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Find video protocols related to scientific articles indexed in Pubmed.
Synthesis and Biological Evaluation of Sophoridinol Derivatives as a Novel Family of Potential Anticancer Agents.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
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Intracellular NAMPT-NAD+-SIRT1 cascade improves post-ischaemic vascular repair by modulating Notch signalling in endothelial progenitors.
Cardiovasc. Res.
PUBLISHED: 10-25-2014
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Intracellular nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis. This study investigated the role of NAMPT-mediated NAD(+) signalling in post-ischaemic vascular repair.
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Late onset temperature reduction can retard aging process in aged fish via a combined action of antioxidant system and IIS pathway.
Rejuvenation Res
PUBLISHED: 10-10-2014
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Two different mechanisms are considered to be related with aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by insulin and insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong lifespan in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late onset TR from 26oC to 22oC extends mean lifespan and maximum lifespan by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of histological aging markers senescence-associated ?-galactosidase (SA-?-Gal) in the epithelium and lipofuscin (LF) in the liver, and to reduce the protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO, both of which are the downstream regulator of IIS pathway. Taken together, our findings suggest that late onset TR, a simple non-intrusion intervention, can retard aging process in aged fish, resulting in their lifespan extension, via a synergistic action of antioxidant system and IIS pathway. This also suggests that combined assessment of ROS concept and IIS concept will contribute to providing more comprehensive view of anti-aging process.
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Decomposed fuzzy systems and their application in direct adaptive fuzzy control.
IEEE Trans Cybern
PUBLISHED: 09-16-2014
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In this paper, a novel fuzzy structure termed as the decomposed fuzzy system (DFS) is proposed to act as the fuzzy approximator for adaptive fuzzy control systems. The proposed structure is to decompose each fuzzy variable into layers of fuzzy systems, and each layer is to characterize one traditional fuzzy set. Similar to forming fuzzy rules in traditional fuzzy systems, layers from different variables form the so-called component fuzzy systems. DFS is proposed to provide more adjustable parameters to facilitate possible adaptation in fuzzy rules, but without introducing a learning burden. It is because those component fuzzy systems are independent so that it can facilitate minimum distribution learning effects among component fuzzy systems. It can be seen from our experiments that even when the rule number increases, the learning time in terms of cycles is still almost constant. It can also be found that the function approximation capability and learning efficiency of the DFS are much better than that of the traditional fuzzy systems when employed in adaptive fuzzy control systems. Besides, in order to further reduce the computational burden, a simplified DFS is proposed in this paper to satisfy possible real time constraints required in many applications. From our simulation results, it can be seen that the simplified DFS can perform fairly with a more concise decomposition structure.
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The Antiaging Activity and Cerebral Protection of Rapamycin at Micro-doses.
CNS Neurosci Ther
PUBLISHED: 09-04-2014
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The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear.
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[Biomechanical study of the influence of stability for the pedicle screws fixation by injured vertebral screw when the pedicle cortex perforation].
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 09-02-2014
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To explore the impact of pedicle cortex perforation on the stability of internal fixation of the vertebral body fracture,and to compare the stability of the vertebrae with pedicle cortex perforation after the injured vertebra transpedicular screw fixation by different ways.
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Crystal structure of diethyl [(4-nitro-phenyl-amino)(2-hy-droxy-phen-yl)meth-yl]phospho-nate methanol monosolvate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 09-01-2014
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In the title compound, C17H21N2O6P·CH3OH, the planes of the 4-nitro-aniline and 2-hy-droxy-phenyl groups form a dihedral angle of 84.04?(8)°. The P atom exhibits tetra-hedral geometry involving two O-ethyl groups, a C? atom and a double-bonded O atom. In the crystal, O-H?O, N-H?O and C-H?O hydrogen bonds link the ?-amino-phospho-nic acid and methanol mol-ecules into chains that propagate parallel to the a axis.
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Peptic ulcer as a risk factor for postherpetic neuralgia in adult patients with herpes zoster.
J. Med. Virol.
PUBLISHED: 08-22-2014
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Postherpetic neuralgia is the most common complication of herpes zoster. Identifying predictors for postherpetic neuralgia may help physicians screen herpes zoster patients at risk of postherpetic neuralgia and undertake preventive strategies. Peptic ulcer has been linked to immunological dysfunctions and malnutrition, both of which are predictors of postherpetic neuralgia. The aim of this retrospective case-control study was to determine whether adult herpes zoster patients with peptic ulcer were at greater risk of postherpetic neuralgia. Adult zoster patients without postherpetic neuralgia and postherpetic neuralgia patients were automatically selected from a medical center's electronic database using herpes zoster/postherpetic neuralgia ICD-9 codes supported with inclusion and exclusion criteria. Consequently, medical record review was performed to validate the diagnostic codes and all pertaining data including peptic ulcer, Helicobacter pylori (H. pylori) infection and ulcerogenic medications. Because no standard pain intensity measurement exists, opioid usage was used as a proxy measurement for moderate to severe pain. In total, 410 zoster patients without postherpetic neuralgia and 115 postherpetic neuralgia patients were included. Multivariate logistic regressions identified 60 years of age and older, peptic ulcer and greater acute herpetic pain as independent predictors for postherpetic neuralgia. Among etiologies of peptic ulcer, H. pylori infection and usage of non-selective nonsteroidal anti-inflammatory drugs were significantly associated with the increased risk of postherpetic neuralgia; conversely, other etiologies were not significantly associated with the postherpetic neuralgia risk. In conclusion, 60 years of age and older, peptic ulcer and greater acute herpetic pain are independent predictors for postherpetic neuralgia in adult herpes zoster patients. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
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Modified effect of urinary cadmium on breast cancer risk by selenium.
Clin. Chim. Acta
PUBLISHED: 08-20-2014
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Previous experimental studies have shown an antagonistic interaction between cadmium and selenium. We explored the interaction between cadmium and selenium on human breast cancer risk.
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[Determination of inorganic elements in Antrodia camphorata powder by ICP-MS].
Zhong Yao Cai
PUBLISHED: 08-07-2014
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To establish a method for simultaneous analysis of 22 inorganic elements in Antrodia camphorata powder by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Additionally, inorganic elements of Ganoderma lucidum had been detected and compared.
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Thermo-responsive release of curcumin from micelles prepared by self-assembly of amphiphilic P(NIPAAm-co-DMAAm)-b-PLLA-b-P(NIPAAm-co-DMAAm) triblock copolymers.
