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Find video protocols related to scientific articles indexed in Pubmed.
CCL5/CCR5 axis induces vascular endothelial growth factor-mediated tumor angiogenesis in human osteosarcoma microenvironment.
Carcinogenesis
PUBLISHED: 10-22-2014
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Chemokines modulate angiogenesis and metastasis that dictate cancer development in tumor microenvironment. Osteosarcoma is the most frequent bone tumor and is characterized by a high metastatic potential. Chemokine CCL5 (previously called RANTES) has been reported to facilitate tumor progression and metastasis. However, the crosstalk between chemokine CCL5 and vascular endothelial growth factor (VEGF) as well as tumor angiogenesis in human osteosarcoma microenvironment has not been well explored. In this study, we found that CCL5 increased VEGF expression and production in human osteosarcoma cells. The conditioned medium (CM) from CCL5-treated osteosarcoma cells significantly induced tube formation and migration of human endothelial progenitor cells. Pretreatment of cells with CCR5 antibody or transfection with CCR5 specific siRNA blocked CCL5-induced VEGF expression and angiogenesis. CCL5/CCR5 axis demonstrably activated protein kinase C? (PKC?), c-Src, and hypoxia-inducible factor-1 alpha (HIF-1?) signaling cascades to induce VEGF-dependent angiogenesis. Furthermore, knockdown of CCL5 suppressed VEGF expression and attenuated osteosarcoma CM-induced angiogenesis in vitro and in vivo. CCL5 knockdown dramatically abolished tumor growth and angiogenesis in the osteosarcoma xenograft animal model. Importantly, we demonstrated that the expression of CCL5 and VEGF were correlated with tumor stage according the immunohistochemistry analysis of human osteosarcoma tissues. Taken together, our findings provide evidence that CCL5/CCR5 axis promotes VEGF-dependent tumor angiogenesis in human osteosarcoma microenvironment through PKC?/c-Src/HIF-1? signaling pathway. CCL5 may represent a potential therapeutic target against human osteosarcoma.
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Two BN Isosteres of Anthracene: Synthesis and Characterization.
J. Am. Chem. Soc.
PUBLISHED: 10-14-2014
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The synthesis of two parental BN anthracenes, 1 and 2, was developed, and their electronic structure and reactivity behavior were characterized in direct comparison with all-carbon anthracene. Gas-phase UV-photoelecton spectroscopy studies revealed the following HOMO energy trend: anthracene, -7.4 eV; BN anthracene 1, -7.7 eV; bis-BN anthracene 2, -8.0 eV. The ?max of the lower energy band in the UV-vis absorption spectrum is as follows: anthracene, 356 nm; BN anthracene 1, 359 nm; bis-BN anthracene 2, 357 nm. Thus, although the HOMO is stabilized with increasing BN incorporation, the HOMO-LUMO band gap remains unchanged across the anthracene series. The emission ?max values for the three investigated anthracene compounds are at 403 nm. The pKa values of the N-H proton for BN anthracene 1 and bis-BN anthracene 2 were determined to be approximately 26. BN anthracenes 1 and 2 do not undergo heat- or light-induced cycloaddition reactions or Friedel-Crafts acylations. Electrophilic bromination of BN anthracene 1 with Br2, however, occurs regioselectively at the 9-position. The reactivity behavior and regioselectivity of bromination of BN anthracenes are consistent with the electronic structure of these compounds; i.e., (1) the lower HOMO energy levels for BN anthracenes stabilize the molecules against cycloaddition and Friedel-Crafts reactions, and (2) the HOMO orbital coefficients are consistent with the observed bromination regioselectivity. Overall, this work demonstrates that BN/CC isosterism can be used as a molecular design strategy to stabilize the HOMO of acene-type structures while the optical band gap is maintained.
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Influence of Superior Laryngeal Nerve Injury on Glottal Configuration/Function of Thyroidectomy-Induced Unilateral Vocal Fold Paralysis.
Otolaryngol Head Neck Surg
PUBLISHED: 09-13-2014
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Recurrent laryngeal nerve (RLN) injury may induce unilateral vocal fold paralysis (UVFP). During thyroidectomy, the most common cause of UVFP, the superior laryngeal nerve (SLN), is also at risk of injury. In the literature, the influence of SLN injury on glottal configuration and function in patients with UVFP remains controversial. The present study investigates SLN injury influence on glottal configuration and function in patients with UVFP after thyroidectomy.
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Inhibitory effects of butein on cancer metastasis and bioenergetic modulation.
J. Agric. Food Chem.
PUBLISHED: 09-03-2014
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Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment.
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Laryngeal electromyography and prognosis of unilateral vocal fold paralysis-A long-term prospective study.
Laryngoscope
PUBLISHED: 08-30-2014
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To confirm the value of using laryngeal electromyography (LEMG) to predict the long-term prognosis of unilateral vocal fold paralysis (UVFP), and elucidate the adequate timing of LEMG.
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Increased healthcare service utilizations for patients with dementia: a population-based study.
PLoS ONE
PUBLISHED: 08-26-2014
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The majority of previous studies investigating the health care utilization of people with dementia were conducted in Western societies. There is little information on the economic burden on the healthcare system attributable to dementia in Asian countries. This study thus investigated differences in utilization of healthcare services between subjects with and those without a diagnosis of dementia using Taiwan's National Health Insurance population-based database.
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Airway pH monitoring in patients with suspected obstructive sleep apnea using the Dx-pH oropharyngeal probe: preliminary report of a prospective cohort study.
Clin Otolaryngol
PUBLISHED: 08-13-2014
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To investigate the laryngopharyngeal reflux (LPR) episodes and pH values in patients with suspected obstructive sleep apnea (OSA) using the Dx-pH oropharyngeal probe.
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UV-photoelectron spectroscopy of BN indoles: experimental and computational electronic structure analysis.
J. Am. Chem. Soc.
PUBLISHED: 08-11-2014
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We present a comprehensive electronic structure analysis of two BN isosteres of indole using a combined UV-photoelectron spectroscopy (UV-PES)/computational chemistry approach. Gas-phase He I photoelectron spectra of external BN indole I and fused BN indole II have been recorded, assessed by density functional theory calculations, and compared with natural indole. The first ionization energies of these indoles are natural indole (7.9 eV), external BN indole I (7.9 eV), and fused BN indole II (8.05 eV). The computationally determined molecular dipole moments are in the order: natural indole (2.177 D) > fused BN indole II (1.512 D) > external BN indole I (0.543 D). The ?max in the UV-vis absorption spectra are in the order: fused BN indole II (292 nm) > external BN indole I (282 nm) > natural indole (270 nm). The observed relative electrophilic aromatic substitution reactivity of the investigated indoles with dimethyliminium chloride as the electrophile is as follows: fused BN indole II > natural indole > external BN indole I, and this trend correlates with the ?-orbital coefficient at the 3-position. Nucleus-independent chemical shifts calculations show that the introduction of boron into an aromatic 6?-electron system leads to a reduction in aromaticity, presumably due to a stronger bond localization. Trends and conclusions from BN isosteres of simple monocyclic aromatic systems such as benzene and toluene are not necessarily translated to the bicyclic indole core. Thus, electronic structure consequences resulting from BN/CC isosterism will need to be evaluated individually from system to system.
