of TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females (age adjusted p = 0.0032). These findings suggest that TLR variations that modify gene expression affect risk for SLE susceptibility, clinical phenotype development, and production of autoantibodies.
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Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-20-2014
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A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer.
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Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer.
Am. J. Surg.
PUBLISHED: 01-16-2014
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Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT).
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Genetic variations are associated with lymph node metastasis in colorectal cancer patients.
J Surg Oncol
PUBLISHED: 01-15-2014
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Regional lymph nodes (LNs) are believed to be a first-line barrier against tumor metastasis. However, it remains unclear whether underlying genetic factors exist and affect LN metastasis risk. We therefore evaluated inherited risk variants using single nucleotide polymorphisms (SNPs) in pathological T3 colorectal cancer patients in the absence or presence of LN metastasis.
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The effects of gout on left atrial volume remodelling: a prospective echocardiographic study.
Rheumatology (Oxford)
PUBLISHED: 01-09-2014
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The aim of the present study was to investigate the effect of gout on left ventricular (LV) diastolic function and left atrial volume (LAV).
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Association of FCGR3A and FCGR3B Copy Number Variations With Systemic Lupus Erythematosus and Rheumatoid Arthritis in Taiwanese Patients.
PUBLISHED: 01-06-2014
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To determine whether copy number variations (CNVs) in FCGR3A and FCGR3B are associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese individuals.
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Development of a microarray for two rice subspecies: characterization and validation of gene expression in rice tissues.
BMC Res Notes
PUBLISHED: 01-03-2014
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Rice is one of the major crop species in the world helping to sustain approximately half of the global population's diet especially in Asia. However, due to the impact of extreme climate change and global warming, rice crop production and yields may be adversely affected resulting in a world food crisis. Researchers have been keen to understand the effects of drought, temperature and other environmental stress factors on rice plant growth and development. Gene expression microarray technology represents a key strategy for the identification of genes and their associated expression patterns in response to stress. Here, we report on the development of the rice OneArray® microarray platform which is suitable for two major rice subspecies, japonica and indica.
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More safer sex intervention needed for HIV-positive MSM with higher education level for prevention of sexually transmitted hepatitis C.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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The epidemiology of hepatitis C virus (HCV) infections in Chinese HIV-infected men who have sex with men (MSM) remains obscure. More data is required to understand the epidemic and set up preventive strategy.
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Evaluation of serum anti-mullerian hormone as a biomarker of early ovarian aging in young women undergoing IVF/ICSI cycle.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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To determine whether or not the level of serum anti-Müllerian hormone (AMH) is related to early ovarian aging in young women (< 35 years of age) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles.
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Enhanced sensitivity of surface plasmon resonance phase-interrogation biosensor by using oblique deposited silver nanorods.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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Sensitivity of surface plasmon resonance phase-interrogation biosensor is demonstrated to be enhanced by oblique deposited silver nanorods. Silver nanorods are thermally deposited on silver nanothin film by oblique angle deposition (OAD). The length of the nanorods can be tuned by controlling the deposition parameters of thermal deposition. By measuring the phase difference between the p and s waves of surface plasmon resonance heterodyne interferometer with different wavelength of incident light, we have demonstrated that maximum sensitivity of glucose detection down to 7.1?×?10(-8) refractive index units could be achieved with optimal deposition parameters of silver nanorods.
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Impact of gout on left atrial function: a prospective speckle-tracking echocardiographic study.