Int J Pharm
PUBLISHED: 07-24-2014
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Thermo-responsive micelles are prepared by self-assembly of amphiphilic triblock copolymers composed of a poly(l-lactide) (PLLA) central block and two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) lateral blocks, using solvent evaporation/film hydration method. The resulting micelles exhibit very low critical micelle concentration (CMC) which slightly increases from 0.0113 to 0.0144mgmL(-1) while the DMAAm content increases from 31.8 to 39.4% in the hydrophilic P(NIPAAm-co-DMAAm) blocks. The lower critical solution temperatures (LCST) of copolymers varies from 44.7°C to 49.4°C in water as determined by UV spectroscopy, and decreases by ca. 3.5°C in phosphate buffered saline (PBS). Curcumin was encapsulated in the core of micelles. High drug loading up to 20% is obtained with high loading efficiency (>94%). The LCST of drug loaded micelles ranges from 37.5 to 38.0°C with drug loading increasing from 6.0 to 20%. The micelles with diameters ranging from 47.5 to 88.2nm remain stable over one month due to the negative surface charge as determined by zeta potential (-12.4 to -18.7mV). Drug release studies were performed under in vitro conditions at 37°C and 40°C, i.e. below and above the LCST, respectively. Initial burst release is observed in all cases, followed by a slower release. The release rate is higher at 40°C than that at 37°C due to thermo-responsive release across the LCST. On the other hand, micelles with lower drug loading exhibit higher release rate than those with higher drug loading, which is assigned to the solubility effect. Peppas' theory was applied to describe the release behaviors. Moreover, the in vitro cytotoxicity of copolymers was evaluated using MTT assay. The results show that the copolymers present good cytocompatibility. Therefore, the nano-scale size, low CMC, high drug loading and stability, as well as good biocompatibility indicate that these thermo-responsive triblock copolymer micelles present a good potential as carrier for targeted delivery of anticancer drugs.
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Association of Epstein-Barr virus and passive smoking with the risk of breast cancer among Chinese women.
Eur. J. Cancer Prev.
PUBLISHED: 07-11-2014
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Reactivation of Epstein-Barr virus (EBV), as indexed by the higher immunoglobulin A (IgA) antibody titers, was reported to be associated with an increased risk of breast cancer. Passive smoking plays a role in host immune responses and may modify the association of EBV with breast cancer. We carried out a case-control study using data from 349 incident breast cancer cases and 500 age-matched controls in the Guangzhou Breast Cancer Study to investigate the interactions of EBV antibodies and passive smoking on breast cancer risk. A higher risk of breast cancer was observed in passive smokers who were seropositive for EBV viral capsid antigen IgA or nuclear antigen-1 IgA in serum compared with those with the seronegativity and no passive smoking [odds ratio 3.13 (95% confidence interval, 1.76-5.56)]. There was a significant linear trend for the risk of breast cancer from IgA seropositivity with passive smoking, only IgA seropositivity, only passive smoking, to seronegativity without passive smoking (P<0.001), but the interaction in either multiplicative or additive models was not significant. No significant association was found between passive smoking and EBV IgA seropositivity. The present study confirmed the associations of EBV IgA antibodies and passive smoking with the risk of breast cancer and suggested that there was no synergic action between passive smoking and EBV IgA seropositivity on the risk of breast cancer.
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ARRB1/?-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia.
Autophagy
PUBLISHED: 06-25-2014
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Autophagy, a highly conserved process conferring cytoprotection against stress, contributes to the progression of cerebral ischemia. ?-arrestins are multifunctional proteins that mediate receptor desensitization and serve as important signaling scaffolds involved in numerous physiopathological processes. Here, we show that both ARRB1 (arrestin, ? 1) and ARRB2 (arrestin, ? 2) were upregulated by cerebral ischemic stress. Knockout of Arrb1, but not Arrb2, aggravated the mortality, brain infarction, and neurological deficit in a mouse model of cerebral ischemia. Accordingly, Arrb1-deficient neurons exhibited enhanced cell injury upon oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Deletion of Arrb1 did not affect the cerebral ischemia-induced inflammation, oxidative stress, and nicotinamide phosphoribosyltransferase upregulation, but markedly suppressed autophagy and induced neuronal apoptosis/necrosis in vivo and in vitro. Additionally, we found that ARRB1 interacted with BECN1/Beclin 1 and PIK3C3/Vps34, 2 major components of the BECN1 autophagic core complex, under the OGD condition but not normal conditions in neurons. Finally, deletion of Arrb1 impaired the interaction between BECN1 and PIK3C3, which is a critical event for autophagosome formation upon ischemic stress, and markedly reduced the kinase activity of PIK3C3. These findings reveal a neuroprotective role for ARRB1, in the context of cerebral ischemia, centered on the regulation of BECN1-dependent autophagosome formation.
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Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk.
Cancer Epidemiol
PUBLISHED: 06-13-2014
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Physical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk.
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IL-17A promotes ventricular remodeling after myocardial infarction.
J. Mol. Med.
PUBLISHED: 05-23-2014
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Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We previously demonstrated that interleukin (IL)-17A plays a pathogenic role in myocardial ischemia/reperfusion injury and viral myocarditis. However, the role of IL-17A in post-MI remodeling and the related mechanisms have not been fully elucidated. Acute MI was induced by permanent ligation of the left anterior descending coronary artery in C57BL/6 mice. Repletion of IL-17A significantly aggravated both early- and late-phase ventricular remodeling, as demonstrated by increased infarct size, deteriorated cardiac function, increased myocardial fibrosis, and cardiomyocyte apoptosis. By contrast, genetic IL-17A deficiency had the opposite effect. Additional studies in vitro indicated that IL-17A induces neonatal cardiomyocyte (from C57BL/6 mice) apoptosis through the activation of p38, p53 phosphorylation, and Bax redistribution. These data demonstrate that IL-17A induces cardiomyocyte apoptosis through the p38 mitogen-activated protein kinase (MAPK)-p53-Bax signaling pathway and promotes both early- and late-phase post-MI ventricular remodeling. IL-17A might be an important target in preventing heart failure after MI.
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Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 05-16-2014
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The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation. It has been reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats, whereas angiotensin-converting enzyme 2 (ACE2) in the brain has been suggested to be beneficial to hypertension. This study was designed to determine the effect of ACE2 gene transfer into the RVLM on tonically active glutamatergic input in spontaneously hypertensive rats (SHRs). Lentiviral particles containing enhanced green fluorescent protein (lenti-GFP) or ACE2 (lenti-ACE2) were injected bilaterally into the RVLM. Both protein expression and activity of ACE2 in the RVLM were increased in SHRs after overexpression of ACE2. A significant reduction in blood pressure and heart rate in SHRs was observed 6 wk after lenti-ACE2 injected into the RVLM. The concentration of glutamate in microdialysis fluid from the RVLM was significantly reduced by an average of 61% in SHRs with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity evoked by bilateral injection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nl) into the RVLM in SHRs. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in SHRs, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension.
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Arterial baroreflex dysfunction impairs ischemia-induced angiogenesis.
J Am Heart Assoc
PUBLISHED: 05-14-2014
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Endothelium-derived acetylcholine (eACh) plays an important role in the regulation of vascular actions in response to hypoxia, whereas arterial baroreflex (ABR) dysfunction impairs the eACh system. We investigated the effects of ABR dysfunction on ischemia-induced angiogenesis in animal models of hindlimb ischemia with a special focus on eACh/nicotinic ACh receptor (nAChR) signaling activation.