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Venous ligation: a novel strategy for glans enhancement in penile prosthesis implantation.
Biomed Res Int
PUBLISHED: 08-07-2014
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Although penile implantation remains a final solution for patients with refractory impotence, undesirable postoperative effects, including penile size reduction and cold sensation of the glans penis, remain problematic. We report results of a surgical method designed to avoid these problems. From 2003 to 2013, 35 consecutive patients received a malleable penile implant. Of these, 15 men (the enhancing group) were also treated with venous ligation of the retrocoronal venous plexus, deep dorsal vein, and cavernosal veins. The remaining 20 men formed the control group, treated with only a penile implant. Follow-up ranged from 1.1 to 10.0 years, with an average of 6.7 ± 1.5 years. Although preoperative glanular dimension did not differ significantly between the two groups, significant respective difference at one day and one year postoperatively was found in the glanular circumference (128.8 ± 6.8 mm versus 115.3 ± 7.2 mm and 130.6 ± 7.2 mm versus 100.5 ± 7.3 mm; both P<0.05), radius (38.8 ± 2.7 mm versus 37.1 ± 2.8 mm and 41.5 ± 2.6 mm versus 33.8 ± 2.9 mm; latter P<0.01), and satisfaction rate (91.7% versus 53.3%, P<0.01) as well. Based on our results, selective venous ligation appears to enhance the glans penis dimension in implant patients.
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Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.
J. Virol.
PUBLISHED: 07-30-2014
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Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-?/?]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-?), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-?), IFN-?, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. Importance: The host innate immune system is equipped with pattern recognition receptors (PRRs), which are useful for defending the host against invading pathogens. During enterovirus 71 (EV71) infection, the innate immune system is activated by pathogen-associated molecular patterns (PAMPs), which include viral RNA or DNA, and these PAMPs are recognized by PRRs. Toll-like receptor 3 (TLR3) and TLR7/8 recognize viral nucleic acids, and TLR9 senses unmethylated CpG DNA or pathogen-derived DNA. These PRRs stimulate the production of type I interferons (IFNs) to counteract viral infection, and they are the major source of antiviral alpha interferon (IFN-?) production in pDCs, which can produce 200- to 1,000-fold more IFN-? than any other immune cell type. In addition to PAMPs, danger-associated molecular patterns (DAMPs) are known to be potent activators of innate immune signaling, including TLR9. We found that EV71 induces cellular apoptosis, resulting in tissue damage; the endogenous DNA from dead cells may activate the innate immune system through TLR9. Therefore, our study provides new insights into EV71-induced apoptosis, which stimulates TLR9 in EV71-associated infections.
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Risk factors of recipient site infection in head and neck cancer patients undergoing pectoralis major myocutaneous flap reconstruction.
Eur Arch Otorhinolaryngol
PUBLISHED: 07-29-2014
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The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3 %) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and peri-operative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at risk.
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Depletion of tumor-associated macrophages enhances the anti-tumor immunity induced by a Toll-like receptor agonist-conjugated peptide.
Hum Vaccin Immunother
PUBLISHED: 07-08-2014
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It has been reported that lipopeptides can be used to elicit cytotoxic T lymphocyte (CTL) responses against viral diseases and cancer. In our previous study, we determined that mono-palmitoylated peptides can enhance anti-tumor responses in the absence of adjuvant activity. To investigate whether di-palmitoylated peptides with TLR2 agonist activity are able to induce anti-tumor immunity, we synthesized a di-palmitic acid-conjugated long peptide that contains a murine CTL epitope of HPV E7 49-57 (Pam2IDG). Pam2IDG stimulated the maturation of bone marrow-derived dendritic cells (BMDCs) through TLR2/6. After immunization, Pam2IDG induced higher levels of T cell responses than those obtained with its non-lipidated counterpart (IDG). In the prophylactic model, Pam2IDG immunization completely inhibited tumor growth, whereas IDG immunization was unable to inhibit tumor growth. However, Pam2IDG immunization could not effectively inhibit the growth of established tumors. Therefore, we further investigated whether the depletion of immunosuppressive factors could improve the therapeutic effects of Pam2IDG. Our data indicate that treatment with Pam2IDG combined with clodronate/liposome delays tumor growth and increases the survival rate. We also observed that the therapeutic effects of Pam2IDG are improved by diminishing the function of TAMs and through the use of an IL10 receptor blocking antibody or a Cox-2 inhibitor. In conclusion, the depletion of TAMs may enhance the anti-tumor immunity of a TLR2 agonist-conjugated peptide.
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Rhodium-catalyzed B-H activation of 1,2-azaborines: synthesis and characterization of BN isosteres of stilbenes.
Org. Lett.
PUBLISHED: 06-11-2014
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The first example of catalytic B-H activation of azaborines leading to a new family of stilbene derivatives through dehydrogenative borylation is reported. Ten 1,2-azaborine-based BN isosteres of stilbenes have been synthesized using this method, including a BN isostere of a biologically active stilbene. It is demonstrated that BN/CC isosterism in the context of stilbenes can lead to significant changes in the observed photophysical properties such as higher quantum yield and a larger Stokes shift. Direct comparative analysis of BN stilbene 3g and its carbonaceous counterpart 6g is consistent with a stronger charge-transfer character of the excited state exhibited by 3g in which the 1,2-azaborine heterocycle serves as a better electron donor than the corresponding arene.
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Suture cartilage formation pattern varies with different expansive forces.
Am J Orthod Dentofacial Orthop
PUBLISHED: 06-01-2014
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Midpalatal suture expansion could induce osteogenesis to correct maxillary insufficiency; cartilage formation could also be induced, and lower-magnitude forces might generate a preferable response pattern. In this study, we aimed for an enhanced understanding of the cartilage formatting effects of expansion.
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Safety and six-month durability of angioplasty for isolated penile artery stenoses in patients with erectile dysfunction: a first-in-man study.
EuroIntervention
PUBLISHED: 05-17-2014
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Obstructive pelvic arterial lesions are highly prevalent in patients with erectile dysfunction and commonly located in penile artery segments. In this first-in-man study, we intended to assess the safety and feasibility of balloon angioplasty for isolated penile artery stenoses in patients with erectile dysfunction.
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Delivery of human EV71 receptors by adeno-associated virus increases EV71 infection-induced local inflammation in adult mice.