PLoS ONE
PUBLISHED: 01-01-2014
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The purpose of our study was to evaluate the left ventricular (LV) and left atrial (LA) function in patients with gout. A total of 173 patients underwent a comprehensive Doppler-echocardiography examination. Participants were divided into four groups-Stage 0: control (n = 35), Stage I: asymptomatic hyperuricemia (n = 30), Stage II: gouty arthritis without tophi (n = 58), and Stage III: tophaceous gout (n = 50). Serum uric acid levels were not significantly different between stage I, II and III. Stage III patients demonstrated a higher ratio of the transmitral and myocardial peak early diastolic velocities (E/Em) (10.50 ± 3.18 vs. 8.58 ± 2.07; P = 0.008), and larger maximal LA volume index (LAVi) (29.60 ± 9.89 vs. 20.07 ± 4.76 ml/m(2); P<0.001) compared with controls. Stage III patients had decreased LV global longitudinal systolic strain (LV?) compared with controls (-20.2 ± 3.06 vs. -21.79 ± 2.27; P = 0.002). Stage III patients also had decreased peak atrial longitudinal strain rate during ventricular systole (ALSR(syst)), peak atrial longitudinal strain rate during ventricular early diastole (ALSR(early)), and peak atrial longitudinal strain rate during ventricular late diastole (ALSR(late)) compared with controls (1.73 ± 0.48 vs. 2.05 ± 0.55 1/s, -1.44 ± 0.53 vs. -2.07 ± 0.84 1/s, -2.07 ± 0.7 vs. -2.66 ± 0.91 1/s, respectively; all P<0.005). Multiple regression analysis revealed severity of gout had an independent negative impact on LA pump function (ALSR(late)). In conclusion, gout caused LV diastolic dysfunction, LV subclinical systolic dysfunction and LA reservoir, conduit, and booster pump dysfunction.
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Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol?=?12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 ?M doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.
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Differential site accessibility mechanistically explains subcellular-specific N-glycosylation determinants.
Front Immunol
PUBLISHED: 01-01-2014
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Glycoproteins perform extra- and intracellular functions in innate and adaptive immunity by lectin-based interactions to exposed glyco-determinants. Herein, we document and mechanistically explain the formation of subcellular-specific N-glycosylation determinants on glycoproteins trafficking through the shared biosynthetic machinery of human cells. LC-MS/MS-based quantitative glycomics showed that the secreted glycoproteins of eight human breast epithelial cells displaying diverse geno- and phenotypes consistently displayed more processed, primarily complex type, N-glycans than the high-mannose-rich microsomal glycoproteins. Detailed subcellular glycome profiling of proteins derived from three breast cell lines (MCF7/MDA468/MCF10A) demonstrated that secreted glycoproteins displayed significantly more ?-sialylation and ?1,6-fucosylation, but less ?-mannosylation, than both the intermediately glycan-processed cell-surface glycoproteomes and the under-processed microsomal glycoproteomes. Subcellular proteomics and gene ontology revealed substantial presence of endoplasmic reticulum resident glycoproteins in the microsomes and confirmed significant enrichment of secreted and cell-surface glycoproteins in the respective subcellular fractions. The solvent accessibility of the glycosylation sites on maturely folded proteins of the 100 most abundant putative N-glycoproteins observed uniquely in the three subcellular glycoproteomes correlated with the glycan type processing thereby mechanistically explaining the formation of subcellular-specific N-glycosylation. In conclusion, human cells have developed mechanisms to simultaneously and reproducibly generate subcellular-specific N-glycosylation using a shared biosynthetic machinery. This aspect of protein-specific glycosylation is important for structural and functional glycobiology and discussed here in the context of the spatio-temporal interaction of glyco-determinants with lectins central to infection and immunity.
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Single nucleotide polymorphisms associated with colorectal cancer susceptibility and loss of heterozygosity in a Taiwanese population.