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Effect of oridonin-mediated hallmark changes on inflammatory pathways in human pancreatic cancer (BxPC-3) cells.
World J. Gastroenterol.
PUBLISHED: 05-02-2014
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To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells.
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Application of the triage assessment system for psychological assessment for pregnant women with a deadly fetal abnormality.
Int J Nurs Pract
PUBLISHED: 04-25-2014
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To explore suitable scales to assess psychological status of pregnant women whose fetuses have grave deformities, a face-to-face interview guided by the Triage Assessment System (TAS) was conducted. Also, a questionnaire of the Impact of Event Scale-Revised (IES-R) was obtained in 44 pregnant women diagnosed with a fetal deformity. Percentages and non-parametric Spearman correlations were used to analyse the scores of the two scales. The total score of TAS ranged from 3 to 26, with a mean of 9.93; and the total score of IES-R ranged from 5 to 63, with a mean of 40.36. The total score and the two subscales of each scale were significantly correlated (P?
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Quantitative determination and validation of avermectin B1a in commercial products using quantitative nuclear magnetic resonance spectroscopy.
Magn Reson Chem
PUBLISHED: 03-14-2014
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Nuclear magnetic resonance is defined as a quantitative spectroscopic tool that enables a precise determination of the number of substances in liquids as well as in solids. There is few report demonstrating the application of NMR in the quantification of avermectin B1a (AVB1a ); here, a proton nuclear magnetic resonance spectroscopy ((1) H NMR) using benzene [1-methoxy-4-(2-nitroethyl) (PMN)] as an internal standard and deuterochloroform as an NMR solvent was tested for the quantitative determination of AVB1a . The integrated signal of AVB1a at 5.56?ppm and the signal of PMN at 8.14?ppm in the (1) H NMR spectrum were used for quantification purposes. Parameters of specificity, linearity, accuracy, precision, intermediate precision, range, limit of detection (LOD), limit of quantification (LOQ), stability and robustness were validated. The established method was accurate and precise with good recovery (98.86%) and relative standard deviation (RSD) of assay (0.34%) within the linearity of the calibration curve ranging from 5.08 to 13.58?mg/ml (R(2) ?=?0.9999). The LOD and LOQ were 0.009 and 0.029?mg/ml, which indicated the excellent sensitivity of the method. The stability of the method was testified by a calculated RSD of 0.11%. The robustness was testified by modification of four different parameters, and the differences among each parameter were all less than 0.1%. Comparing with the assay described by the manufacturer of avermectin tablets, there was no significant difference between the assay obtained by HPLC and quantitative NMR (qNMR), which indicated qNMR was a simple and efficient method for the determination of AVB1a in commercial formulation products.
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Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.
Biomed Res Int
PUBLISHED: 03-12-2014
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Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.
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HER2-enriched tumors have the highest risk of local recurrence in Chinese patients treated with breast conservation therapy.
Asian Pac. J. Cancer Prev.
PUBLISHED: 02-18-2014
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The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women.
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Predictors of memory and processing speed dysfunctions after traumatic brain injury.
Biomed Res Int
PUBLISHED: 02-07-2014
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The aims of this study were to evaluate the predictive value of admission Glasgow Coma Scale (GCS) scores, duration of unconsciousness, neurosurgical intervention, and countercoup lesion on the impairment of memory and processing speed functions six months after a traumatic brain injury (TBI) based on a structural equation modeling.
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Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells.
Sci Rep
PUBLISHED: 02-06-2014
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PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.
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Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.
Head Neck
PUBLISHED: 02-04-2014
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Background: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. Methods: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cell and anti-apoptosis was performed. Results: Long-term NNK exposure dose-dependently enhances migration and invasion with morphological alterations. Furthermore, NNK exposure also up-regulates snail, promotes sphere-forming ability and overexpresses ALDH1, Nanog, OCT4, ABCG2 and MDR1. Conclusions: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that ?7-nAChR inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC. Head Neck, 2014.
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Lack of efficacy of motor cortex stimulation for the treatment of neuropathic pain in 14 patients.
Neuromodulation
PUBLISHED: 01-22-2014
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Motor cortex stimulation has been reported as an effective treatment for medically resistant neuropathic pain. The goal of this study is to review the efficacy of this treatment in a series of 14 patients.
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Expression of cannabinoid receptor 2 and its inhibitory effects on synovial fibroblasts in rheumatoid arthritis.
Rheumatology (Oxford)
PUBLISHED: 01-17-2014
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Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which shows no psychoactivity. However, it is still unclear whether CB2R is expressed in fibroblast-like synoviocytes (FLS) of RA. In this study we investigated whether CB2R is expressed in FLS of RA, and whether CB2R activation modulates the function of RA-FLS.
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Mobile robot self-localization system using single webcam distance measurement technology in indoor environments.
Sensors (Basel)
PUBLISHED: 01-13-2014
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A single-webcam distance measurement technique for indoor robot localization is proposed in this paper. The proposed localization technique uses webcams that are available in an existing surveillance environment. The developed image-based distance measurement system (IBDMS) and parallel lines distance measurement system (PLDMS) have two merits. Firstly, only one webcam is required for estimating the distance. Secondly, the set-up of IBDMS and PLDMS is easy, which only one known-dimension rectangle pattern is needed, i.e., a ground tile. Some common and simple image processing techniques, i.e., background subtraction are used to capture the robot in real time. Thus, for the purposes of indoor robot localization, the proposed method does not need to use expensive high-resolution webcams and complicated pattern recognition methods but just few simple estimating formulas. From the experimental results, the proposed robot localization method is reliable and effective in an indoor environment.
