JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Upregulation of Stat1-HDAC4 confers resistance to etoposide through enhanced multidrug resistance 1 expression in human A549 lung cancer cells.
Mol Med Rep
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
Despite efforts to develop efficient chemotherapeutic drug strategies to treat cancer, acquired drug resistance is a commonly encountered problem. In the present study, to investigate this phenomenon, human A549 lung cancer cells resistant to the topoisomerase inhibitor etoposide (A549RT?eto) were used and compared with A549 parental cells. A549RT?eto cells demonstrated increased resistance to etoposide?induced apoptosis when compared with A549 parental cells. Notably, A549RT?eto cells were observed to exhibit greater levels of histone deacetylase 4 (HDAC4), phospho?Stat1 and P?glycoprotein [P?gp; encoded by the multidrug resistance 1 (MDR1) gene], compared with A549 cells. To address whether HDAC4 protein is involved in etoposide resistance in A549 cells, A549RT?eto cells were treated with trichostatin A (TSA; an HDAC inhibitor) during etoposide treatment. The combined treatment was demonstrated to enhance etoposide?induced apoptosis and reduce expression levels of HDAC4, P?gp and phospho?Stat1. In addition, the suppression of Stat1 with siRNA enhanced etoposide?induced apoptosis and reduced the expression levels of HDAC4 and P?gp, suggesting that Stat1 is essential in the regulation of resistance to etoposide, and in the upregulation of P?gp. Notably, TSA treatment reduced P?gp transcript levels but Stat1 siRNA treatment did not, suggesting that P?gp is regulated by HDAC at the transcriptional level and by Stat1 at the post?transcriptional level. These results suggest that the upregulation of Stat1 and HDAC4 determines etoposide resistance through P?gp expression in human A549 lung cancer cells.
Related JoVE Video
Anti-inflammatory activity of SMP30 modulates NF-?B through protein tyrosine kinase/phosphatase balance.
J. Mol. Med.
PUBLISHED: 10-23-2014
Show Abstract
Hide Abstract
Recent studies on senescence marker protein-30 (SMP30) have shown that it has an important functional role in the aging process, but its precise participation in cellular works has not been fully determined. We hypothesize that SMP30 plays crucial roles in signaling processes by modulating the balance of protein tyrosine kinase (PTK)/protein tyrosine phosphatase (PTP) and in activating proinflammatory NF-?B. An experimental paradigm of gain and loss of SMP30 function was established using SMP30-overexpressed YPEN-1 cells (herein referred to as "SMP30(+) cells") and SMP30 (Y/-) knockout mouse kidneys. The resulting data show that SMP30 expression suppressed oxidative stress-induced PTK/PTP dysregulation and PP1/2A inactivation in SMP30(+) cells, leading to the suppression of NF-?B activation. In the kidneys of SMP30 (Y/-) mice, SMP30 deficiency was found to induce NF-?B activation via the upstream signaling of NIK/IKK and MAPKs and to upregulate downstream NF-?B-responsive gene expression. In this study, we also demonstrate for the first time that SMP30 deficiency induced PTK activity in SMP30 (Y/-) kidneys, thereby significantly increasing the tyrosine phosphorylation of a catalytic subunit of PP2A (PP2Ac-Tyr307). Based on these findings, we propose that SMP30 involves NF-?B regulation through the PTK/PTP balance and that the age-related decrease of SMP30 causes NF-?B activation, which contributes to an exacerbation of the inflammatory process during aging.
Related JoVE Video
Delay in the recovery of normal sleep-wake cycle after disruption of the light-dark cycle in mice: a bipolar disorder-prone animal model?
Psychiatry Investig
PUBLISHED: 10-20-2014
Show Abstract
Hide Abstract
Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice.
Related JoVE Video
Metastatic tumor antigen in hepatocellular carcinoma: golden roads toward personalized medicine.
Cancer Metastasis Rev.