PLoS ONE
PUBLISHED: 01-01-2014
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Given the significant racial and ethnic diversity in genetic variation, we are intrigued to find out whether the single nucleotide polymorphisms (SNPs) identified in genome-wide association studies of colorectal cancer (CRC) susceptibility in East Asian populations are also relevant to the population of Taiwan. Moreover, loss of heterozygosity (LOH) may provide insight into how variants alter CRC risk and how regulatory elements control gene expression. To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants and their relevance to the Taiwanese population, we genotyped 705 CRC cases and 1,802 healthy controls (Taiwan Biobank) for fifteen previously reported East Asian CRC-susceptibility SNPs and four novel genetic variants identified by whole-exome sequencing. We found that rs10795668 in FLJ3802842 and rs4631962 in CCND2 were significantly associated with CRC risk in the Taiwanese population. The previously unreported rs1338565 was associated with a significant increased risk of CRC. In addition, we also genotyped tumor tissue and paired adjacent normal tissues of these 705 CRC cases to search for LOH, as well as risk-associated and protective alleles. LOH analysis revealed preferential retention of three SNPs, rs12657484, rs3802842, and rs4444235, in tumor tissues. rs4444235 has been recently reported to be a cis-acting regulator of BMP4 gene; in this study, the C allele was preferentially retained in tumor tissues (p?=?0.0023). rs4631962 and rs10795668 contribute to CRC risk in the Taiwanese and East Asian populations, and the newly identified rs1338565 was specifically associated with CRC, supporting the ethnic diversity of CRC-susceptibility SNPs. LOH analysis suggested that the three CRC risk variants, rs12657484, rs3802842, and rs4444235, exhibited somatic allele-specific imbalance and might be critical during neoplastic progression.
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Culture qualitatively but not quantitatively influences performance in the Boston naming test in a chinese-speaking population.
Dement Geriatr Cogn Dis Extra
PUBLISHED: 01-01-2014
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The Boston Naming Test (BNT) is the most frequently administered confrontational naming test, but the cultural background of the patients may influence their performance in the BNT. The aim of this study was to identify differences in performance in the BNT between a Chinese population in Taiwan, Chinese populations in other areas and a Caucasian population.
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Premature CD4+ T cell aging and its contribution to lymphopenia-induced proliferation of memory cells in autoimmune-prone non-obese diabetic mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Lymphopenia-induced proliferation (LIP), a mechanism to maintain a constant number of T cells in circulation, occurs in both normal aging and autoimmune disease. The incidence of most autoimmune diseases increases with age, and premature CD4(+) T cell aging has been reported in several autoimmune diseases. In this study, we tested the hypothesis that premature CD4(+) T cell aging can cause autoimmune disease by examining whether premature CD4(+) T cell aging exists and causes LIP in our mouse model. Non-obese diabetic (NOD) mice were used because, in addition to Treg defects, the LIP of T cells has been shown to plays a causative role in the development of insulin-dependent diabetes mellitus (IDDM) in these mice. We found that with advancing age, NOD mice exhibited an accelerated decrease in the number of CD4(+) T cells due to the loss of naïve cells. This was accompanied by an increase in the percentage of memory cells, leading to a reduced naïve/memory ratio. In addition, both the percentage of CD28(+) cells in CD4(+) T cells and IL-2 production decreased, while the percentage of FAS(+)CD44(+) increased, suggesting that NOD mice exhibit premature CD4(+) T cell aging. This process preferentially contributed to LIP of memory cells. Therefore, our results suggest that premature CD4(+) T cell aging underlies the development of IDDM in NOD mice. Given that CD28 and IL-2 play important roles in Treg function, the relationships between premature CD4(+) T cell aging and lymphopenia as well as Treg defects in autoimmune-prone NOD mice are proposed.
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A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients.
PLoS ONE
PUBLISHED: 01-01-2014
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The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.
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A Review of the Impact of Preoperative Chemoradiotherapy on Outcome and Postoperative Complications in Esophageal Cancer Patients.
Am. J. Clin. Oncol.
PUBLISHED: 12-20-2013
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Preoperative chemoradiotherapy has emerged in the treatment of esophageal cancer as a means to down-stage tumors, improve local control, and possibly improve overall survival. However, there are concerns that postoperative complications may be increased by preoperative chemoradiotherapy. We review the rationale for preoperative chemoradiotherapy. We review the literature to identify the potential postoperative complications, the risk of complications, and the risk factors for complications. Although individual and previous studies have shown an increased risk of postoperative complications, the 4 most recent randomized trials published after the year 2000 have not shown an increase in postoperative complications and mortality rates in patients treated with preoperative chemoradiation compared with patients treated with surgery alone. Pulmonary complications are frequently reported, and we focus on dosimetric factors that can be used to minimize lung toxicity. Several dose-volume-histogram parameters, including V10?40%, V15?30%, V20?20%, have been shown to correlate with 32% to 35% of pulmonary complications including pneumonia and acute respiratory distress syndrome. More recent evidence has suggested that an absolute volume of lung spared doses of > 5 Gy (VS5) correlates with pulmonary complications. As these data show, low-dose volume may be more important in the prevention of pulmonary complications than high-dose volume. These dosimetric constraints can be used by physicians to prevent postoperative pulmonary complications in patients treated with preoperative chemoradiotherapy.