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Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Yukinori Okada, Di Wu, Gosia Trynka, Towfique Raj, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Shinji Yoshida, Robert R Graham, Arun Manoharan, Ward Ortmann, Tushar Bhangale, Joshua C Denny, Robert J Carroll, Anne E Eyler, Jeffrey D Greenberg, Joel M Kremer, Dimitrios A Pappas, Lei Jiang, Jian Yin, Lingying Ye, Ding-Feng Su, Jian Yang, Gang Xie, Ed Keystone, Harm-Jan Westra, Tonu Esko, Andres Metspalu, Xuezhong Zhou, Namrata Gupta, Daniel Mirel, Eli A Stahl, Dorothée Diogo, Jing Cui, Katherine Liao, Michael H Guo, Keiko Myouzen, Takahisa Kawaguchi, Marieke J H Coenen, Piet L C M van Riel, Mart A F J van de Laar, Henk-Jan Guchelaar, Tom W J Huizinga, Philippe Dieudé, Xavier Mariette, S Louis Bridges, Alexandra Zhernakova, René E M Toes, Paul P Tak, Corinne Miceli-Richard, So-Young Bang, Hye-Soon Lee, Javier Martín, Miguel A González-Gay, Luis Rodriguez-Rodriguez, Solbritt Rantapää-Dahlqvist, Lisbeth Arlestig, Hyon K Choi, Yoichiro Kamatani, Pilar Galán, Mark Lathrop, , Steve Eyre, John Bowes, Anne Barton, Niek de Vries, Larry W Moreland, Lindsey A Criswell, Elizabeth W Karlson, Atsuo Taniguchi, Ryo Yamada, Michiaki Kubo, Jun S Liu, Sang-Cheol Bae, Jane Worthington, Leonid Padyukov, Lars Klareskog, Peter K Gregersen, Soumya Raychaudhuri, Barbara E Stranger, Philip L De Jager, Lude Franke, Peter M Visscher, Matthew A Brown, Hisashi Yamanaka, Tsuneyo Mimori, Atsushi Takahashi, Huji Xu, Timothy W Behrens, Katherine A Siminovitch, Shigeki Momohara, Fumihiko Matsuda, Kazuhiko Yamamoto, Robert M Plenge.
Nature
PUBLISHED: 01-07-2014
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A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ?10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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CXCR6 deficiency attenuates pressure overload-induced monocytes migration and cardiac fibrosis through downregulating TNF-?-dependent MMP9 pathway.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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An immerging role of TNF-? in collagen synthesis and cardiac fibrosis implies the significance of TNF-? production in the development of myocardial remodeling. Our previous study showed a reduction of TNF-? and attenuated cardiac remodeling in CXCR6 knockout (KO) mice after ischemia/reperfusion injury. However, the potential mechanism of TNF-?-mediated cardiac fibrosis with pressure overload has not been well elucidated. In the present study, we aim to investigate the role of CXCR6 in TNF-? release and myocardial remodeling in response to pressure overload. Pressure overload was performed by constriction of transverse aorta (TAC) surgery on CXCR6 KO mice and C57 wild-type (WT) counterparts. At 6 weeks after TAC, cardiac remodeling was assessed by echocardiography, cardiac TNF-? release and its type I receptor (TNFRI), were detected by ELISA and western blot, collagen genes Col1a1 (type I) and Col3a1 (type III) were examined by real-time PCR. Compared with CXCR6 WT mice, CXCR6 KO mice exhibited less cardiac dysfunction, reduced expression of TNFRI, Col1a1 and Col3a. In vitro, we confirmed that CXCR6 deficiency led to reduced homing and infiltration of CD11b(+) monocytes, which contributed to attenuated TNF-? release in myocardium. Furthermore, TNFRI antagonist pretreatment blocked AT1 receptor signaling and NOX4 expression, reduced collagen synthesis, and blunted the activity of MMP9 in CXCR6 WT mice after TAC, but these were not observed in CXCR6 KO mice. In the present work, we propose a mechanism that CXCR6 is essential for pressure overload-mediated myocardial recruitment of monocytes, which contributes to cardiac fibrosis through TNF-?-dependent MMP9 activation and collagen synthesis.
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Generation of mastitis resistance in cows by targeting human lysozyme gene to ?-casein locus using zinc-finger nucleases.
Proc. Biol. Sci.
PUBLISHED: 01-01-2014
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Mastitis costs the dairy industry billions of dollars annually and is the most consequential disease of dairy cattle. Transgenic cows secreting an antimicrobial peptide demonstrated resistance to mastitis. The combination of somatic cell gene targeting and nuclear transfer provides a powerful method to produce transgenic animals. Recent studies found that a precisely placed double-strand break induced by engineered zinc-finger nucleases (ZFNs) stimulated the integration of exogenous DNA stretches into a pre-determined genomic location, resulting in high-efficiency site-specific gene addition. Here, we used ZFNs to target human lysozyme (hLYZ) gene to bovine ?-casein locus, resulting in hLYZ knock-in of approximately 1% of ZFN-treated bovine fetal fibroblasts (BFFs). Gene-targeted fibroblast cell clones were screened by junction PCR amplification and Southern blot analysis. Gene-targeted BFFs were used in somatic cell nuclear transfer. In vitro assays demonstrated that the milk secreted by transgenic cows had the ability to kill Staphylococcus aureus. We report the production of cloned cows carrying human lysozyme gene knock-in ?-casein locus using ZFNs. Our findings open a unique avenue for the creation of transgenic cows from genetic engineering by providing a viable tool for enhancing resistance to disease and improving the health and welfare of livestock.
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The application of quantitative NMR for the facile, rapid and reliable determination of clindamycin phosphate in a conventional tablet formulation.
Magn Reson Chem
PUBLISHED: 01-01-2014
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Spectroscopic tools such as NMR can be applied to the quantitative analysis of active pharmaceutical ingredients with relative ease and accuracy. Here, we demonstrate the quantification of clindamycin phosphate (CLP) in a conventional tablet formulation, performed using potassium hydrogen phthalate (KHP) as the internal standard and deuterium oxide (D2O) as the NMR solvent. The methyl protons signal of CLP at 0.72 ppm (triplet) relative to the signal of KHP at 7.37-7.40 ppm (multiplet) was used for quantification purposes using (1)H NMR. This method was shown to be specific and linear (r = 0.9997) within the CLP concentration range from 7.2 to 23.1 mg per 0.5 ml of D2O. The maximum relative standard deviation (RSD) of accuracy and precision was calculated at 0.39% and 0.64%, respectively. The limits of detection (LOD) and quantification were 0.04 and 0.11 mg/ml, respectively. The method was highly stable with a calculated RSD of 0.03%. The robustness of the method was demonstrated by changing four different parameters, and the difference among each parameter was ? 0.78%. The findings of this work were in good agreement with previously reported conventional HPLC-based approaches, highlighting its applicability in the determination of other active pharmaceutical ingredients in conventional formulations for quality control purposes.
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[Association between urinary cadmium and clinicopathological characteristics of breast cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-10-2013
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The aim of this study was to investigate the association between urinary cadmium and clinicopathological characteristics of breast cancer.
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Effects of modified biliopancreatic diversion on glucose tolerance of GK rats.
Obes Surg
PUBLISHED: 10-31-2013
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The purpose of this study was to investigate the hypoglycemic effect of new biliopancreatic diversion and duodenal-jejunal bypass in Goto-Kakizaki rats and observe effects of the new surgical procedure on the glucose tolerance of GK rats.
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Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid.
J. Lipid Res.
PUBLISHED: 10-01-2013
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We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR?/?) mice fed a Western diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in the small intestine of LDLR?/? mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by quantitative RT-PCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i) levels of LPA in the small intestine were similar to those induced by feeding WD; ii) gene expression changes in the small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL-cholesterol levels, and the fast-performance liquid chromatography lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes. We conclude that: i) WD-mediated systemic inflammation and dyslipidemia may be in part due to WD-induced increases in small intestine LPA levels; and ii) Tg6F reduces WD-mediated systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA levels in the small intestine.
