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Find video protocols related to scientific articles indexed in Pubmed.
The use of EGFR inhibitors in colorectal cancer: is it clinically efficacious and cost-effective?
Expert Rev Pharmacoecon Outcomes Res
PUBLISHED: 11-18-2014
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Cetuximab (Erbitux) and panitumumab (Vectibix) are monoclonal antibodies to the EGFR. They are used as monotherapy or in combination with cytotoxic chemotherapy and increase both progression-free survival and overall survival in patients with wild-type RAS metastatic colorectal cancer. The most common side effects of therapy are dermatological, including skin (acneiform) rash, pruritus and hair changes. Despite their clinical activity, cost-effectiveness of the two drugs should be addressed in a discussion of their usage in everyday care. This study provides an up-to-date review of the clinical efficacy and cost-effectiveness of anti-EGFR inhibitors.
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A systematic literature analysis of correlative studies in low-dose metronomic chemotherapy trials.
Biomark Med
PUBLISHED: 09-17-2014
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Low-dose metronomic (LDM) chemotherapy is a beneficial and very well-tolerated form of chemotherapy utilization characterized by the frequent and uninterrupted administration of low doses of conventional chemotherapeutic agents over prolonged periods of time. While patients resistant to standard maximum tolerated dose (MTD) chemotherapy may still benefit from LDM chemotherapy, there is a lack of predictive markers of response to LDM chemotherapy. We searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for correlative studies conducted as part of LDM chemotherapy trials in order to identify the most promising biomarker candidates. Given the antiangiogenic properties of LDM chemotherapy, angiogenesis-related biomarkers were most commonly studied. However, significant correlations between angiogenesis-related biomarkers and study end points were rare and variable, even so far as biomarkers correlating positively with an end point in some studies and negatively with the same end point in other studies. Pursuing biomarkers outside the angiogenesis field may be more promising.
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Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.
Nat. Genet.
PUBLISHED: 06-27-2014
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In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
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Chest Radiological Findings of Patients With Severe H1N1 Pneumonia Requiring Intensive Care.
J Intensive Care Med
PUBLISHED: 06-14-2014
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A new strain of human influenza A (H1N1) virus originated from Mexico in 2009 and spread to more than 190 countries and territories. The World Health Organization (WHO) declared it a level 6 (highest level) pandemic. In August 2010, WHO announced that the H1N1 2009 influenza virus had moved into the postpandemic period. The WHO also declared that this flu strain is expected to continue to circulate as a seasonal virus "for some years to come." The objective of this study is to describe the chest radiographic and computed tomography (CT) findings of patients with severe H1N1 pneumonia admitted to the intensive care unit (ICU) during the 2009 pandemic.
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Spread of X inactivation on chromosome 15 is associated with a more severe phenotype in a girl with an unbalanced t(X; 15) translocation.
Am. J. Med. Genet. A
PUBLISHED: 05-22-2014
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We report on a baby girl with multiple congenital abnormalities, including cleft palate, intrauterine growth restriction, and double outlet right ventricle (DORV) with ventricular septal defect. She had an unbalanced chromosome translocation t (X;15) resulting in monosomy 15pter ? p10 and trisomy Xq13.1 ? q28. All three copies of Xq encompass the XIST gene. It is known that X chromosome inactivation could spread to the autosome part of an unbalanced translocation involving chromosome X and an autosome. To confirm the spread of X chromosome inactivation on chromosome 15, we evaluate the methylation change by the HumanMethylation450 BeadChip, a whole genome DNA methylation micorarray that includes 15,259 probes spanning 717 genes on chromosome 15. Results showed there was gain in DNA methylation of more than 20% in 586 CpG sites spanning the long arm of chromosome 15. We further examined the hypermethylated CpG sites located in CpG-island promoter, because genes subjected to X chromosome inactivation will have an increase in DNA methylation level in this region. A total of 75 sites representing 24 genes were hypermethylated. Nearly all of these probes are located in region proximal to the breakpoint, from 15q11.2 to 15q21.3 (35Mb) suggesting that X inactivation was spread to the proximal region of 15q. Gain of DNA methylation, especially in the CpG-island promoter, can result in functional inactivation of genes, and therefore could potentially worsen the phenotype of our patient.
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Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care.
Eur J Med Genet
PUBLISHED: 03-19-2014
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22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Under-diagnosis in adults is common and recognition of facial dysmorphic features can be affected by age and ethnicity. This study aims to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients with conotruncal anomalies and to delineate their facial dysmorphisms and extra-cardiac manifestations. We recruited consecutively 156 patients with conotruncal anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ hybridization. Assessment for dysmorphic features was performed by a cardiologist at initial screening and then by a clinical geneticist upon result disclosure. Clinical photographs were taken and childhood photographs collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal anomalies. While dysmorphic features were detected by our clinical geneticist in all patients, only two-thirds were considered dysmorphic by our cardiologist upon first assessment. Evolution of facial dysmorphic features was noted with age. Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal defects is common and facial dysmorphic features may not be reliably recognized in the setting of adult CHD clinic, referral for genetic evaluation and molecular testing for 22q11.2DS should be offered to patients with conotruncal defects.
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Genomic testing in cancer: patient knowledge, attitudes, and expectations.
Cancer
PUBLISHED: 02-24-2014
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Genomic testing in cancer (GTC) characterizes genes that play an important role in the development and growth of a patient's cancer. This form of DNA testing is currently being studied for its ability to guide cancer therapy. The objective of the current study was to describe patients' knowledge, attitudes, and expectations toward GTC.
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Outcomes of intensity-modulated radiotherapy versus conventional radiotherapy for hypopharyngeal cancer.
Head Neck
PUBLISHED: 02-24-2014
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The purpose of this study was to discuss if the adoption of intensity-modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC) has improved the outcome.
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Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials.
Support Care Cancer
PUBLISHED: 02-17-2014
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Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT(3)RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT(3)RAs in CINV prophylaxis.
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A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-12-2014
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To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases.
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Differentiating Puerariae Lobatae Radix and Puerariae Thomsonii Radix using HPTLC coupled with multivariate classification analyses.