Biomed Res Int
PUBLISHED: 05-14-2014
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Enterovirus71 (EV71) is now recognized as an emerging neurotropic virus in Asia and one major causative agent of hand-foot-mouth diseases (HFMD). However potential animal models for vaccine development are limited to young mice. In this study, we used an adeno-associated virus (AAV) vector to introduce the human EV71 receptors P-selectin glycoprotein ligand-1 (hPSGL1) or a scavenger receptor class-B member-2 (hSCARB2) into adult ICR mice to change their susceptibility to EV71 infection. Mice were administered AAV-hSCARB2 or AAV-hPSGL1 through intravenous and oral routes. After three weeks, expression of human SCARB2 and PSGL1 was detected in various organs. After infection with EV71, we found that the EV71 viral load in AAV-hSCARB2- or AAV-hPSGL1-transduced mice was higher than that of the control mice in both the brain and intestines. The presence of EV71 viral particles in tissues was confirmed using immunohistochemistry analysis. Moreover, inflammatory cytokines were induced in the brain and intestines of AAV-hSCARB2- or AAV-hPSGL1-transduced mice after EV71 infection but not in wild-type mice. However, neurological disease was not observed in these animals. Taken together, we successfully infected adult mice with live EV71 and induced local inflammation using an AAV delivery system.
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Salvianolic acid B maintained stem cell pluripotency and increased proliferation rate by activating Jak2-Stat3 combined with EGFR-Erk1/2 pathways.
Cell Transplant
PUBLISHED: 05-13-2014
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Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are considered the most powerful in terms of differentiating into three-germ-layer cells. However, maintaining self-renewing ESCs and iPSCs in vitro requires leukemia-induced factor (LIF), an expensive reagent. Here we describe a less expensive compound that may serve as a LIF substitute-salvianolic acid B (Sal B), a Salvia miltiorrhiza extract. We found that Sal B is capable of upregulating Oct4 and Sox2, two genes considered important for the maintenance of ESC pluripotency. Our MTT data indicate that instead of triggering cell death, Sal B induced cell proliferation, especially at optimum concentrations of 0.01 nM and 0.1 nM. Other results indicate that compared to non-LIF controls, Sal B-treated ESCs expressed higher levels of several stem cell markers while still maintaining differentiation into three-germ-layer cells after six passages. Further, we found that Sal B triggers the Jak2-Stat3 and EGFR-ERK1/2 signaling pathways. Following Sal B treatment, (a) levels of phosphorylated (p)-Jak2, p-Stat3, p-EGFR, and p-ERK proteins all increased; (b) these increases were suppressed by AG490 (a Jak2 inhibitor) and ZD1839 (an EGFR inhibitor); and (c) cytokines associated with the Jak2-Stat3 signaling pathway were upregulated. Our findings suggest that Sal B can be used as a LIF replacement for maintaining ESC pluripotency while increasing cell proliferation.
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Dryocrassin suppresses immunostimulatory function of dendritic cells and prolongs skin allograft survival.
Cell Transplant
PUBLISHED: 05-13-2014
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Dendritic cells (DCs) are the major specialized antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to monitor novel biological modifiers for the cure of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the emission of tumor necrosis factor-?, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was alleviated by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of I?B kinase, JNK/p38 mitogen-activated protein kinase, and the translocation of NF-?B. Treatment with dryocrassin noticeably diminished 2,4-dinitro-1-fluorobenzene-reduced delayed-type hypersensitivity and extended skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection via the destruction of DC maturation and function.
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Decellularization and recellularization technologies in tissue engineering.
Cell Transplant
PUBLISHED: 05-13-2014
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Decellularization is the process by which cells are discharged from tissues/organs, but all of the essential cues for cell preservation and homeostasis are retained in a three-dimensional structure of the organ and its extracellular matrix components. During tissue decellularization, maintenance of the native ultrastructure and composition of the extracellular matrix (ECM) is extremely acceptable. For recellularization, the scaffold/matrix is seeded with cells, the final goal being to form a practical organ. In this review, we focus on the biological properties of the ECM that remains when a variety of decellularization methods are used, comparing recellularization technologies, including bioreactor expansion for perfusion-based bioartificial organs, and we discuss cell sources. In the future, decellularization-recellularization procedures may solve the problem of organ assembly on demand.
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Comparison of stainless steel and titanium alloy orthodontic miniscrew implants: a mechanical and histologic analysis.
Am J Orthod Dentofacial Orthop
PUBLISHED: 04-08-2014
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The detailed mechanical and histologic properties of stainless steel miniscrew implants used for temporary orthodontic anchorage have not been assessed. Thus, the purpose of this study was to compare them with identically sized titanium alloy miniscrew implants.
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A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I.
Biochem. Pharmacol.
PUBLISHED: 04-06-2014
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Vorinostat, which is an extensively studied inhibitor against histone deacetylase (HDAC), shows limited clinical activity to solid tumors. WJ35435, a new hybrid of vorinostat and DACA (a topoisomerase inhibitor) potently inhibited HDAC activity (in particular HDAC1 and HDAC6) in kinase assay and cell-based examination. The anti-HDAC effect was confirmed by the induction of histone H3 acetylation and phosphorylation, ?-tubulin acetylation and ?-H2AX formation. WJ35435 showed better potency than vorinostat and DACA against PC-3 and DU-145, two human hormone-refractory metastatic prostate cancer (HRMPC) cell lines, but not benign prostate cells. WJ35435 at differential concentrations induced G1- or G2-phase arrest of the cell cycle in HRMPCs but not in benign prostate cells. WJ35435 induced the formation of topoisomerase I-DNA cleavable complexes but not type-II? or -II?. Topoisomerase activity assay confirmed the selective inhibition of topoisomerase I. WJ35435 induced profound DNA damage using comet tailing assay. WJ35435 was less effective than camptothecin and etoposide in inducing the phosphorylation and activation of Chk1, Chk2 and RPA32 which were crucial coordinators in DNA repair pathway, indicating a low DNA repair activity to WJ35435 action. Furthermore, WJ35435 showed an in vivo antitumor activity. A synergistic apoptosis (combination index=0.55) was obtained in combination between WJ35435 and MG-132 (a proteasome inhibitor). In summary, WJ35435 is a dual-targeted anticancer hybrid induces anti-HDAC and anti-topoisomerase I activities that cause DNA damage associated with a low DNA repair capability, and induce cell cycle arrest at G1- and G2-phase. Ultimately, WJ35435 inhibits cell proliferation and induces apoptosis of HRMPCs.
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Monobenzofused 1,4-azaborines: synthesis, characterization, and discovery of a unique coordination mode.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 04-01-2014
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We report the first general synthesis of boron-substituted monobenzofused 1,4-azaborines using ring-closing metathesis of an enamine-containing diene as a key synthetic strategy. As part of our investigations, we discovered that the B-C3 moiety in a 1,4-azaborine can serve uniquely as a ?(2)-L-type ligand. This functionality is exemplified by two ?(2)-N-?(2)-BC Pt complexes of a boron-pyridyl-substituted monobenzofused-1,4-azaborine. Single-crystal X-ray diffraction analysis of the Pt complexes shows a strong structural contribution from the iminium resonance form of the monobenzofused-1,4-azaborine ligand. We also demonstrate that a palladium(0) complex supported by a 1,4-azaborine-based phosphine ligand can catalyze hydroboration of 1-buten-3-yne with unique selectivity. In view of the importance of arene-metal ?-interactions in catalytic applications, this work should open new opportunities for ligand design involving the 1,4-azaborine motif as an arene substitute.