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[Progress of researches on specificity of acupoints in China in recent 10 years].
Zhen Ci Yan Jiu
PUBLISHED: 11-23-2013
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After searching for literature about the specificity of acupoints from China National Knowledge Infrastructure (CNKI) database (in Chinese) and MEDLINE (in English), published by Chinese scholars from June 2003 to June 2012, the authors made a systemic analysis on the retrieved papers. It was found that most Chinese scholars took a positive viewpoint about the specificity of acupoints in morphological structure, biophysical characters, pathological reactions, acupuncture stimulation-induced responses in different brain regions and therapeutic effects. However, the research methods and comprehensive analysis of abundant research results need being improved, and the conclusion should be validated extensively. Moreover, the research on the affecting factors of specificity of acupoints will be one of the major directions.
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Krüppel-like factor 5 associates with melamine-cyanurate crystal-induced nephritis in rats.
Nephrol. Dial. Transplant.
PUBLISHED: 10-01-2013
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Melamine and cyanuric acid (M/CA), when orally administered together to rats, can induce crystal formation within renal tubules and cause acute kidney injury.
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Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.
World J. Gastroenterol.
PUBLISHED: 09-29-2013
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High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/?-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.
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BPR0C305, an orally active microtubule-disrupting anticancer agent.
Anticancer Drugs
PUBLISHED: 09-13-2013
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BPR0C305 is a novel N-substituted indolyl glyoxylamide previously reported with in-vitro cytotoxic activity against a panel of human cancer cells including P-gp-expressing multiple drug-resistant cell sublines. The present study further examined the underlying molecular mechanism of anticancer action and evaluated the in-vivo antitumor activities of BPR0C305. BPR0C305 is a novel synthetic small indole derivative that demonstrates in-vitro activities against human cancer cell growth by inhibiting tubulin polymerization, disrupting cellular microtubule assembly, and causing cell cycle arrest at the G2/M phase. It is also orally active against leukemia and solid tumor growths in mouse models. Findings of these pharmacological and pharmacokinetic studies suggest that BPR0C305 is a promising lead compound for further preclinical developments.
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A Novel Cancer Therapeutic Using Thrombospondin 1 in Dendritic Cells.
Mol. Ther.
PUBLISHED: 08-29-2013
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Induction of thrombospondin 1 (TSP-1) is generally assumed to suppress tumor growth through inhibiting angiogenesis; however, it is less clear how TSP-1 in dendritic cells (DCs) influences tumor progression. We investigated tumor growth and immune mechanism by downregulation of TSP-1 in dendritic cells. Administration of TSP-1 small hairpin RNA (shRNA) through the skin produced anticancer therapeutic effects. Tumor-infiltrating CD4(+) and CD8(+) T cells were increased after the administration of TSP-1 shRNA. The expression of interleukin-12 and interferon-? in the lymph nodes was enhanced by injection of TSP-1 shRNA. Lymphocytes from the mice injected with TSP-1 shRNA selectively killed the tumor cells, and the cytotoxicity of lymphocytes was abolished by depletion of CD8(+) T cells. Injection of CD11c(+) TSP-1-knockout (TSP-1-KO) bone marrow-derived DCs (BMDCs) delayed tumor growth in tumor-bearing mice. Similarly, antitumor activity induced by TSP-1-KO BMDCs was abrogated by depletion of CD8(+) T cells. In contrast, the administration of shRNAs targeting TSP-2, another TSP family member, did not extend the survival of tumor-bearing mice. Finally, TSP-1 shRNA functioned as an immunotherapeutic adjuvant to augment the therapeutic efficacy of Neu DNA vaccination. Collectively, the downregulation of TSP-1 in DCs produces an effective antitumor response that is opposite to the protumor effects by silencing of TSP-1 within tumor cells.Molecular Therapy (2013); doi:10.1038/mt.2013.236.