J Pharm Biomed Anal
PUBLISHED: 02-10-2014
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Puerariae Lobatae Radix (PLR), the root of Pueraria lobata, is a traditional Chinese medicine for treating diabetes and cardiovascular diseases. Puerariae Thomsonii Radix (PTR), the root of Pueraria thomsonii, is a closely related species to PLR and has been used as a PLR substitute in clinical practice. The aim of this study was to compare the classification accuracy of high performance thin-layer chromatography (HPTLC) with that of ultra-performance liquid chromatography (UPLC) in differentiating PLR from PTR. The Matlab functions were used to facilitate the digitalisation and pre-processing of the HPTLC plates. Seven multivariate classification methods were evaluated for the two chromatographic methods. The results demonstrated that the HPTLC classification models were comparable to the UPLC classification models. In particular, k-nearest neighbours, partial least square-discriminant analysis, principal component analysis-discriminant analysis and support vector machine-discriminant analysis showed the highest rate of correct species classification, whilst the lowest classification rate was obtained from soft independent modelling of class analogy. In conclusion, HPTLC combined with multivariate analysis is a promising technique for the quality control and differentiation of PLR and PTR.
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Chemotherapy-induced cardiotoxicity: detection, prevention, and management.
Can J Cardiol
PUBLISHED: 01-10-2014
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Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivors. It might manifest as arrhythmia, hypertension, myocardial ischemia, thromboembolism, heart failure, systolic dysfunction, or other adverse events. Anthracyclines and trastuzumab are the chemotherapeutic agents with the most documented cardiac side effects; however, the array of novel molecular targeting therapies available is concerning because their side effects are not yet well understood. Nevertheless, there are potential strategies to mitigate the risks of cardiac complications for cancer patients. In this article, the common systemic drugs with cardiotoxic potential and the monitoring and diagnostic tools, including the role of biomarkers for early detection, are reviewed. We will also review the use of cardioprotectant agents as pharmacological interventions in prophylactic and treatment settings. Our aim is to provide a concise and up-to-date summary of the detection, management, and prevention of chemotherapy-induced cardiotoxicity for the busy clinician.
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The treatment of Alzheimer's disease using Chinese medicinal plants: from disease models to potential clinical applications.
J Ethnopharmacol
PUBLISHED: 01-09-2014
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Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports.
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Underestimation of uncertainties in health utilities derived from mapping algorithms involving health-related quality-of-life measures: statistical explanations and potential remedies.
Med Decis Making
PUBLISHED: 01-09-2014
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Mapping algorithms are being developed in increasing numbers to derive health utilities (HUs) from health-related quality-of-life (HRQOL) data. However, the variances of the mapping-derived HUs are observed to be smaller than those of the actual HUs.
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Gallic acid protects against endothelial injury by restoring the depletion of DNA methyltransferase 1 and inhibiting proteasome activities.
Int. J. Cardiol.
PUBLISHED: 01-07-2014
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The aim of this study was to investigate the protective effects of gallic acid, a common phenolic compound naturally present in food and nutraceuticals, on endothelial cell death and the mechanisms involved.
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Ligand-enabled cross-coupling of C(sp3)-H bonds with arylboron reagents via Pd(II)/Pd(0) catalysis.
Nat Chem
PUBLISHED: 01-05-2014
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There have been numerous developments in C-H activation reactions in the past decade. Attracted by the ability to functionalize molecules directly at ostensibly unreactive C-H bonds, chemists have discovered reaction conditions that enable reactions of C(sp(2))-H and C(sp(3))-H bonds with a variety of coupling partners. Despite these advances, the development of suitable ligands that enable catalytic C(sp(3))-H bond functionalization remains a significant challenge. Herein we report the discovery of a mono-N-protected amino acid ligand that enables Pd(II)-catalysed coupling of ?-C(sp(3))-H bonds in triflyl-protected amines with arylboron reagents. Remarkably, no background reaction was observed in the absence of ligand. A variety of amine substrates and arylboron reagents were cross-coupled using this method. Arylation of optically active substrates derived from amino acids also provides a potential route for preparing non-proteinogenic amino acids.
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The clinical impact of chromosomal microarray on paediatric care in Hong Kong.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong.
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A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear.
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Whole-genome array CGH evaluation for replacing prenatal karyotyping in Hong Kong.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong.
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Crosslinking of collagen scaffolds promotes blood and lymphatic vascular stability.
J Biomed Mater Res A
PUBLISHED: 07-23-2013
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The low stiffness of reconstituted collagen hydrogels has limited their use as scaffolds for engineering implantable tissues. Although chemical crosslinking has been used to stiffen collagen and protect it against enzymatic degradation in vivo, it remains unclear how crosslinking alters the vascularization of collagen hydrogels. In this study, we examine how the crosslinking agents genipin and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide alter vascular stability and function in microfluidic type I collagen gels in vitro. Under moderate perfusion (?10 dyn/cm(2) shear stress), tubes of blood endothelial cells (ECs) exhibited indistinguishable stability and barrier function in untreated and crosslinked scaffolds. Surprisingly, under low perfusion (?5 dyn/cm(2) shear stress) or nearly zero transmural pressure, microvessels in crosslinked scaffolds remained stable, while those in untreated gels rapidly delaminated and became poorly perfused. Similarly, tubes of lymphatic ECs under intermittent flow were more stable in crosslinked gels than in untreated ones. These effects correlated well with the degree of mechanical stiffening, as predicted by analysis of fracture energies at the cell-scaffold interface. This work demonstrates that crosslinking of collagen scaffolds does not hinder normal EC physiology; instead, crosslinked scaffolds promote vascular stability. Thus, routine crosslinking of scaffolds may assist in vascularization of engineered tissues. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Valeriana amurensis improves Amyloid-beta 1-42 induced cognitive deficit by enhancing cerebral cholinergic function and protecting the brain neurons from apoptosis in mice.
J Ethnopharmacol
PUBLISHED: 06-24-2013
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Valeriana amurensis, a perennial medicinal herb, has been widely used as anxiolytic, antidepressant, antispasmodic, and sedative in traditional Chinese medicines (TCMs). Moreover, it has been used to treat dementia in Mongolia preparations. In our previous study, we reported that AD-effective fraction of Valeriana amurensis (AD-EFV) has protective effect on A?-induced toxicity in PC12 cells. Up to now, however, the therapeutic effect of Valeriana amurensis on Alzheimer disease (AD) has not been explored. This study was designed to determine whether the AD-EFV could improve the Amyloid-beta (A?)-induced cognitive deficit and to explore the mechanism of AD-EFV improves cognitive deficit in intact animals.