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Molecular mechanisms of TLR2-mediated antigen cross-presentation in dendritic cells.
J. Immunol.
PUBLISHED: 03-28-2014
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Cross-presentation is a key function of dendritic cells (DCs), which present exogenous Ags on MHC class I molecules to prime CTL responses. The effects of TLR triggering on the cross-presentation of exogenous Ags by DCs remain unclear. In this study, we used synthetic dipalmitoylated peptides and TLR2 agonist-conjugated peptides as models to elucidate the mechanisms of TLR2-mediated cross-presentation. We observed that the internalization of dipalmitoylated peptides by bone marrow-derived DCs was facilitated by TLR2 via clathrin-mediated endocytosis. The administration of these dipalmitoylated peptide-pulsed bone marrow-derived DCs eliminated established tumors through TLR2 signaling. We further demonstrated that the induction of Ag-specific CTL responses and tumor regression by dipalmitoylated peptides was TAP independent. In addition, presentation of dipalmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). The endocytosed dipalmitoylated peptide also passed rapidly from early endosome Ag-1-positive endosomes to RAS-related GTP-binding protein 7 (Rab7)-associated late endosomes compared with their nonlipidated counterparts. Furthermore, we found that dipalmitoylated peptide-upregulated Rab7 expression correlated with Ag presentation via the TLR2/MyD88 pathway. Both JNK and ERK signaling pathways are required for upregulation of Rab7. In summary, our data suggest that TLR2-mediated cross-presentation occurs through the upregulation of Rab7 and a TAP-independent pathway that prime CTL responses.
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Enhancement of diabetic wound repair using biodegradable nanofibrous metformin-eluting membranes: in vitro and in vivo.
ACS Appl Mater Interfaces
PUBLISHED: 03-06-2014
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This work developed biodegradable nanofibrous drug-eluting membranes that provided sustained release of metformin for repairing wounds associated with diabetes. To prepare the biodegradable membranes, poly-d-l-lactide-glycolide (PLGA) and metformin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and were spun into nanofibrous membranes by electrospinning. An elution method and an HPLC assay were utilized to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. The biodegradable nanofibrous membranes released high concentrations of metformin for more than three weeks. Moreover, nanofibrous metformin-eluting PLGA membranes were more hydrophilic and had a greater water-containing capacity than virgin PLGA fibers. The membranes also improved wound healing and re-epithelialization in diabetic rats relative to the control. The experimental results in this work suggest that nanofibrous metformin-eluting membranes were functionally active in the treatment of diabetic wounds and very effective as accelerators in the early stage of healing of such wounds.
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Technical procedures for template-guided surgery for mandibular reconstruction based on digital design and manufacturing.
Biomed Eng Online
PUBLISHED: 03-01-2014
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The occurrence of mandibular defects caused by tumors has been continuously increasing in China in recent years. Conversely, results of the repair of mandibular defects affect the recovery of oral function and patient appearance, and the requirements for accuracy and high surgical quality must be more stringent. Digital techniques--including model reconstruction based on medical images, computer-aided design, and additive manufacturing--have been widely used in modern medicine to improve the accuracy and quality of diagnosis and surgery. However, some special software platforms and services from international companies are not always available for most of researchers and surgeons because they are expensive and time-consuming.
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Finite element analysis of helical flows in human aortic arch: a novel index.
Biomicrofluidics
PUBLISHED: 03-01-2014
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This study investigates the helical secondary flows in the aortic arch using finite element analysis. The relationship between helical flow and the configuration of the aorta in patients of whose three-dimensional images constructed from computed tomography scans was examined. A finite element model of the pressurized root, arch, and supra-aortic vessels was developed to simulate the pattern of helical secondary flows. Calculations indicate that most of the helical secondary flow was formed in the ascending aorta. Angle ? between the zero reference point and the aortic ostium (correlation coefficient (r)?=?-0.851, P?=?0.001), the dispersion index of the cross section of the ascending (r?=?0.683, P?=?0.021) and descending aorta (r?=?0.732, P?=?0.010), all correlated closely with the presence of helical flow (P?
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Immunogenicity studies of bivalent inactivated virions of EV71/CVA16 formulated with submicron emulsion systems.
Biomed Res Int
PUBLISHED: 02-18-2014
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We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 ?g) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.
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A unique amidoanthraquinone derivative displays antiproliferative activity against human hormone-refractory metastatic prostate cancers through activation of LKB1-AMPK-mTOR signaling pathway.
Naunyn Schmiedebergs Arch. Pharmacol.
PUBLISHED: 02-17-2014
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Hormone-refractory metastatic prostate cancer (HRMPC), which is metastatic and resistant to hormone therapy, is an intractable problem in clinical treatment. Anthraquinone-based natural products and synthetic compounds have shown anticancer activity. However, cardiac toxicity is a major adverse reaction in these compounds. CC-36, a unique anthraquinone derivative, displayed higher antiproliferative activity in HRMPC than that in H9c2 cardiomyoblasts and normal prostate cells with the selectivity of five and twelve times, respectively. CC-36 caused G1 arrest of the cell cycle associated with an upregulation of p21 and downregulated levels of cyclin D1 and cyclin E expressions. Immunoprecipitation assay and Western blotting analysis showed that CC-36 triggered an increase of TSC1/TSC2 association and suppressed the phosphorylation of mammalian target of rapamycin (mTOR) (Ser2448) and p70 ribosomal protein S6 kinase (p70S6K) (Thr389), indicating the inhibition of both kinases' activities. CC-36 induced liver kinase B1 (LKB1) phosphorylation at Thr189, leading to LKB1 translocation from nucleus to cytosol for AMPK? phosphorylation (Thr172) and the kinase activation. The signaling pathway was validated using small interfering RNA (siRNA) technique with LKB1 knockdown. The combination treatment of MK2206 (a specific Akt inhibitor) with CC-36 showed a synergistic apoptosis in PC-3 cells indicating a potential combination strategy for LKB1 activators. Taken together, the data suggest that CC-36 displays anti-HRMPC activity through the activation of LKB1-AMPK pathway, leading to an inhibition of mTOR signaling and the induction of G1 arrest of the cell cycle. The combination use of Akt inhibitors with agents acting through LKB1-AMPK-mTOR pathway is a potential strategy for HRMPC treatment.
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Acceleration of re-endothelialization and inhibition of neointimal formation using hybrid biodegradable nanofibrous rosuvastatin-loaded stents.