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[Progress on research of specificity of acupoint effects during "the 11th five-year"].
Zhongguo Zhen Jiu
PUBLISHED: 08-24-2013
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With retrieval in CNKI and MEDLINE data base, the articles in Chinese and English that were written by Chinese authors, which were about the specificity of acupoint effects during "the Eleventh Five-Year (2006-2010)", are included. Researchers have studied about the specificity of acupoint effects by cerebral function imaging technique and it turns out that from the perspective of central mechanism, there are differences among aupoint stimulatory effect. The curative effect of acupoints is significantly better than that of nonacupoints, different acupoints have different curative effects, the effect of disease-related acupoints is better than that of unrelated acupoints, those above have intitally proved the existence of specificity of acupoint effects. However, part of the research results need futher summaries, analysis and promotion as well as try to avoid low-level repeat in research design.
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Factors associated with use of preoperative chemoradiation therapy for rectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium.
Am. J. Clin. Oncol.
PUBLISHED: 08-24-2013
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Preoperative (preop) chemoradiation therapy (CRT) improves local control and reduces toxicity more than postoperative (postop) CRT for the treatment of stages II/III rectal cancer, but studies suggest that many patients still receive postop CRT. We examined patient beliefs and clinical and provider characteristics associated with receipt of recommended therapy.
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Facile removal of high mannose structures prior to extracting complex type N-glycans from de-N-glycosylated peptides retained by C18 solid phase to allow more efficient glycomic mapping.
Proteomics
PUBLISHED: 08-06-2013
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The relative amount of high mannose structures within an N-glycomic pool differs from one source to another, but quite often it predominates over the larger size complex type structures carrying biologically important glyco-epitopes. An efficient method to separate these two classes of N-glycans would significantly aid in detecting the lower abundant components by MS. Capitalizing on an initial observation that only high mannose type structures were recovered in the flow-through fraction when peptide-N-glycosidase F digested peptides were passed through a C18 cartridge in 0.1% formic acid, we demonstrated here that native complex type N-glycans can be retained by C18 cartridge and to be efficiently separated from both the smaller high mannose type structures, as well as de-N-glycosylated peptides by stepwise elution with increasing ACN concentration. The weak retention of the largely hydrophilic N-glycans on C18 resin is dependent not only on size but also increased by the presence of ?6-fucosylation. This was shown by comparing the resulting N-glycomic profiles of the washed and low-ACN eluted fractions derived from both a human cancer cell line and an insect cell line.
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[Discussion on the influence of factors related organic on Deqi in acupuncture treatment].
Zhongguo Zhen Jiu
PUBLISHED: 07-04-2013
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To discuss the influence of factors related organic on deqi in acupuncture treatment and provide scientific evidence for further research on the influencing factors of deqi sensation.
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[Review of studies on Deqi of acupuncture mainly in foreign countries].
Zhen Ci Yan Jiu
PUBLISHED: 07-04-2013
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Deqi (needle sensation), is closely related to clinical therapeutic effect of acupuncture in the treatment of different clinical conditions. In the present paper, the authors summarized various components or concepts of Deqi mainly in the foreign studies collected from Pubmed database. At present, foreign researches about Deqi mainly include 1) the subjects subjective qualitative and quantitative descriptions about Deqi, 2) correlation between acupuncture stimulation induced Deqi and clinical therapeutic effects, and 3) responses of different brain regions or the connectivity of brain network shown by functional magnetic resonance imaging (fMRI) during Deqi by needling different acupoints. According to the current commonly used 6 questionnaires, aching, tingling, numbness, heaviness, dull pain, throbbing, and deep pressure sensation are the most frequently seen components of Deqi of acupuncture stimulation. The factors influencing Deqi are psychological state, personal previous experience and cultural background. Regarding the degree of Deqi and clinical effects or outcomes, the conclusions are controversial.
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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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