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Chinese herbal medicines for hypertriglyceridaemia.
Cochrane Database Syst Rev
PUBLISHED: 06-08-2013
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Hypertriglyceridaemia is associated with many diseases including atherosclerosis, diabetes, hypertension and chylomicronaemia. Chinese herbal medicines have been used for a long time as lipid-lowering agents.
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Granulocyte colony-stimulating factor as secondary prophylaxis of febrile neutropenia in the management of advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy: a decision analysis.
Leuk. Lymphoma
PUBLISHED: 05-29-2013
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Abstract Current practice guidelines are unclear regarding the role of secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma despite several small retrospective studies that demonstrate the omission of growth factors to be a safe and economic practice. We used a decision-analytic model to compare secondary prophylaxis with granulocyte colony-stimulating factor (G-CSF) to no G-CSF with the onset of severe neutropenia for a hypothetical cohort of patients with advanced-stage Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). There was a net benefit of 0.017 years and 0.037 quality-adjusted life years for no G-CSF use in severe neutropenia. On microsimulation (10 000 trials), 96% of the simulations showed that the no G-CSF strategy is preferred to the use of G-CSF. This finding was robust across a wide range of sensitivity analyses. Our analysis suggests that G-CSF not be used as secondary prophylaxis of febrile neutropenia in advanced-stage Hodgkin lymphoma.
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A Prenatal Case of Split-hand Malformation Associated with 17p13.3 triplication - A dilemma in genetic counselling.
Eur J Med Genet
PUBLISHED: 05-13-2013
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Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound. Array comparative genomic hybridization detected 2 maternally inherited copy number gains in the 17p13.3 region with one of them involving the BHLHA9 gene and part of the YWHAE gene. The mother is normal in intelligence with mild right foot anomaly only. Although the BHLHA9 copy gain is known to be associated with split-hand-foot malformation, the penetrance and expressivity is highly variable. More challenging is the effect of partial YWHAE copy number gain on neurodevelopment is inconclusive based on current literature. This case highlights the difficulties of prenatal genetic counselling in array comparative genomic hybridization findings in clinical situation with incomplete understanding of genotype-phenotype correlation.
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Differentiation of Pueraria lobata and Pueraria thomsonii using partial least square discriminant analysis (PLS-DA).
J Pharm Biomed Anal
PUBLISHED: 04-06-2013
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The aims of the study were to differentiate Pueraria lobata from its related species Pueraria thomsonii and to examine the raw herbal material used in manufacturing kudzu root granules using partial least square discriminant analysis (PLS-DA). Sixty-four raw materials of P. lobata and P. thomsonii and kudzu root-labelled granules were analysed by ultra performance liquid chromatography. To differentiate P. lobata from P. thomsonii, PLS-DA models using the variables selected from the entire chromatograms, genetic algorithm (GA), successive projection algorithm (SPA), puerarin alone and six selected peaks were employed. The models constructed by GA and SPA demonstrated superior classification ability and lower models complexity as compared to the model based on the entire chromatographic matrix, whilst the model constructed by the six selected peaks was comparable to the entire chromatographic model. The model established by puerarin alone showed inferior classification ability. In addition, the PLS-DA models constructed by the entire chromatographic matrix, GA, SPA and the six selected peaks showed that four brands out of seventeen granules were mislabelled as P. lobata. In conclusion, PLS-DA is a promising procedure for differentiating Pueraria species and determining raw material used in commercial products.
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Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma.
Clin. Cancer Res.
PUBLISHED: 03-04-2013
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Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status. Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls.
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Palladium(0)-catalyzed alkynylation of C(sp3)-H bonds.
J. Am. Chem. Soc.
PUBLISHED: 02-25-2013
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The alkynylation of ?-C(sp(3))-H bonds in aliphatic amides with alkynyl halides has been enabled using Pd(0)/N-heterocyclic carbene (NHC) and Pd(0)/phosphine (PR3) catalysts. This is the first example of utilizing [AlkynylPd(II)L(n)] complexes to activate C(sp(3))-H bonds.
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Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes.
Circ Arrhythm Electrophysiol
PUBLISHED: 02-07-2013
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Human embryonic stem cells (hESCs) can be efficiently and reproducibly directed into cardiomyocytes (CMs) using stage-specific induction protocols. However, their functional properties and suitability for clinical and other applications have not been evaluated.
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Expanded Prader-Willi syndrome due to chromosome 15q11.2-14 deletion: report and a review of literature.
Am. J. Med. Genet. A
PUBLISHED: 01-25-2013
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We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23?Mb deletion within 15q11.2-q14 and a 25.12?kb deletion in 5pter. The 15q11.2-q14 deletion encompassed the 15q11.2-q13 Prader-Willi syndrome (PWS) critical region and the recently described 15q13.3 microdeletion syndrome region while the 5pter deletion contained no RefSeq genes. From our literature review, patients with similar deletions in chromosome 15q exhibit expanded phenotype of severe developmental delay, protracted feeding problem, absent speech, central visual impairment, congenital malformations and epilepsy in addition to those typical of PWS. The patient reported herein had previously unreported anomalies of mega cisterna magna, horseshoe kidney and the rare neonatal interstitial lung disease known as pulmonary interstitial glycogenosis. Precise breakpoint delineation by microarray is useful in patients with atypical PWS deletions to guide investigation and prognostication.
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Temporal and spatial regulation of glucomannan deposition and mobilization in corms of Amorphophallus konjac (Araceae).
Am. J. Bot.
PUBLISHED: 01-24-2013
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Konjac glucomannan (KGM), the main biologically active constituent of konjac flour extracted from corms of Amorphophallus konjac (konjac), has potential to be used as a nutraceutical (satiety agent) to combat obesity. Here we present the results of an immunocytochemical investigation of the developmental regulation of the deposition and mobilization of glucomannan in corm tissues of konjac, using an antiheteromannan (mannan/glucomannan) antiserum.
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Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines.