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Enhanced ozonation degradation of di-n-butyl phthalate by zero-valent zinc in aqueous solution: Performance and mechanism.
J. Hazard. Mater.
PUBLISHED: 09-13-2013
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Enhanced ozonation degradation of di-n-butyl phthalate (DBP) by zero-valent zinc (ZVZ) has been investigated using a semi-continuous reactor in aqueous solution. The results indicated that the combination of ozone (O3) and ZVZ showed an obvious synergetic effect, i.e. an improvement of 54.8% on DBP degradation was obtained by the O3/ZVZ process after 10min reaction compared to the cumulative effect of O3 alone and O2/ZVZ. The degradation efficiency of DBP increased gradually with the increase of ZVZ dosage, enhanced as solution pH increasing from 2.0 to 10.0, and more amount of DBP was degraded with the initial concentration of DBP arising from 0.5 to 2.0mgL(-1). Recycling use of ZVZ resulted in the enhancement of DBP degradation, because the newly formed zinc oxide took part in the reaction. The mechanism investigation demonstrated that the enhancement effect was attributed to the introduction of ZVZ, which could promote the utilization of O3, enhance the formation of superoxide radical by reducing O2 via one-electron transfer, accelerate the production of hydrogen peroxide and the generation of hydroxyl radical. Additionally, the newly formed zinc oxide on ZVZ surface also contributed to the enhancement of DBP degradation in the recycling use of ZVZ. Most importantly, the O3/ZVZ process was also effective in enhanced ozonation degradation of DBP under the background of actual waters.
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The protective action of ketanserin against lipopolysaccharide-induced shock in mice is mediated by inhibiting inducible NO synthase expression via the MEK/ERK pathway.
Free Radic. Biol. Med.
PUBLISHED: 07-26-2013
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Nitric oxide (NO) plays an important role in the pathogenesis of endotoxic shock. This work tested the hypothesis that ketanserin could attenuate endotoxic shock by inhibiting the expression of inducible NO synthase (iNOS). The results demonstrated that ketanserin could inhibit iNOS expression in the heart, lungs, liver, and kidneys and nitrate production in the serum upon endotoxic shock in mice. In RAW264.7 cells, ketanserin significantly inhibited the expression of iNOS and decreased the production of NO, TNF?, IL-6, and reactive oxygen species upon lipopolysaccharide (LPS) challenge. Ketanserin also increased the level of ATP and mitochondrial membrane potential in RAW264.7 cells upon LPS exposure. LPS-induced iNOS expression was inhibited by the 5-HT2A receptor antagonist ritanserin and not the ?1 receptor antagonist prazosin. Knockdown of 5-HT2A receptor by siRNA abolished the inhibitory effect of ketanserin on the expression of iNOS. These results indicated that the inhibitory effect of ketanserin on the expression of iNOS is mediated by blocking the 5-HT2A receptor. Furthermore, ketanserin significantly inhibited the activation of ERK1/2 and NF-?B signal. Pretreatment with PD184352, a specific inhibitor of ERK1/2, blocked the inhibitory effect of ketanserin on the expression of iNOS and NO production, indicating a critical role for the MEK/ERK1/2 signaling pathway. Collectively, our findings indicate that inhibition of the expression of iNOS via the MEK/ERK pathway mediates the protective effects of ketanserin against LPS-induced shock in mice.
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Ketanserin improves cardiac performance after myocardial infarction in spontaneously hypertensive rats partially through restoration of baroreflex function.
Acta Pharmacol. Sin.
PUBLISHED: 07-23-2013
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Aim:Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction (MI). Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved.Methods:Spontaneously hypertensive rats (SHR) were treated with ketanserin (0.3 mg·kg(-1)·d(-1)). Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter (VAChT) and ?7 nicotinic acetylcholine receptor (?7-nAChR) in ischemic myocardium, angiogenesis, cardiac function, and left ventricular (LV) remodeling were evaluated subsequently.Results:Ketanserin significantly improved baroreflex sensitivity (0.62±0.21 vs 0.34±0.12 ms/mmHg, P<0.01) and vagal tonic activity (heart rate changes in response to atropine, 54.8±16.2 vs 37.6±13.4 bpm, P<0.01) without affecting the blood pressure or basic heart rate in SHR. Treatment of SHR with ketanserin prominently improved cardiac function and alleviated LV remodeling, as reflected by increases in the ejection fraction, fractional shortening, and LV systolic pressure as well as decreases in LV internal diameter and LV relative weight. The capillary density, vascular endothelial growth factor expression, and blood flow in the ischemic myocardium were significantly higher in the ketanserin-treated group. In addition, ketanserin markedly increased the expression of VAChT and ?7-nAChR in ischemic myocardium.Conclusion:Ketanserin improved post-MI cardiac function and angiogenesis in ischemic myocardium. The findings provide a mechanistic basis for restoring baroreflex function using ketanserin in the treatment of MI.
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Clinical application of mucosal valve technique for anastomosis during esophagogastrostomy.
J. Gastrointest. Surg.
PUBLISHED: 07-20-2013
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The study aims to compare the efficacy in prevention of anastomotic complications using layer-to-layer mucosal valve technique versus circular stapled technique for esophagogastric intrathoracic anastomosis after resection for esophageal and gastric cardiac carcinoma.
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Lipopolysaccharide neutralization by a novel peptide derived from phosvitin.
Int. J. Biochem. Cell Biol.
PUBLISHED: 05-29-2013
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Lipopolysaccharide (LPS), also known as endotoxin, is the primary trigger of sepsis, which is associated with high mortality in patients. No therapeutic agents are currently efficacious enough to protect patients from sepsis characterized by LPS-mediated tissue damage and organ failure. Previously, a phosvitin-derived peptide, Pt5, which consists of the C-terminal 55 residues of zebrafish phosvitin, has been shown to function as an antibacterial agent. In this study, we have generated six mutants by site-directed mutagenesis based on the sequence of Pt5, and found that one of the six mutants, Pt5e, showed the strongest bactericidal activities against Escherichia coli and Staphylococcus aureus. We then demonstrated that Pt5e was able to bind to LPS and lipoteichoic acid (LTA). More importantly, we showed that Pt5e significantly inhibited LPS-induced tumor-necrosis factor (TNF)-? and interleukin (IL)-1? release from murine RAW264.7 cells and considerably reduced serum TNF-? and IL-1? levels in mice. Additionally, Pt5e protected the liver from damage by LPS, and remarkably promoted the survival rate of the endotoxemia mice. Furthermore, Pt5e displayed no cytotoxicity to murine RAW264.7 macrophages and no hemolytic activity toward human red blood cells. These data together indicate that Pt5e is an endotoxin-neutralizing agent with a therapeutic potential in clinical treatment of LPS-induced sepsis.