Biomaterials
PUBLISHED: 02-09-2014
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Incomplete endothelialization and neointimal hyperplasia of injured arteries can cause acute and late stent thromboses. This work develops hybrid stent/biodegradable nanofibers for the local and sustained delivery of rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of rosuvastatin for four weeks. The effectiveness of the local delivery of rosuvastatin in reducing platelets was studied. The tissue inflammatory reaction caused by the hybrid stents that were used to treat diseased arteries was also documented. The proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. The results of this work provide insight into how patients with a high risk of stent restenosis should be treated for accelerating re-endothelialization and inhibiting neointimal hyperplasia.
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What interval characteristics make a good categorical disease assessment scale?
Phytopathology
PUBLISHED: 01-24-2014
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Plant pathologists most often obtain quantitative information on disease severity using visual assessments. Category scales have been used for assessing plant disease severity in field experiments, epidemiological studies, and for screening germplasm. The most widely used category scale is the Horsfall-Barratt (H-B) scale, but reports show that estimates of disease severity using the H-B scale are less precise compared with nearest percent estimates (NPEs) using the 0 to 100% ratio scale. Few studies have compared different category scales. The objective of this study was to compare NPEs, the H-B midpoint converted data, and four different linear category scales (5 and 10% increments, with and without additional grades at low severity [0.1, 0.5, 1.0, 2.0, 5.0, 10.0, 15.0, 20.0…100%, and 0.1, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 30.0…100%, respectively]). Results of simulations based on known distributions of disease estimation using the type II error rate (the risk of failing to reject H0 when H0 is false) showed that at disease severity ? 5%, a 10% category scale had a greater probability of failing to reject H0 when H0 is false compared with all other methods, while the H-B scale performed least well at 20 to 50% severity. The 5% category scale performed as well as NPEs except when disease severity was ? 1%. Both the 5 and 10% category scales with the additional grades included performed as well as NPEs. These results were confirmed with a mixed model analysis and bootstrap analysis of the original rater assessment data. A better knowledge of the advantages and disadvantages of category scale types will provide a basis for plant pathologists and plant breeders seeking to maximize accuracy and reliability of assessments to make an informed decision when choosing a disease assessment method.
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A purified recombinant lipopeptide as adjuvant for cancer immunotherapy.
Biomed Res Int
PUBLISHED: 01-15-2014
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Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter) induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs), leading to the secretion of TNF-? through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m) protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion). Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4). We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.
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Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy.
Mol. Cancer
PUBLISHED: 01-15-2014
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Although cytotoxic T lymphocytes (CTLs) play a major role in eradicating cancer cells during immunotherapy, the cancer-associated immunosuppressive microenvironment often limits the success of such therapies. Therefore, the simultaneous induction of cancer-specific CTLs and reversal of the immunosuppressive tumor microenvironment may be more effectively achieved through a single therapeutic vaccine. A recombinant lipoprotein with intrinsic Toll-like receptor 2 (TLR2) agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety (rlipo-E7m) has been demonstrated to induce robust CTL responses against small tumors. This treatment in combination with other TLR agonists is able to eliminate large tumors.
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Somatic mutations in the D-loop of mitochondrial DNA in head and neck squamous cell carcinoma.
Head Neck
PUBLISHED: 01-14-2014
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The purpose of this study was to characterize somatic mutations in the D-loop of mitochondrial DNA (mtDNA) and their impact on survival in patients with head and neck cancer.
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Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-access platform and standard laparoscopic instruments: Technical considerations and surgical outcomes.
Asian J Surg
PUBLISHED: 01-14-2014
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We previously reported our initial experience with laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-port device and conventional straight laparoscopic instruments.
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Association of dysmenorrhea with interstitial cystitis/bladder pain syndrome: a case-control study.
Acta Obstet Gynecol Scand
PUBLISHED: 01-06-2014
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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disabling condition of the urological system. Many gynecological conditions are reported to be associated with IC/BPS. This study presents epidemiological evidence of a possible association between dysmenorrhea and IC/BPS, using population-based data.
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Adsorption of silver ions on polypyrrole embedded electrospun nanofibrous polyethersulfone membranes.
J Colloid Interface Sci
PUBLISHED: 01-03-2014
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In this study we developed polypyrrole embedded electrospun nanofibrous polyethersulfone nanofibrous membranes for the removal of silver ions. Polypyrrole and polyethersulfone dissolved in N-methyl-2-pyrrolidone (NMP) were electrospun into nanofibrous membranes via an electrospinning process. The morphology of as-spun polypyrrole/polyethersulfone nanofibers was examined by scanning electron microscopy. The average diameter of electrospun nanofibers ranged from 410 nm to 540 nm. The adsorption capability of nanofibrous polypyrrole/polyethersulfone membranes was measured and compared with that of bulk polypyrrole. The influence of various process conditions on adsorption efficiency was also examined. The experimental results suggested that the electrospun nanofibrous membranes exhibited good silver ion uptake capabilities. The metal uptake of nanofibrous membranes increased with the initial metal ion concentrations and the pH value, while decreased with the temperature and the filtering rate of the solutions. Furthermore, the electrospun membrane could be reused after the recovery process.
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Herpes zoster is associated with prior statin use: a population-based case-control study.
PLoS ONE
PUBLISHED: 01-01-2014
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This study investigated the association between statin use and herpes zoster (HZ) occurrence in a population-based case-control study.
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Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.
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Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.
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Weekly and holiday-related patterns of panic attacks in panic disorder: a population-based study.
PLoS ONE
PUBLISHED: 01-01-2014
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While chronobiological studies have reported seasonal variation in panic attacks (PA) episodes, information on the timing of PA by week-days may enable better understanding of the triggers of PA episodes and thereby provide pointers for suitable interventional approaches to minimize PA attacks. This study investigated weekly variation in potential PA admissions including associations with holidays using a population-based longitudinal, administrative claims-based dataset in an Asian population.
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Increased risk of pneumonia in patients receiving gonadotropin-releasing hormone agonists for prostate cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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This study aimed to investigate the relationship between the use of gonadotropin-releasing hormone (GnRH) agonists and subsequent risk of pneumonia in patients with prostate cancer (PC) using a population-based dataset.
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Health care service utilization among patients with bladder pain syndrome/interstitial cystitis in a single payer healthcare system.
PLoS ONE
PUBLISHED: 01-01-2014
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This study aims to investigate the differences in the utilization of healthcare services between patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and patients without using a population-based database in Taiwan.
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Local sustained delivery of acetylsalicylic acid via hybrid stent with biodegradable nanofibers reduces adhesion of blood cells and promotes reendothelialization of the denuded artery.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a highperformance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.
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n-butylidenephthalide protects against dopaminergic neuron degeneration and ?-synuclein accumulation in Caenorhabditis elegans models of Parkinson's disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system that impairs motor skills and cognitive function. To date, the disease has no effective therapies. The identification of new drugs that provide benefit in arresting the decline seen in PD patients is the focus of much recent study. However, the lengthy time frame for the progression of neurodegeneration in PD increases both the time and cost of examining potential therapeutic compounds in mammalian models. An alternative is to first evaluate the efficacy of compounds in Caenorhabditis elegans models, which reduces examination time from months to days. n-Butylidenephthalide is the naturally-occurring component derived from the chloroform extract of Angelica sinensis. It has been shown to have anti-tumor and anti-inflammatory properties, but no reports have yet described the effects of n-butylidenephthalide on PD. The aim of this study was to assess the potential for n-butylidenephthalide to improve PD in C. elegans models.