J Ethnopharmacol
PUBLISHED: 01-05-2013
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While there is an increasing number of toxicity report cases and toxicological studies on Chinese herbal medicines, the guidelines for toxicity evaluation and scheduling of Chinese herbal medicines are lacking.
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Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish.
Neurosci. Lett.
PUBLISHED: 01-03-2013
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The overproduction of reactive oxygen species (ROS) has been implicated in the development of neurodegenerative diseases such as Parkinsons disease (PD) and Alzheimers disease (AD). Previous studies have indicated that danshensu (beta-3,4-dihydroxyphenyl-lactic acid), a main hydrophilic component of the Chinese materia medica Radix Salviae Miltiorrhizae (Danshen, Pharmacopoeia of PR China), has ROS scavenging and antioxidant activities, however its mechanism of action was not clear. In this study, we investigated whether the protective effects of danshensu against neurotoxin 6-hydroxydopamine (6-OHDA)-induced oxidative stress involved the Nrf2/HO-1 pathways. Pretreatment with danshensu in PC12 cells significantly attenuated 6-OHDA-induced cytotoxicity and the production of ROS. Danshensu activated the nuclear translocation of Nrf2 to increase heme oxygenase-1 (HO-1), conferring protection against ROS. Danshensu induced the phosphorylation of Akt, and its cytoprotective effect was abolished by PI3K, Akt and HO-1 inhibitors. These results confirmed the crucial role of PI3K/Akt and HO-1 signaling pathways as the underlying mechanistic action of danshensu. Taken together, the results suggest that danshensu enhances HO-1 expression to suppress 6-OHDA-induced oxidative damage via PI3K/Akt/Nrf2 signaling pathways. Moreover, 6-OHDA-induced dopaminergic neuronal loss in zebrafish could be reduced by danshensu, further supporting the neuroprotective potential of danshensu.
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Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics.
J. Gen. Physiol.
PUBLISHED: 01-02-2013
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Understanding the basis for differential responses to drug therapies remains a challenge despite advances in genetics and genomics. Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to investigate the pharmacology of disease processes in therapeutically and genetically relevant primary cell types in vitro and to interweave clinical and basic molecular data. We report here the derivation of iPSCs from a long QT syndrome patient with complex genetics. The proband was found to have a de novo SCN5A LQT-3 mutation (F1473C) and a polymorphism (K897T) in KCNH2, the gene for LQT-2. Analysis of the biophysics and molecular pharmacology of ion channels expressed in cardiomyocytes (CMs) differentiated from these iPSCs (iPSC-CMs) demonstrates a primary LQT-3 (Na(+) channel) defect responsible for the arrhythmias not influenced by the KCNH2 polymorphism. The F1473C mutation occurs in the channel inactivation gate and enhances late Na(+) channel current (I(NaL)) that is carried by channels that fail to inactivate completely and conduct increased inward current during prolonged depolarization, resulting in delayed repolarization, a prolonged QT interval, and increased risk of fatal arrhythmia. We find a very pronounced rate dependence of I(NaL) such that increasing the pacing rate markedly reduces I(NaL) and, in addition, increases its inhibition by the Na(+) channel blocker mexiletine. These rate-dependent properties and drug interactions, unique to the probands iPSC-CMs, correlate with improved management of arrhythmias in the patient and provide support for this approach in developing patient-specific clinical regimens.
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A novel approach in discovering significant interactions from TCM patient prescription data.
Int J Data Min Bioinform
PUBLISHED: 09-30-2011
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The efficacy of a traditional Chinese medicine medication derives from the complex interactions of herbs or Chinese Materia Medica in a formula. The aim of this paper is to propose a new approach to systematically generate combinations of interacting herbs that might lead to good outcome. Our approach was tested on a data set of prescriptions for diabetic patients to verify the effectiveness of detected combinations of herbs. This approach is able to detect effective higher orders of herb-herb interactions with statistical validation. We present an exploratory analysis of clinical records using a pattern mining approach called Interaction Rules Mining.
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Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.
Hum. Mol. Genet.
PUBLISHED: 09-09-2011
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Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
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Early mortality and overall survival in oncology phase I trial participants: can we improve patient selection?
BMC Cancer
PUBLISHED: 07-10-2011
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Patient selection for phase I trials (PIT) in oncology is challenging. A typical inclusion criterion for PIT is life expectancy > 3 months, however the 90 day mortality (90DM) and overall survival (OS) of patients with advanced solid malignancies are difficult to predict.
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Genome-wide association study of hepatocellular carcinoma in Southern Chinese patients with chronic hepatitis B virus infection.
PLoS ONE
PUBLISHED: 06-17-2011
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One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (OR(combined) = 1.31-1.39; p(combined) = 2.71 × 10(-5)-5.19 × 10(-4); PAR(combined) = 26-31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis.
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Pd-catalyzed intermolecular C-H amination with alkylamines.
J. Am. Chem. Soc.
PUBLISHED: 05-02-2011
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C-H amination of N-aryl benzamides with O-benzoyl hydroxylamines has been achieved with either Pd(II) or Pd(0) catalysts. Furthermore, we demonstrate that secondary amines can be directly used with benzoyl peroxide in a one-pot procedure that proceeds via the in situ generation of the appropriate O-benzoyl hydroxylamines. This catalytic reaction provides a new disconnection for the convergent synthesis of tertiary and secondary arylalkyl amines starting from benzoic acids.
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Very late stent thrombosis due to DES fracture: description of a case and review of potential causes.
Catheter Cardiovasc Interv
PUBLISHED: 04-28-2011
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Stent fracture and subsequent stent thrombosis are known complications after stent implantation, especially in stents with closed cell design like the first generation sirolimus drug eluting stents (DES). Late stent thrombosis is very rarely encountered in our patient population, majority Chinese. We report a case of non-ST elevation myocardial infarction as a result of very late stent thrombosis (three years after implantation) due to stent fracture at the site of overlap of two first generation sirolimus DES. There were initial difficulties in restoring coronary flow by conventional reperfusion therapies but a successful outcome after implantation of an endothelial progenitor cell capture stent, with no further recurrence of ischemic event after 12 months. An attempt was made to analyze all existing factors present and contributing to the stent fracture and stent thrombosis in this case, as reported in the literature.