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Intraoperative intracranial pressure and cerebral perfusion pressure for predicting surgical outcome in severe traumatic brain injury.
Kaohsiung J. Med. Sci.
PUBLISHED: 05-28-2013
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Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated for use as prognostic indicators after surgery for severe traumatic brain injury (TBI), and threshold ICP and CPP values were determined to provide guidelines for patient management. This retrospective study reviewed data for 66 patients (20 females and 46 males) aged 13-83 years (average age, 48 years) who had received decompressive craniectomy and hematoma evacuation for severe TBI. The analysis of clinical characteristics included Glascow Coma Scale score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma thickness observed on computed tomography scan, Glasgow Outcome Scale score, and mortality. Patients whose treatment included ICP monitoring had significantly better prognosis (p < 0.001) and significantly lower mortality (p = 0.016) compared to those who did not receive ICP monitoring. At all three major steps of the procedure, i.e., creation of the burr hole, evacuation of the hematoma, and closing of the wound, intraoperative ICP and CPP values significantly differed. The ICP and CPP values were also significantly associated with surgical outcome in the severe TBI patients. Between hematoma evacuation and wound closure, ICP and CPP values differed by 6.8 ± 4.5 and 6.5 ± 4.6 mmHg, respectively (mean difference, 6 mmHg). Intraoperative thresholds were 14 mmHg for ICP and 56mmH for CPP. Monitoring ICP and CPP during surgery improves management of severe TBI patients and provides an early prognostic indicator. During surgery for severe TBI, early detection of increased ICP is also crucial for enabling sufficiently early treatment to improve surgical outcome. However, further study is needed to determine the optimal intraoperative ICP and CPP thresholds before their use as subjective guidelines for managing severe TBI patients.
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CYP19A1 gene polymorphisms and risk of lung cancer.
J. Int. Med. Res.
PUBLISHED: 05-13-2013
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To investigate the association between polymorphisms of aromatase (encoded by the CYP19A1 gene and a key enzyme in biosynthesis of oestradiol) and the risk of lung cancer, and whether there were differences stratified by sex and smoking history.
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Reciprocal relationship of Tn/NF-?B and sTn as an indicator of the prognosis of oral squamous cell carcinoma.
Histopathology
PUBLISHED: 05-10-2013
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In order to determine whether the expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-?B (NF-?B), is associated with the invasiveness of oral squamous cell carcinoma (OSCC), this study has attempted to investigate the correlation of the aforementioned markers with the well-established invasive pattern grading score (IPGS) and clinicopathological parameters.
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MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines.
Cell Res.
PUBLISHED: 04-06-2013
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The vagus nerve can control inflammatory response through a cholinergic anti-inflammatory pathway, which is mediated by the ?7-nicotinic acetylcholine receptor (?7nAChR) on macrophages. However, the intracellular mechanisms that link ?7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-? converting enzyme (TACE) to reduce TNF-? release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.
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Synthesis and structure-activity relationship of 8-substituted protoberberine derivatives as a novel class of antitubercular agents.
Chem Cent J
PUBLISHED: 04-01-2013
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The emergence of multi-drug resistant tuberculosis (MDR-TB) has heightened the need for new chemical classes and innovative strategies to tackle TB infections. It is urgent to discover new classes of molecules without cross-resistance with currently used antimycobacterial drugs.
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The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma.
J. Pathol.
PUBLISHED: 03-20-2013
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Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.
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Effects of granulosa cells on steroidogenesis, proliferation and apoptosis of stromal cells and theca cells derived from the goat ovary.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 03-07-2013
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The aim of this study was to investigate the effect of granulosa cells from small antral follicles on steroidogenesis, proliferation and apoptosis of goat ovarian stromal and theca cells in vitro. Using Transwell co-culture system, we evaluated androgen production, LH responsiveness, cell proliferation and apoptosis and some molecular expression regarding steroidogenic enzyme and apoptosis-related genes in stromal and theca cells. The results indicated that the co-culture with granulosa cells increased steroidogenesis, LH responsiveness and bcl-2 gene expression as well as decreased apoptotic bax and bad expressions in stromal and theca cells. Thus, granulosa cells had a capacity of promoting steroidogenesis in stromal cell and LH responsiveness in cortical stromal cells, maintaining steroidogenesis in theca cells, inhibiting apoptosis of cortical stromal cells and improving anti-apoptotic abilities of stromal and theca cells.
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Cannabinoid receptor 2 protects against acute experimental sepsis in mice.
Mediators Inflamm.
PUBLISHED: 03-04-2013
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The systemic inflammatory response syndrome can be self-limited or can progress to severe sepsis and septic shock. Despite significant advances in the understanding of the molecular and cellular mechanisms of septic shock, it is still one of the most frequent and serious problems confronting clinicians in the treatments. And the effects of cannabinoid receptor 2 (CB2R) on the sepsis still remain undefined. The present study was aimed to explore the role and mechanism of CB2R in acute sepsis model of mice. Here, we found that mice were more vulnerable for lipopolysaccharide- (LPS-) induced death and inflammation after CB2R deletion (CB2R(-/-)). CB2R agonist, GW405833, could significantly extend the survival rate and decrease serum proinflammatory cytokines in LPS-treated mice. GW405833 dose-dependently inhibits proinflammatory cytokines release in splenocytes and peritoneal macrophages as well as splenocytes proliferation, and these effects were partly abolished in CB2R(-/-) splenocytes but completely abolished in CB2R(-/-) peritoneal macrophages. Further studies showed that GW405833 inhibits LPS-induced phosphorylation of ERK1/2 and STAT3 and blocks I ? B ? degradation and NF- ?B p65 nuclear translocation in macrophages. All data together showed that CB2R provides a protection and is a potential therapeutic target for the sepsis.
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Involvement of arterial baroreflex in the protective effect of dietary restriction against stroke.
J. Cereb. Blood Flow Metab.
PUBLISHED: 02-27-2013
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Dietary restriction (DR) protects against neuronal dysfunction and degeneration, and reduces the risk of ischemic stroke. This study examined the role of silent information regulator T1 (SIRT1) and arterial baroreflex in the beneficial effects of DR against stroke, using two distinct stroke models: stroke-prone spontaneously hypertensive rats (SP-SHRs) and Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Sirt1 knockout (KO) mice were used to examine the involvement of sirt1. Sinoaortic denervation was used to inactivate arterial baroreflex. Dietary restriction was defined as 40% reduction of dietary intake. Briefly, DR prolonged the life span of SP-SHRs and reduced the infarct size induced by MCAO. Dietary restriction also improved the function arterial baroreflex, decreased the release of proinflammatory cytokines, and reduced end-organ damage. The beneficial effect of DR on stroke was markedly attenuated by blunting arterial baroreflex. Lastly, the infarct area in sirt1 KO mice was significantly larger than in the wild-type mice. However, the beneficial effect of DR against ischemic injury was still apparent in sirt1 KO mice. Accordingly, arterial baroreflex, but not sirt1, is important in the protective effect of DR against stroke.