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Disintegration and cancer immunotherapy efficacy of a squalane-in-water delivery system emulsified by bioresorbable poly(ethylene glycol)-block-polylactide.
Biomaterials
PUBLISHED: 09-09-2013
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Vaccine adjuvant is conferred on the substance that helps to enhance antigen-specific immune response. Here we investigated the disintegration characteristics and immunotherapy potency of an emulsified delivery system comprising bioresorbable polymer poly(ethylene glycol)-polylactide (PEG-PLA), phosphate buffer saline (PBS), and metabolizable oil squalane. PEG-PLA-stabilized oil-in-water emulsions show good stability at 4 °C and at room temperature. At 37 °C, squalane/PEG-PLA/PBS emulsion with oil/aqueous weight ratio of 7/3 (denominated PELA73) was stable for 6 weeks without phase separation. As PEG-PLA being degraded, 30% of free oil at the surface layer and 10% of water at the bottom disassociated from the PELA73 emulsion were found after 3 months. A MALDI-TOF MS study directly on the DIOS plate enables us to identify low molecular weight components released during degradation. Our results confirm the loss of PLA moiety of the emulsifier PEG-PLA directly affected the stability of PEG-PLA-stabilized emulsion, leading to emulsion disintegration and squalane/water phase separation. As adjuvant for cancer immunotherapeutic use, an HPV16 E7 peptide antigen formulated with PELA73 plus immunostimulatory CpG molecules could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated or Alum-formulated peptide. Accordingly, these advances may be a potential immunoregulatory strategy in manipulating the immune responses induced by tumor-associated antigens.
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Lipidated dengue-2 envelope protein domain III independently stimulates long-lasting neutralizing antibodies and reduces the risk of antibody-dependent enhancement.
PLoS Negl Trop Dis
PUBLISHED: 09-01-2013
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Dengue virus is a mosquito-transmitted virus that can cause self-limiting dengue fever, severe life-threatening dengue hemorrhagic fever and dengue shock syndrome. The existence of four serotypes of dengue virus has complicated the development of an effective and safe dengue vaccine. Recently, a clinical phase 2b trial of Sanofi Pasteurs CYD tetravalent dengue vaccine revealed that the vaccine did not confer full protection against dengue-2 virus. New approaches to dengue vaccine development are urgently needed. Our approach represents a promising method of dengue vaccine development and may even complement the deficiencies of the CYD tetravalent dengue vaccine.
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3-Methyl-1,2-BN-cyclopentane: a promising H2 storage material?
Dalton Trans
PUBLISHED: 08-24-2013
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We provide detailed characterization of properties for 3-methyl-1,2-BN-cyclopentane 1 that are relevant to H(2) storage applications such as viscosity, thermal stability, H(2) gas stream purity, and polarity. The viscosity of 1 at room temperature is 25 ± 5 cP, about one fourth the viscosity of olive oil. TGA/MS analysis indicates that liquid carrier 1 is thermally stable at 30 °C but decomposes slowly at 50 °C. RGA data suggest that the H(2) desorption from 1 is a clean process, producing relatively pure H(2) gas. Compound 1 is a polar zwitterionic-type liquid consistent with theoretical predictions and solvatochromic studies.
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Protecting group-free synthesis of 1,2-azaborines: a simple approach to the construction of BN-benzenoids.
J. Am. Chem. Soc.
PUBLISHED: 08-19-2013
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The protecting group-free synthesis of a versatile 1,2-azaborine synthon 5 is described. Previously inaccessible 1,2-azaborine derivatives, including the BN isostere of phenyl phenylacetate and BN1 triphenylmethane were prepared from 5 and characterized. The structural investigation of BN phenyl phenylacetate revealed the presence of a unique NH-carbonyl hydrogen bond that is not present in the corresponding carbonaceous analogue. The methyne CH in BN triphenylmethane was found to be less acidic than the corresponding proton in triphenylmethane. The gram-quantity synthesis of the parent 1,2-azaborine 4 was demonstrated, which enabled the characterization of its boiling point, density, refractive index, and its polarity on the ET(30) scale.
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A novel emulsion-type adjuvant containing CpG oligodeoxynucleotides enhances CD8(+) T-cell-mediated anti-tumor immunity.
J Control Release
PUBLISHED: 08-15-2013
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PELC is a novel emulsion-type adjuvant that contains the bioresorbable polymer poly (ethylene glycol)-block-poly (lactide-co-?-caprolactone) (PEG-b-PLACL), Span®85 and squalene. To investigate whether PELC is able to enhance CTL responses of antigens for treating tumor, peptides or protein antigens derived from HPV16 E7 were formulated with PELC nanoparticles and CpG oligodeoxynucleotide. We identified that PELC formulation could delay the release of antigens in vitro and in vivo. We assessed the immunogenicity of an H-2D(b)-restricted CTL epitope RAHYNIVTF (RAH) formulated with PELC or PELC/CpG and investigated the ability of these formulations to promote tumor regression. Following a single-dose subcutaneous injection in mice, we found that the RAH peptide formulated with PELC/CpG (RAH/PELC/CpG) resulted in increased numbers of IFN-?-secreting cells and RAH-specific CD8(+) T cells and an enhanced cytotoxic T cell response compared with RAH formulated with PELC or CpG alone. The tumor-bearing mice received a single-dose injection of RAH/PELC/CpG, which induced complete tumor regression. These results demonstrated that peptide antigen formulated with PELC/CpG nanoparticles is feasible for cancer immunotherapy.
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Biodegradable drug-eluting poly[lactic-co-glycol acid] nanofibers for the sustainable delivery of vancomycin to brain tissue: in vitro and in vivo studies.
ACS Chem Neurosci
PUBLISHED: 07-12-2013
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Successful treatment of a brain infection requires aspiration of the pus or excision of the abscess, followed by long-term (usually 4-8 weeks) parenteral antibiotic treatment. Local antibiotic delivery using biodegradable drug-impregnated carriers is effective in treating postoperative infections, thereby reducing the toxicity associated with parenteral antibiotic treatment and the expense involved with long-term hospitalization. We have developed vancomycin-loaded, biodegradable poly[lactic-co-glycol acid] nanofibrous membranes for the sustainable delivery of vancomycin to the brain tissue of rats by using the electrospinning technique. A high-performance liquid chromatography assay was employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the membranes. The experimental results suggested that the biodegradable nanofibers can release high concentrations of vancomycin for more than 8 weeks in the cerebral cavity of rats. Furthermore, the membranes can cover the wall of the cavity after the removal of abscess more completely and achieve better drug delivery without inducing adverse mass effects in the brain. Histological examination also showed no inflammation reaction of the brain tissues. By adopting the biodegradable, nanofibrous drug-eluting membranes, we will be able to achieve long-term deliveries of various antibiotics in the cerebral cavity to enhance the therapeutic efficacy of cerebral infections.