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Acute and 16-month outcomes of a new stent: the first-in-man evaluation of the Medtronic S9 (integrity) stent.
Catheter Cardiovasc Interv
PUBLISHED: 04-27-2011
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A first-in-man evaluation of the safety, feasibility, deliverability, and efficacy of the new Medtronic S9 (Integrity) bare metal stent (BMS) in complex coronary diseases.
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Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.
Cochrane Database Syst Rev
PUBLISHED: 04-15-2011
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Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.
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The role of Chinese medicine in the treatment of chronic diseases in China.
Planta Med.
PUBLISHED: 04-06-2011
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Chinese medicine (CM) has a long history of experience and proven successful treatment for chronic diseases and has also played an important role in the provision of health care in China. Patients with chronic diseases are happy to accept CM and physicians are willing to use CM to relieve patients suffering from chronic illnesses. The Chinese health authorities encourage CM development to meet the requirements for the treatment of chronic diseases. CM products are an essential part of medications that have a predominant role in the prevention and treatment of chronic diseases in China. A large number of CM clinical studies, including a substantial number of available randomized controlled trials and systematic reviews, have shown that CM is effective and safe in the treatment of chronic diseases. Although the efficacies of some evaluated CM therapies remain uncertain, it is worth assessing them by using CM pattern (Zheng or syndrome) differentiation to verify treatment outcomes. CM is considered to have a better safety profile compared to pharmaceutical chemicals, but inappropriate applications of CM also makes the safety issues a hot discussed subject. As a medical system, CM should be able to provide worldwide contribution for the patients who are suffering from chronic diseases. The application of CM pattern classification in diagnosis with corresponding prescribed treatment using herbal formulae in the relief of chronic diseases can be linked with modern biomedical parameters (biomarkers) as treatment outcomes. These outcome parameters, together with the patients reported quality of life assessment, can provide innovative approaches for evidence-based estimation of the efficacy of CM treatment in chronic diseases.
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Prevalence and risk factors of Human Papillomavirus (HPV) infection in southern Chinese women - a population-based study.
PLoS ONE
PUBLISHED: 03-29-2011
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Persistent high-risk type Human papillomavirus (HPV) infection is recognized as a necessary cause of cervical cancer. This study aimed to compare the HPV prevalence and risk factors between women residing in Hong Kong (HK) and Guangzhou (GZ) region of China.
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An integrative approach of linking traditional Chinese medicine pattern classification and biomedicine diagnosis.
J Ethnopharmacol
PUBLISHED: 03-22-2011
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Traditional Chinese medicine (TCM) is a medical system with over 3000 years of continuous practice experience and refinement through treatment observations. The TCM pattern classification (also defined as Syndrome or Zheng differentiation) and treatment of ill health is the basis and the key concept of the TCM theory. All diagnostic and therapeutic methods in TCM are based on the differentiation of TCM pattern. TCM pattern can be considered as the TCM theoretical interpretation of the symptom profiles. Pattern classification is often used as a guideline in disease classification in TCM practice and has been recently incorporated with biomedical diagnosis, resulting in the increasing research interest of TCM pattern among various disciplines of integrative medicine. This paper describes the historical evolution on the integration of the TCM pattern classification and disease diagnosis in biomedicine, the methodology of pattern classification for diseases, efficacy of TCM practice with integration of TCM pattern classification and biomedical disease diagnosis, and the biological basis of TCM pattern. TCM pattern classification, which may lead to new findings in biological sciences, was also discussed.
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The role of Pea3 group transcription factors in esophageal squamous cell carcinoma.
Am. J. Pathol.
PUBLISHED: 03-11-2011
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The transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinase-Akt-mammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC.
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Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.
Cancer Res.
PUBLISHED: 02-08-2011
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We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10?³?], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10??], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region.
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Kudzu root: traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases.
J Ethnopharmacol
PUBLISHED: 01-25-2011
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Kudzu root (Gegen in Chinese) is the dried root of Pueraria lobata (Willd.) Ohwi, a semi-woody, perennial and leguminous vine native to South East Asia. It is often used interchangeably in traditional Chinese medicine with thomson kudzu root (Fengen in Chinese), the dried root of P. thomsonii, although the Chinese Pharmacopoeia has separated them into two monographs since the 2005 edition. For more than 2000 years, kudzu root has been used as a herbal medicine for the treatment of fever, acute dysentery, diarrhoea, diabetes and cardiovascular diseases. Both English and Chinese literatures on the traditional applications, phytochemistry, pharmacological activities, toxicology, quality control and potential interactions with conventional drugs of both species have been included in the present review. Over seventy phytochemicals have been identified in kudzu root, with isoflavonoids and triterpenoids as the major constituents. Isoflavonoids, in particular puerarin, have been used in most of the pharmacological studies. Animal and cellular studies have provided support for the traditional uses of kudzu root on cardiovascular, cerebrovascular and endocrine systems, including diabetes and its complications. Further studies to define the active phytochemical compositions, quality standards and clinical efficacy are warranted. Strong interdisciplinary collaboration to bridge the gap between traditional medicine and modern biomedical medicine is therefore needed for the development of kudzu root as an effective medicine for the management of diabetes and cardiovascular diseases.
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The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo.
Angiogenesis
PUBLISHED: 01-06-2011
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Radix Angelica sinensis is a Chinese medicinal herb that has been used extensively in the East for the treatment of cardiovascular diseases (CVDs). Angiogenesis plays an important role in the pathogenesis of CVDs. We hypothesized that Radix A. sinensis may contain angiogenesis modulators. In the current study, we investigated the effects of a volatile oil of Radix A. sinensis (VOAS) and n-butylidenephthalide (BP), one of the bioactive components in VOAS, on angiogenesis in vitro and in vivo. The results suggested that VOAS exerted anti-angiogenic effects by inhibiting human umbilical vein endothelial cell proliferation, migration and capillary-like tube formation on Matrigel. BP was also shown to be anti-angiogenic and its mechanisms were through inhibition of cell cycle progression and induction of apoptosis. Western blotting analysis indicated that the anti-angiogenic actions of BP were associated with the activation of p38 and ERK 1/2 but not SAPK/JNK and Akt signaling pathways. Further investigations showed that BP inhibited endothelial sprouting in an ex vivo mouse aortic ring model and was a potent inhibitor of the development of zebrafish subintestinal vessels in vivo. Our data using the volatile oil contrast with previous findings, which showed an aqueous extract of Radix A. sinensis was pro-angiogenic. This highlights the importance of identifying pro- and anti-angiogenic substances in Radix A. sinensis, not only for the development of novel angiogenesis modulators for the treatment of CVDs, but also to ensure the proper use of Radix A. sinensis as a nutraceutical.