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ALDH2 protects against stroke by clearing 4-HNE.
Cell Res.
PUBLISHED: 02-05-2013
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Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Using an unbiased proteomic search, we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR). We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2 conferred neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKC?. Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE, and to protect against ischemic cerebral injury through the PKC?-ALDH2 pathway. In SHR-SP, serum 4-HNE level was persistently elevated and correlated inversely with the lifespan. The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke. These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects, and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.
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A novel approach to oral apoA-I mimetic therapy.
J. Lipid Res.
PUBLISHED: 02-02-2013
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Transgenic tomato plants were constructed with an empty vector (EV) or a vector expressing an apoA-I mimetic peptide, 6F. EV or 6F tomatoes were harvested, lyophilized, ground into powder, added to Western diet (WD) at 2.2% by weight, and fed to LDL receptor-null (LDLR(-/-)) mice at 45 mg/kg/day 6F. After 13 weeks, the percent of the aorta with lesions was 4.1 ± 4%, 3.3 ± 2.4%, and 1.9 ± 1.4% for WD, WD + EV, and WD + 6F, respectively (WD + 6F vs. WD, P = 0.0134; WD + 6F vs. WD + EV, P = 0.0386; WD + EV vs. WD, not significant). While body weight did not differ, plasma serum amyloid A (SAA), total cholesterol, triglycerides, and lysophosphatidic acid (LPA) levels were less in WD + 6F mice; P < 0.0295. HDL cholesterol and paroxonase-1 activity (PON) were higher in WD + 6F mice (P = 0.0055 and P = 0.0254, respectively), but not in WD + EV mice. Plasma SAA, total cholesterol, triglycerides, LPA, and 15-hydroxyeicosatetraenoic acid (HETE) levels positively correlated with lesions (P < 0.0001); HDL cholesterol and PON were inversely correlated (P < 0.0001). After feeding WD + 6F: i) intact 6F was detected in small intestine (but not in plasma); ii) small intestine LPA was decreased compared with WD + EV (P < 0.0469); and iii) small intestine LPA 18:2 positively correlated with the percent of the aorta with lesions (P < 0.0179). These data suggest that 6F acts in the small intestine and provides a novel approach to oral apoA-I mimetic therapy.
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Reappraisal of the anticancer efficacy of quercetin in oral cancer cells.
J Chin Med Assoc
PUBLISHED: 01-24-2013
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Despite increased experience in therapy, the overall outcome of oral squamous cell carcinoma (OSCC) has not improved because of the relative resistance to chemotherapeutic drugs in addition to local invasion and frequent regional lymph node metastases. Quercetin (Qu) is a principal flavonoid compound and an excellent free-radical-scavenging antioxidant that promotes apoptosis. Limited reports regarding the molecular or cellular role of Qu in anticancer properties on OSCC have been presented. This study was conducted to clarify the efficacy of Qu on OSCC in vitro and further to evaluate the possible mechanism(s).
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GeneSearch™ BLN Assay could replace frozen section and touch imprint cytology for intra-operative assessment of breast sentinel lymph nodes.
Breast Cancer
PUBLISHED: 01-16-2013
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BACKGROUND: Breast cancer sentinel lymph node (SLN) biopsy has become a common procedure. The GeneSearch™ Breast Lymph Node Assay is a real-time reverse-transcriptase polymerase chain reaction assay for detecting nodal metastases larger than 0.2 mm. The trial is a prospective multi-center clinical trial conducted to validate the assay in China. METHODS: Four hundred and seventy-nine consecutive prospective patients were enrolled from six centers. SLNs were sectioned along the short axis into multiple blocks. Odd blocks were tested by the assay intra-operatively, and even blocks were assessed by post-operative histology. Six 4- to 6-?m-thick sections were taken every 150 ?m per block. In addition, intra-operative histological assessments were performed on the even blocks of 214 patients by frozen section (FS) and all blocks of 156 patients by touch imprint cytology (TIC). RESULTS: A total of 1046 SLNs were excised. Overall performance of the assay compared to post-operative histology was accuracy of 91.4 %, sensitivity of 87.5 %, and specificity of 92.9 %. There were no significant differences in assay performance of each center. After a learning curve of about 10 cases, the assay could be performed in a median time of about 35 min. The sensitivity of the assay was similar to the FS (84.9 %, P = 0.885) and was significantly higher than the TIC (70.0 %, P = 0.007) while the specificity of all were comparable. CONCLUSION: The GeneSearch™ Breast Lymph Node Assay is an accurate and rapid intra-operative assay for breast SLNs and it can replace FS and TIC for application.
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Effects of passive smoking on breast cancer risk in pre/post-menopausal women as modified by polymorphisms of PARP1 and ESR1.
Gene
PUBLISHED: 01-15-2013
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The association between passive smoking and breast cancer risk differs in pre- and post-menopausal women. We aimed to explore the modification effects of PARP1 rs1136410 and ESR1 rs2234693 on the association between passive smoking and breast cancer risk among pre- and post-menopausal women.
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17?-Estradiol attenuates secondary injury through activation of Akt signaling via estrogen receptor alpha in rat brain following subarachnoid hemorrhage.
J. Surg. Res.
PUBLISHED: 01-12-2013
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Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17?-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-? (ER-?) in rats.
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Establishment and Evaluation of a Stable Cattle Type II Alveolar Epithelial Cell Line.
PLoS ONE
PUBLISHED: 01-01-2013
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Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs) also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells) by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II) that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-? and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.
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A site-specific recombinase-based method to produce antibiotic selectable marker free transgenic cattle.
PLoS ONE
PUBLISHED: 01-01-2013
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Antibiotic selectable marker genes have been widely used to generate transgenic animals. Once transgenic animals have been obtained, the selectable marker is no longer necessary but raises public concerns regarding biological safety. The aim of this study was to prepare competent antibiotic selectable marker free transgenic cells for somatic cell nuclear transfer (SCNT). PhiC31 intergrase was used to insert a transgene cassette into a "safe harbor" in the bovine genome. Then, Cre recombinase was employed to excise the selectable marker under the monitoring of a fluorescent double reporter. By visually tracking the phenotypic switch from red to green fluorescence, antibiotic selectable marker free cells were easily detected and sorted by fluorescence-activated cell sorting. For safety, we used phiC31 mRNA and cell-permeant Cre protein in this study. When used as donor nuclei for SCNT, these safe harbor integrated marker-free transgenic cells supported a similar developmental competence of SCNT embryos compared with that of non-transgenic cells. After embryo transfer, antibiotic selectable marker free transgenic cattle were generated and anti-bacterial recombinant human ?-defensin-3 in milk was detected during their lactation period. Thus, this approach offers a rapid and safe alternative to produce antibiotic selectable marker free transgenic farm animals, thereby making it a valuable tool to promote the healthy development and welfare of transgenic farm animals.