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Biodegradable poly([D,L]-lactide-co-glycolide) nanofibers for the sustainable delivery of lidocaine into the epidural space after laminectomy.
Nanomedicine (Lond)
PUBLISHED: 06-26-2013
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Aim: We developed biodegradable, lidocaine-embedded poly([D,L]-lactide-co-glycolide) nanofibers for epidural analgesia to reduce the severe pain in rats after laminectomies. Materials & methods: Nanofibers were prepared by an electrospinning process and were introduced into the epidural space of rats after laminectomy. The lidocaine concentration, postoperative bodyweight change and amount of food/water intake were monitored to evaluate the analgesic effectiveness of the drug-eluting nanofibers. Results: It was demonstrated that the nanofibers provided a sustained release of lidocaine for more than 2 weeks, and the local pharmaceutical concentration was much higher than the concentration in plasma. Rats that received laminectomies without nanofibers exhibited the greatest bodyweight reduction. The food/water intake and activity performance were significantly higher in rats receiving laminectomies with nanofibers than in rats without nanofibers. Conclusion: The results of this study suggest that the lidocaine-loaded nanofibers can provide an easy, practical and safe means of achieving effective postlaminectomy analgesia. Original submitted 23 April 2012; Revised submitted 25 October 2012; Published online 26 June 2013.
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Carotid blowout in head and neck cancer patients - associated factors and treatment outcomes.
Head Neck
PUBLISHED: 06-18-2013
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Background: We investigate factors associated with carotid blowout in the cervical portion of head and neck patients in a large cohort. Methods: We reviewed head and neck cancer patients and identified those with carotid blowout. Variables of patients with and without carotid blowout were compared and associated factors were investigated by logistic regression model. Results: A total of 2590 patients were included in the final analysis and 102 patients (3.9%) developed carotid blowout in the cervical region. Body mass index < 22.5 kg/M(2) , primary site of hypopharynx or oropharynx, open wound in the neck requiring wet dressing, radical neck dissection, and total radiation dose to the neck >= 70 Gy were independent factors associated with carotid blowout. Conclusions: After completion of treatment in head and neck cancer patients, carotid blowout was an uncommon complication with catastrophic results. Recognition of associated factors helps physician to identify those in risk. Head Neck, 2013.
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Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III.
Microbes Infect.
PUBLISHED: 04-15-2013
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Many attempts have focused on the use of either immunomodulators or antigen delivery systems to obtain an efficacious vaccine. Here, we report a novel approach that combined an immunomodulator and delivery system to enhance antigen association and induce robust immunity. We expressed a recombinant lipidated dengue-1 envelope protein domain III (LD1ED III) and its non-lipidated form, D1ED III, in an Escherichia coli system. The LD1ED III contains a bacterial lipid moiety, which is a potent immunomodulator. We demonstrated that LD1ED III possesses an inherent immunostimulation ability that can activate RAW 264.7 macrophage cells by up-regulating their expression of CD40, CD80, CD83, CD86 and MHC II, whereas D1ED III could not induce the up-regulation of these molecules. Moreover, combining LD1ED III with a multiphase emulsion system (called PELC) increased the antigen association more than either combining D1ED III with PELC or the antigen alone. Enhanced antigen association has been shown to correlate with stronger T cell responses, greater antibody avidity and improved neutralizing capacity. Our results demonstrate that combining recombinant lipoproteins with PELC improved both the intensity and the quality of the immune response. This approach is a promising strategy for the development of subunit vaccines that induce robust immunity.
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Boron-substituted 1,3-dihydro-1,3-azaborines: synthesis, structure, and evaluation of aromaticity.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 03-30-2013
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Getting the family together: A general synthetic strategy based on nucleophilic substitution provided B-substituted 1,3-dihydro-1,3-azaborines (see scheme), BN isosteres of arenes with potential for application in biomedicine and materials science. Experimental structural analysis and calculations suggest that the aromaticity of the 1,3-dihydro-1,3-azaborine heterocycle is intermediate between that of benzene and that of 1,2-dihydro-1,2-azaborine.
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Effects of platelet-rich plasma and recombinant human bone morphogenetic protein-2 on suture distraction osteogenesis.
J Craniofac Surg
PUBLISHED: 03-26-2013
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Growth factors contained in platelet-rich plasma (PRP) have been reported to induce osteoblast differentiation in certain studies, while in others, osteogenesis has not been shown clinically. The aim of the present study was to verify the effect of PRP and its combination with rhBMP-2 as a controlled delivery system during sagittal suture distraction osteogenesis.
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Acetylcorynoline attenuates dopaminergic neuron degeneration and ?-synuclein aggregation in animal models of Parkinsons disease.
Neuropharmacology
PUBLISHED: 03-24-2013
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Parkinsons disease (PD), the second most common neurodegenerative disease, impairs motor skills and cognitive function. To date, the drugs used for PD treatment provide only symptomatic relief. The identification of new drugs that show benefit in slowing the decline seen in PD patients is the focus of much current research. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana, a traditional Chinese medical herb. It has been shown to have anti-inflammatory properties, but no studies have yet described the effects of acetylcorynoline on PD. The aim of this study was to evaluate the potential for acetylcorynoline to improve PD in Caenorhabditis elegans models. In the present study, we used a pharmacological strain (BZ555) that expresses green fluorescent protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that expresses human ?-synuclein in muscle cells to study the antiparkinsonian effects of acetylcorynoline. Our experimental data showed that treatment with up to 10 mM acetylcorynoline does not cause toxicity in animals. Acetylcorynoline significantly decreases dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; prevents ?-synuclein aggregation; recovers lipid content in OW13 strain; restores food-sensing behavior, and dopamine levels; and prolongs life-span in 6-hydroxydopamine-treated N2 strain, thus showing its potential as a possible antiparkinsonian drug. Acetylcorynoline may exert its effects by decreasing egl-1 expression to suppress apoptosis pathways and by increasing rpn5 expression to enhance the activity of proteasomes. This article is part of a Special Issue entitled Neurodegenerative Disorders.