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Pd(II)-Catalyzed Cross-Coupling of C(sp(2) )-H Bonds and Alkyl-, Aryl- and Vinyl-Boron Reagents via Pd(II)/Pd(0) Catalysis.
Chem. Lett.
PUBLISHED: 01-01-2011
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Pd(II)-catalyzed cross-coupling of ortho-C-H bonds in benzoic acid and phenylacetic acid amides with alkyl-, aryl- and vinyl-boron reagents have been achieved via Pd(II)/Pd(0) catalysis, demonstrating the unprecedented versatility of C-H activation reactions.
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Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy.
Cochrane Database Syst Rev
PUBLISHED: 12-15-2010
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The management of advanced oral cavity and oropharyngeal cancers is problematic and has traditionally relied on surgery and radiotherapy, both of which are associated with substantial adverse effects. Radiotherapy has been in use since the 1950s and has traditionally been given as single daily doses. This method of dividing up the total dose, or fractionation, has been modified over the years and a variety of approaches have been developed with the aim of improving survival whilst maintaining acceptable toxicity.
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Perspective of chemical fingerprinting of Chinese herbs.
Planta Med.
PUBLISHED: 11-09-2010
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The holistic system of traditional Chinese medicine (TCM) is an integrity of the ingredients contained in the Chinese herbal medicines, which creates a challenge in establishing quality control standards for raw materials and the standardization of finished herbal drugs because no single component is contributing to the total efficacy. Chromatographic fingerprinting analysis represents a rational approach for the quality assessment of TCM. It utilizes chromatographic techniques, which include CE, GC, HPLC, HPTLC, etc., to construct specific patterns for recognition of multiple compounds in TCMs. Thus, chromatographic fingerprinting analysis of herbal medicines represents a comprehensive qualitative approach for the purpose of species authentication, evaluation of quality, and ensuring the consistency and stability of herbal drugs and their related products. The pragmatic comprehensive chromatographic fingerprinting analysis can disclose the detectable ingredients composition and concentration distribution under quantifiable operational conditions and therefore provide real-time quality information. It may leave a "gray" entity at the primary stage. However, consecutive study will deepen the knowledge and reduce its "gray scale", increase the transparency gradually, thereby strengthening its quality assessment potency.
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A unique issue in the standardization of Chinese materia medica: processing.
Planta Med.
PUBLISHED: 11-03-2010
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Processing of Chinese Materia Medica (CMM) is a pharmaceutical technique to fulfill the different requirements of therapy, dispensing and making preparations according to traditional Chinese medicine theory. The aims of processing are to enhance the efficacy and/or reduce the toxicity of crude drugs. Those processed products are named as decoction pieces, which are used in clinics. Therefore, there is a close relationship between processing, safety, and efficacy of Chinese medicines. Some toxicity or side effects are caused by improper processing methods and some are due to improper combination of herbal mixtures. Standardization of processing methods for Chinese herbs is as important as authentication to maintain their quality and ensure their safe use. The objective of this paper is to review the literature covering the current situation and problems of CMM processing as well as recent progress in research in this area. A summary of the most urgent work needed is proposed.
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Application of mid-infrared spectroscopy in the quality control of traditional Chinese medicines.
Planta Med.
PUBLISHED: 11-03-2010
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Chinese herbal medicines are often referred to as Chinese materia medica (CMM). Composite formulae containing mixtures of CMM are prescribed for treatment and prevention of diseases in the practice of traditional Chinese medicine (TCM). Some of the well-known CMM formulae (Fufang in Chinese) are manufactured and marketed as proprietary Chinese medicines (PCM). Quality assessment and assurance of these products are difficult; they are a challenging task. Mid-infrared spectroscopy, a classic molecular structure analysis method, has been innovatively applied in the quality control of TCM, and has gained significant impact and advancement in analytical fields. Infrared fingerprinting features appear particularly suitable for the identification of multicomponent matrices in samples whose chemical integrity has not been altered or destroyed because no extraction procedure is needed. This review summarizes and gives an overall view on the application of mid-infrared and two-dimensional correlation infrared (2D-IR) spectroscopy as well as chemometric techniques in the identification of CMM, investigation of TCM processing procedures, and analysis of herb extracts and preparations.
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Clinical studies with traditional Chinese medicine in the past decade and future research and development.
Planta Med.
PUBLISHED: 10-26-2010
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Traditional Chinese medicine (TCM) is currently considered a complementary or alternative medical system in most Western countries and has been increasingly accepted worldwide. More and more clinical trials on TCM have been conducted internationally, and scientists worldwide are becoming increasingly interested in the evaluation of clinical efficacy of TCM based on clinical trials. This paper reviews the situation of clinical trials on TCM in the past decade, including systematic reviews about clinical trials either focusing on the treatment of disease with TCM approaches or focusing on one herbal product, conduction of clinical trials on TCM either with randomization and controlled methods or general observation. Some general issues on the conduct of clinical trials on TCM, such as randomization, control, quality of life (QOL), patient reported outcomes (PROs) and biomarkers, quality control, safety evaluation and case studies, are discussed, and accordingly some suggestions are proposed.
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Herbal medicines and nutraceuticals for diabetic vascular complications: mechanisms of action and bioactive phytochemicals.
Curr. Pharm. Des.