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Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade.
PLoS ONE
PUBLISHED: 01-01-2013
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Metastasis occurs in a series of discrete steps involving invasion, angiogenesis, lymphovascular space permeation, and establishment of secondary tumors. Malignant pleural effusion (MPE), a type of tumor metastasis, is usually a poor prognostic sign for patients with pulmonary adenocarcinoma, although its underlying mechanism has received less attention than other types of metastases have. The objective of the current study was to confirm whether cancer stem cells (CSCs) in MPE contribute to the "metastatic cascade" through the epithelial - mesenchymal transition (EMT), anoikis, and adaptation in the microenvironment.
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Predictors of in-hospital mortality and prognosis in patients with large hemispheric stroke receiving decompressive craniectomy.
Br J Neurosurg
PUBLISHED: 12-15-2011
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Decompressive craniectomy reduces fatality in patients with space-occupying infarctions. However, mortality remains high. We aimed to identify predictors of in-hospital mortality and outcomes in a cohort of patients with large hemispheric stroke receiving decompressive craniectomy.
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Increased oxidative stress is responsible for severer cerebral infarction in stroke-prone spontaneously hypertensive rats.
CNS Neurosci Ther
PUBLISHED: 11-29-2011
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To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke-prone spontaneously hypertensive rats (SHR-SP).
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The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells.
J. Oral Pathol. Med.
PUBLISHED: 11-21-2011
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To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential.
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Effects of ketanserin on endotoxic shock and baroreflex function in rodents.
J. Infect. Dis.
PUBLISHED: 09-14-2011
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Ketanserin, a 5-hydroxytryptamine receptor antagonist, is clinically used as an antihypertensive agent and could enhance baroreflex function. The present work tested the hypothesis that restoration of baroreflex function is an effective treatment for lipopolysaccharide (LPS)-induced shock.
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Angiotensin-converting enzyme and Angiotensin-converting enzyme 2 are involved in sinoaortic denervation-induced cardiovascular hypertrophy in rats.
Biol. Pharm. Bull.
PUBLISHED: 09-02-2011
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The balance of angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) in high blood pressure variability (BPV) induced cardiovascular hypertrophy remains elusive. The aim of the present work was to investigate expression and activity of ACE and ACE2 in the heart and aorta of sinoaortic denervation (SAD) rats with high BPV and normal BP, and explore the potential role of ACE and ACE2 in high BPV-induced cardiovascular damage. Hemodynamics, cardiovascular hypertrophy, angiotensin II (Ang II) concentrations, ACE and ACE2 activity were determined. Cardiac-tissue ACE and ACE2 expression were assayed by real-time polymerase chain reaction and Western blot. Compared with sham-operated rats, systolic BPV and diastolic BPV increased and baroreflex sensitivity decreased significantly in SAD rats. SAD rats presented with obvious cardiovascular hypertrophy characterized by increased ratio of left ventricle weight to body weight and aortic weight to the length of aorta. There was no difference in plasma Ang II concentration between sham-operated and SAD rats. The cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity were elevated in SAD rats. There was no significant difference in cardiac ACE2 expressions between sham-operated and SAD rats. The present work demonstrated that cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity were increased in SAD rats. It is the tissue rather than the circulating renin-angiotensin system that contributes to high BPV-induced cardiovascular hypertrophy.
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Ubc9 expression predicts chemoresistance in breast cancer.
Chin J Cancer
PUBLISHED: 09-02-2011
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Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (?² = 6.538, P = 0.038), larger tumor size (?² = 4.701, P = 0.030), advanced clinical stage (?² = 4.651, P = 0.031), lymph node metastasis (?² = 9.913, P = 0.010), basal-like phenotype (?² = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (?² = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (?² = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.
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Radial basis function networks with linear interval regression weights for symbolic interval data.
IEEE Trans Syst Man Cybern B Cybern
PUBLISHED: 08-18-2011
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This paper introduces a new structure of radial basis function networks (RBFNs) that can successfully model symbolic interval-valued data. In the proposed structure, to handle symbolic interval data, the Gaussian functions required in the RBFNs are modified to consider interval distance measure, and the synaptic weights of the RBFNs are replaced by linear interval regression weights. In the linear interval regression weights, the lower and upper bounds of the interval-valued data as well as the center and range of the interval-valued data are considered. In addition, in the proposed approach, two stages of learning mechanisms are proposed. In stage 1, an initial structure (i.e., the number of hidden nodes and the adjustable parameters of radial basis functions) of the proposed structure is obtained by the interval competitive agglomeration clustering algorithm. In stage 2, a gradient-descent kind of learning algorithm is applied to fine-tune the parameters of the radial basis function and the coefficients of the linear interval regression weights. Various experiments are conducted, and the average behavior of the root mean square error and the square of the correlation coefficient in the framework of a Monte Carlo experiment are considered as the performance index. The results clearly show the effectiveness of the proposed structure.
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Baroreflex deficiency hampers angiogenesis after myocardial infarction via acetylcholine-?7-nicotinic ACh receptor in rats.
Eur. Heart J.
PUBLISHED: 08-17-2011
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Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats.
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Effects of wetland degradation on bacterial community in the Zoige Wetland of Qinghai-Tibetan Plateau (China).
World J. Microbiol. Biotechnol.
PUBLISHED: 08-02-2011
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Wetland degradation makes significant impacts on soil, and bacterial communities in soil are likely to respond to these impacts. The purpose of this study was to investigate the impacts of soil property, soil type and soil depth on bacterial community in different stages of soil degradation in the Zoige Wetland. Microbial biomass carbon was estimated from chloroform fumigation-extraction. Bacterial communities were evaluated by cluster and principal component analysis of DGGE banding patterns and sequencing of partial 16S rDNA PCR amplicons. Experimental results showed that microbial biomass carbon decreased with the soil types (Peat soil > Swamp soil > Meadow soil > Sandy soil) and declined with soil depths (0-20 > 20-40 > 40-60 cm). Bacterial community was affected by soil type more primarily than by soil depth. In addition, the microbial biomass carbon was strongly correlated with soil water content, soil organic carbon and total nitrogen. Sequence analysis of DGGE bands indicated that bacterial phyla of ?-Proteobacteria, ?-Proteobacteria, Bacteroidetes, Flavobacterium and Unidentified bacterium predominantly existed in the soil. All these results suggest that specific changes in soil property, soil type and soil depth affected soil bacterial community both quantitatively and qualitatively.
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Synergism of irbesartan and amlodipine on hemodynamic amelioration and organ protection in spontaneously hypertensive rats.
Acta Pharmacol. Sin.
PUBLISHED: 08-01-2011
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To investigate the synergism of low-doses of amlodipine and irbesartan on reduction of blood pressure variability (BPV), amelioration of baroreflex sensitivity (BRS) and organ protection in spontaneously hypertensive rats (SHR).
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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