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Trichodermin induces cell apoptosis through mitochondrial dysfunction and endoplasmic reticulum stress in human chondrosarcoma cells.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-21-2013
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Chondrosarcoma is the second most common primary bone tumor, and it responds poorly to both chemotherapy and radiation treatment. Nalanthamala psidii was described originally as Myxosporium in 1926. This is the first study to investigate the anti-tumor activity of trichodermin (trichothec-9-en-4-ol, 12,13-epoxy-, acetate), an endophytic fungal metabolite from N. psidii against human chondrosarcoma cells. We demonstrated that trichodermin induced cell apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 cells) instead of primary chondrocytes. In addition, trichodermin triggered endoplasmic reticulum (ER) stress protein levels of IRE1, p-PERK, GRP78, and GRP94, which were characterized by changes in cytosolic calcium levels. Furthermore, trichodermin induced the upregulation of Bax and Bid, the downregulation of Bcl-2, and the dysfunction of mitochondria, which released cytochrome c and activated caspase-3 in human chondrosarcoma. In addition, animal experiments illustrated reduced tumor volume, which led to an increased number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells and an increased level of cleaved PARP protein following trichodermin treatment. Together, this study demonstrates that trichodermin is a novel anti-tumor agent against human chondrosarcoma cells both in vitro and in vivo via mitochondrial dysfunction and ER stress.
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Survival analysis of patients with oral squamous cell carcinoma with simultaneous second primary tumors.
Head Neck
PUBLISHED: 03-09-2013
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The purpose of this study was to investigate the rate of simultaneous second primary tumor (SPT) in patients with oral squamous cell carcinoma. The survival of patients with simultaneous SPT was also compared with patients without.
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Recombinant human bone morphogenetic protein-2 stimulates bone formation during interfrontal suture expansion in rabbits.
Am J Orthod Dentofacial Orthop
PUBLISHED: 03-01-2013
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Suture expansion stimulates bone growth to correct craniofacial deficiencies but has a high potential of treatment relapse. The objective of this study was to investigate whether there is a dose-dependent relationship between the recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone formation during suture expansion.
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BN isosteres of indole.
Org. Biomol. Chem.
PUBLISHED: 02-14-2013
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Indole is a heterocycle of great importance to biological systems and materials applications. Synthesis of indole and its derivatives has been a major focus of research for over a century. BN/CC isosterism is an emerging strategy for expanding the structural diversity of indole-based compounds. Two classes of BN indoles have been reported to date: the well-studied "external" BN indoles (or 1,3,2-benzodiazaborolines), and the recently reported "fused" BN indoles. This perspective presents the history of both classes of indole isosteres, with a general overview of their synthesis, functionalization, and properties.
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Acetylcorynoline impairs the maturation of mouse bone marrow-derived dendritic cells via suppression of I?B kinase and mitogen-activated protein kinase activities.
PLoS ONE
PUBLISHED: 02-04-2013
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Dendritic cells (DCs) are major modulators in the immune system. One active field of research is the manipulation of DCs as pharmacological targets to screen novel biological modifiers for the treatment of inflammatory and autoimmune disorders. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana herbs. We assessed the capability of acetylcorynoline to regulate lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs.
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Personality traits as a potential predictor of willingness to undergo various orthodontic treatments.
Angle Orthod
PUBLISHED: 02-01-2013
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To establish an association between patient personality traits and potential willingness to undergo various orthodontic treatments.
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Obstructive Sleep Apnea Increases the Risk of Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Matched-Cohort Study.
Neurourol. Urodyn.
PUBLISHED: 01-29-2013
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AIMS: Previous studies indicated a possible association between bladder pain syndrome/interstitial cystitis (BPS/IC) and sleep disorders including sleep abnormalities with delayed onset of sleep, waking up before needed, and snoring. Nevertheless, no previous study has reported the association between obstructive sleep apnea (OSA) and BPS/IC. In this retrospective cohort study, we examined the risk of BPS/IC among subjects with OSA during a 3-year follow-up in Taiwan using a population-based dataset. METHODS: This study comprised 2,940 study subjects with OSA, and 29,400 randomly selected comparison subjects. We individually followed-up each sampled subject (n?=?32,340) for a 3-year period to identify those subjects who subsequently received a diagnosis of BPS/IC. A Cox proportional hazards regression model was constructed to estimate the risk of subsequent BPS/IC following a diagnosis of OSA. RESULTS: Incidences of BPS/IC during the 3-year follow-up period were 13.61 (95% confidence interval [CI]?=?7.37-23.13) and 3.60 (95% CI?=?2.06-4.39) for subjects with and those without OSA, respectively. After adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, asthma, tobacco use disorder, and alcohol abuse, the stratified Cox proportional hazards regressions revealed that the hazard ratio for BPS/IC among subjects with OSA was 3.71 (95% CI?=?1.81-7.62, P?
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BN/CC isosteric compounds as enzyme inhibitors: N- and B-ethyl-1,2-azaborine inhibit ethylbenzene hydroxylation as nonconvertible substrate analogues.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 01-28-2013
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Good substrate gone bad! BN/CC isosterism of ethylbenzene leads to N-ethyl-1,2-azaborine and B-ethyl-1,2-azaborine. In contrast to ethylbenzene, which is the substrate for ethylbenzene dehydrogenase (EbDH), N-ethyl-1,2-azaborine (see scheme; Fc=Ferricenium tetrafluoroborate) and B-ethyl-1,2-azaborine are strong inhibitors of EbDH. Thus, the changes provided by BN/CC isosterism can lead to new biochemical reactivity.
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Biodegradable cisplatin-eluting tracheal stent for malignant airway obstruction: in vivo and in vitro studies.
Chest
PUBLISHED: 01-26-2013
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Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems.
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Association between prostate cancer and urinary calculi: a population-based study.
PLoS ONE
PUBLISHED: 01-25-2013
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Understanding the reasons underlying the emerging trend and the changing demographics of Asian prostate cancer (PC) has become an important field of study. This study set out to explore the possibility that urinary calculi (UC) and PC may share an association by conducting a case-control study on a population-based database in Taiwan.
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Bladder pain syndrome/interstitial cystitis is associated with anxiety disorder.
Neurourol. Urodyn.
PUBLISHED: 01-17-2013
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Recent research demonstrated that bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with many coexisting physical and psychiatric conditions. In this study, we explored the potential association between anxiety disorder (AD) and BPS/IC using a case-controlled population-based approach in Taiwan.
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Association between schizophrenia and urinary calculi: a population-based case-control study.
PLoS ONE
PUBLISHED: 01-16-2013
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People with schizophrenia have been demonstrated to have higher overall morbidity and all-cause mortality rates from general medical conditions. However, little attention has been given to the urinary system of people with schizophrenia. As no direct evidence has been reported demonstrating a link between schizophrenia and urinary calculi, this study utilized a population-based case-control study design to investigate the possibility of an association between schizophrenia and the occurrence of urinary calculi.
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Sustainable release of carmustine from biodegradable poly[((D,L))-lactide-co-glycolide] nanofibrous membranes in the cerebral cavity: in vitro and in vivo studies.
Expert Opin Drug Deliv
PUBLISHED: 01-07-2013
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Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. The only interstitial chemotherapy pharmaceutical approved to date for GBM treatment is the Gliadel® wafer. Despite the safety and efficacy of this approach that have been demonstrated in patients undergoing resection of both newly diagnosed and recurrent malignant gliomas, the wafer provides an effective release of the anticancer 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for only 5 days.
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