PUBLISHED: 10-07-2010
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Diabetes is one of the most prevalent chronic diseases throughout the world. The majority of its complications arise from vascular-related inflammation apparently initiated by endothelial cell injury. One cause of this injury has been attributed to hyperglycaemia-induced reactive oxygen species. Consequently, current drug developmental strategy has targeted specific inflammatory and oxidative stress pathways for the prevention of diabetic vascular complications. Herbal medicines have traditionally been used for the treatment of diabetes and its complications. In fact, current pre-clinical and clinical studies have demonstrated that many of them exhibit potent anti-inflammatory and anti-oxidative properties, and have also identified the active phytochemicals responsible for their activities. The present review summarises the latest research on the molecular mechanisms of diabetic vascular complications, and evaluates the level of scientific evidence for common herbal medicines and their bioactive phytochemicals. These agents have been shown to be effective through various mechanisms, particularly the NF-?B signalling pathways. Overall, herbal medicines and nutraceuticals, as well as their bioactive components, which exhibit anti-inflammatory and anti-oxidative properties, provide a promising approach for the prevention and treatment of diabetic complications.
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Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathway.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-20-2010
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Neurons rely on their metabolic coupling with astrocytes to combat oxidative stress. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) appears important for astrocyte-dependent neuroprotection from oxidative insults. Indeed, Nrf2 activators are effective in stroke, Parkinson disease, and Huntington disease models. However, key endogenous signals that initiate adaptive neuroprotective cascades in astrocytes, including activation of Nrf2-mediated gene expression, remain unclear. Hydrogen peroxide (H(2)O(2)) plays an important role in cell signaling and is an attractive candidate mediator of adaptive responses in astrocytes. Here we determine (i) the significance of H(2)O(2) in promoting astrocyte-dependent neuroprotection from oxidative stress, and (ii) the relevance of H(2)O(2) in inducing astrocytic Nrf2 activation. To control the duration and level of cytoplasmic H(2)O(2) production in astrocytes cocultured with neurons, we heterologously expressed the H(2)O(2)-producing enzyme Rhodotorula gracilis D-amino acid oxidase (rgDAAO) selectively in astrocytes. Exposure of rgDAAO-astrocytes to D-alanine lead to the concentration-dependent generation of H(2)O(2). Seven hours of low-level H(2)O(2) production (?3.7 nmol·min·mg protein) in astrocytes protected neurons from oxidative stress, but higher levels (?130 nmol·min·mg protein) were neurotoxic. Neuroprotection occurred without direct neuronal exposure to astrocyte-derived H(2)O(2), suggesting a mechanism specific to astrocytic intracellular signaling. Nrf2 activation mimicked the effect of astrocytic H(2)O(2) yet H(2)O(2)-induced protection was independent of Nrf2. Astrocytic protein tyrosine phosphatase inhibition also protected neurons from oxidative death, representing a plausible mechanism for H(2)O(2)-induced neuroprotection. These findings demonstrate the utility of rgDAAO for spatially and temporally controlling intracellular H(2)O(2) concentrations to uncover unique astrocyte-dependent neuroprotective mechanisms.
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Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.
Cochrane Database Syst Rev
PUBLISHED: 09-09-2010
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Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.
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Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis.
Br J Psychiatry
PUBLISHED: 09-03-2010
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Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.
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Chromatographic fingerprinting and metabolomics for quality control of TCM.
Comb. Chem. High Throughput Screen.
PUBLISHED: 06-22-2010
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Chromatographic fingerprinting technique of traditional Chinese medicine (TCM) has proved to be a comprehensive strategy for assessing the intact quality of herbal medicine. In general, one could use the chromatographic techniques to obtain a relatively complete picture of herbal medicines, which are in common called chromatographic fingerprints of herbal medicines to represent the so-called phytoequivalence. Based on this, the features of chromatographic fingerprints of herbal medicines have been discussed in some detail. The technique based on chromatographic fingerprinting is essentially a kind of high-throughput and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs, some new strategies are proposed to trace the chemical changes of chromatographic fingerprints both in product processing and/or after their administration by modern chromatographic techniques and chemometrics. Combined with metabolomics, it seems possible for one to reveal the working mechanism of TCMs and to further control their intrinsic quality. Finally, the intensive study of chromatographic fingerprinting coupled with multivariate analysis tools developed in bioinformatics and chemometrics are emphasized in order to achieve the aim to reveal the working mechanisms of TCMs and to further control and strengthen TCMs intrinsic quality in a comprehensive manner.
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Significance of the myxovirus resistance A (MxA) gene -123C>a single-nucleotide polymorphism in suppressed interferon beta induction of severe acute respiratory syndrome coronavirus infection.
J. Infect. Dis.
PUBLISHED: 05-14-2010
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Myxovirus resistance A (MxA) is an antiviral protein induced by interferon alpha and beta (IFN-alpha, IFN-beta) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-alpha and IFN-beta treatment. Here, we demonstrate that the -123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-beta-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-beta stimulation. Endogenous IFN-alpha and IFN-beta induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minor-allele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-alpha and IFN-beta induction such as SARS coronavirus.
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Constitutively nuclear FOXO3a localization predicts poor survival and promotes Akt phosphorylation in breast cancer.
PLoS ONE
PUBLISHED: 05-06-2010
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The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis.
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[Determination of free ferulic acid and total ferulic acid in Chuanxiong by high-performance liquid chromatography for quality assessment].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 04-17-2010
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Ferulic acid (FA) is one of the main bioactive compounds in Chuanxiong (CX), the dried rhizome of Ligusticum chuanxiong, but its amount in this herb is difficult to determine accurately. An accurate quantificational method was developed to investigate on the available amount of FA (free FA and total FA). Herbal samples were extracted in methanol-formic acid (95:5) and methanol-0.24 mol x L(-1) sodium hydrogen carbonate in water (95:5), respectively and then quantitatively analyzed by HPLC method. Thirty three CX samples were quantified on free and total FA. Total FA was found more abundant than free FA with an average ratio of 2.38 (n = 32) in the range of 1.03- 4.98 in 32 CX herbs, and a highest ratio of 19.6 was estimated in a rhizome seedling. Results showed that total FA content would be a better marker for the quality assessment of CX herbs. Fifteen CX typical samples were collected from the trueborn cultivating areas in Sichuan province of China. The amount of total FA in these herbs was estimated to be 1.42 mg x g(-1) (n = 15). The proposed limit of total FA in CX samples should not less than 1.25 mg x g(-1) calculated on the dried basis. It was also found that the level of total FA was related to the quality, processing method and store duration of CX samples.
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Nasopharyngeal carcinoma: the next challenges.
Eur. J. Cancer
PUBLISHED: 03-29-2010
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Nasopharyngeal carcinoma (NPC) differs from other head and neck cancers in its aetiology, epidemiology and potential therapeutic options. Despite cure for the majority of the patients, challenges still exist in the prevention of disease relapse, treatment of patients with refractory or metastatic NPC and the management of long-term toxicities. This article discusses the specific challenges in pushing the boundaries of NPC treatments further, with an emphasis on prognostic/predictive markers, molecularly targeted therapies, immunotherapies and the areas of interest with regard to long-term toxicities arising from therapeutic interventions.
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CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese.
Hum. Immunol.
PUBLISHED: 03-15-2010
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CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) -336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus-1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)-coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the -336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the -336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 -336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating.
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Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
PLoS Genet.
PUBLISHED: 02-01-2010
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Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.
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Traditional uses and potential health benefits of Amorphophallus konjac K. Koch ex N.E.Br.
J Ethnopharmacol
PUBLISHED: 01-06-2010
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Amorphophallus konjac (konjac) has long been used in China, Japan and South East Asia as a food source and as a traditional medicine. Flour extracted from the corm of this species is used in Far Eastern cuisine to make noodles, tofu and snacks. In traditional Chinese medicine (TCM), a gel prepared from the flour has been used for detoxification, tumour-suppression, blood stasis alleviation and phlegm liquefaction; and for more than 2000 years has been consumed by the indigenous people of China for the treatment of asthma, cough, hernia, breast pain, burns as well as haematological and skin disorders. Over the past two decades, purified konjac flour, commonly known as konjac glucomannan (KGM) has been introduced on a relatively small scale into the United States and Europe, both as a food additive and a dietary supplement. The latter is available in capsule form or as a drink mix and in food products. Clinical studies have demonstrated that supplementing the diet with KGM significantly lowers plasma cholesterol, improves carbohydrate metabolism, bowel movement and colonic ecology. Standards for the classification of both konjac flour and KGM have been established by the Chinese Ministry of Agriculture, the European Commission and the U.S. Food Chemicals Codex. However, to date, there is no worldwide agreed regulatory standard for konjac flour or KGM. This highlights the need for harmonization of konjac commercial standards to assess and ensure the quality of existing and future KGM products. Despite the widespread consumption of konjac derived products in East and South East Asia, there has been limited research on the biology, processing and cultivation of this species in the West. Most studies performed outside Asia have focussed on the structural characterisation and physicochemical properties of KGM. Therefore, the objective of this monograph is to review the literature covering the ethnic uses, botany and cultivation of konjac corms, together with the health benefits of KGM with the associated requirements for quality control. Possible directions for future research and development and standardisation of production and classification of this versatile natural product will be discussed.
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Review and meta-analysis of usage of ginkgo as an adjunct therapy in chronic schizophrenia.
Int. J. Neuropsychopharmacol.
PUBLISHED: 09-24-2009
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This study aimed to review the roles of antioxidants in the pathophysiology of schizophrenia, whether the properties of ginkgo can ameliorate symptoms of this illness, and evaluate available literature to test this assumption. This review is based upon published works on antioxidants and ginkgo. A primary electronic search for meta-analysis on the usage of ginkgo or its derived products in schizophrenia was conducted using Pubmed, Cochrane Library, EMBASE, CINAHL, PsycINFO and AMED. Inclusion criteria were: criteria-based diagnosis of schizophrenia, randomized case assignment, use of ginkgo as an add-on therapy, and assessment using standardized rating scales to measure the state of psychopathology for negative and total symptoms of schizophrenia. Additionally, a detailed review was undertaken to investigate if antioxidants are involved in development of psychotic symptoms in schizophrenia. The six studies that fulfilled the selection criteria were constituted of 466 cases on ginkgo and 362 cases on placebo. They all used the Scale for the Assessment of Negative Symptoms (SANS) to measure negative symptoms, and the Scale for the Assessment of Positive Symptoms (SAPS) or the Brief Psychiatric Rating Scale (BPRS) to measure total symptoms. Difference between ginkgo and control groups from their pre- and post-trial scores and its pooled standard deviation were used to compute standardized mean difference (SMD). Ginkgo as an add-on therapy to antipsychotic medication produced statistically significant moderate improvement (SMD=-0.50) in total and negative symptoms of chronic schizophrenia. Ginkgo as add-on therapy ameliorates the symptoms of chronic schizophrenia. The role of antioxidants in pathogenesis of schizophrenia has also been explored.
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Harmonization of monographic standards is needed to ensure the quality of Chinese medicinal materials.
Chin Med
PUBLISHED: 09-22-2009
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This article provides an overview on the regulations of Chinese medicinal materials (CMMs) in various countries and regions. Harmonization of CMM monographs would provide standards for the quality control of CMM products and play an important role in the modernization and globalization of Chinese medicine. A harmonized regulatory system would improve the quality of CMMs thereby ensuring the safety of the products and assisting Chinese medicine practitioners in their practice. The fast growing demand worldwide for traditional medicines calls for harmonized monographic standards to safeguard the safety and quality of CMM products.
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Quality and safety of Chinese herbal medicines guided by a systems biology perspective.
J Ethnopharmacol
PUBLISHED: 04-02-2009
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Chinese herbal medicines, often referred as Chinese materia medica (CMM), are comprised of a complex multicomponent nature. The activities are aimed at the system level via interactions with a multitude of targets in the human body. This review aims at the toxicity aspects of CMM and its preparations at the different steps of production; harvesting, processing and the final formulation. The historic perspective and todays issues of the safety of CMM are introduced briefly, followed by the descriptions of the toxic CMM in the current Chinese Pharmacopoeia (2005). Subsequently, several aspects of safety are illustrated using a typical example of a toxic CMM, Aconitum roots, and some recent findings of our own research are included to illustrate that proper processing and multi-herbs formulation can reduce the level of toxic components. This also explains that in CMM, some herbs, such as Aconitum, Ephedra species are never used as single herb for intervention and that aconite is only used when it is processed and in combination with specific matched other herbs. The formulation principle of multi-herbs intervention strategy is a systems approach for the treatment and prevention of disease. In this light, the role of systems toxicology in the safety and quality of Chinese herbal medicine is proposed as a promising method. Moreover the principles of practiced-based and evidence-based research are discussed from a symbiotic perspective.
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