PUBLISHED: 10-19-2014
Show Abstract
Hide Abstract
Hepatocellular carcinoma (HCC), a prototype of hypervascular tumors, is one of the most common malignancies in the world, especially hyperendemic in the Far East where chronic hepatitis B virus (HBV) infection is highly prevalent. It is characterized by the clinical feature of a poor prognosis or a high mortality due to its already far advanced stages at diagnosis. It is so multifactorial that hepatocarcinogenesis cannot be explained by a single molecular mechanism. To date, a number of pathways have been known to contribute to the development, growth, angiogenesis, and even metastasis of HCC. Among the various factors, metastatic tumor antigens (MTAs) or metastasis-associated proteins have been vigorously investigated as an intriguing target in the field of hepatocarcinogenesis. According to recent studies including ours, MTAs are not only involved in the HCC development and growth (molecular carcinogenesis), but also closely associated with the post-operative recurrence and a poor prognosis or a worse response to post-operative anti-cancer therapy (clinical significance). Herein, we review MTAs in light of their essential structure, functions, and molecular mechanism in hepatocarcinogenesis. We will also focus in detail on the interaction between hepatitis B x protein (HBx) of HBV and MTA in order to clarify the HBV-associated HCC development. Finally, we will discuss the prognostic significance and clinical application of MTA in HCC. We believe that this review will help clinicians to understand the meaning and use of the detection of MTA in order to more effectively manage their HCC patients.
Related JoVE Video
Tumor Necrosis Factor-Alpha Gene Polymorphism Associated With Development of Hepatitis B Virus-associated Hepatocellular Carcinoma.
J. Clin. Gastroenterol.
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
Host genetic diversity may play roles in development of HCC. This study was conducted to validate the effects of tumor necrosis factor-alpha (TNF-?) gene polymorphism on development of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV).
Related JoVE Video
Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 08-27-2014
Show Abstract
Hide Abstract
Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased ?-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3? (FOXO3?) by SIRT1 changed the transcriptional activity of FOXO3? and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging.
Related JoVE Video
Salicylideneamino-2-thiophenol modulates nuclear factor-?B through redox regulation during the aging process.
Geriatr Gerontol Int
PUBLISHED: 08-27-2014
Show Abstract
Hide Abstract
Many intracellular components have been implicated in the regulation of redox homeostasis, but homeostasis can be unbalanced by reactive species (RS), which also probably contribute to underlying inflammatory processes. Nuclear factor-?B (NF-?B) is a well-known redox-sensitive transcription factor that controls the genes responsible for regulating inflammation.
Related JoVE Video
The roles of FoxOs in modulation of aging by calorie restriction.
Biogerontology
PUBLISHED: 08-22-2014
Show Abstract
Hide Abstract
FoxO activity and modifications, such as its phosphorylation, acetylation, and methylation, may help drive the expression of genes involved in combating oxidative stress by causing the epigenetic modifications, and thus, preserve cellular function during aging and age-related diseases, such as diabetes, cancer, and Alzheimer disease. Insulin signaling has been postulated to influence the aging process by increasing resistance to oxidative stress, and slowing the accumulation of oxidative damage. Some antioxidative effects are mediated by a conserved family of forkhead box transcription factors (FoxOs), which in the absence of insulin signaling freely bind to promoters of antioxidant enzymes, superoxide dismutase, and catalase. On the other hand, calorie restriction (CR) extends the lifespans of several species via the insulin pathway, and extends longevity and healthspan in diverse species via a conserved mechanism. CR enhances adaptive stress responses at the cellular and organism levels and extends lifespan in a FoxO-independent manner. Thus, increased modification of FoxO is modulated via the hyperinsulinemia-induced PI3K/Akt pathway during aging, and CR reverses this process. Accordingly, FoxO plays an important role in maintenance of metabolic homeostasis and removal of oxidative stress in the aging process and in the effect of CR on lifespan.
Related JoVE Video
Modulation of Colitis-associated Colon Tumorigenesis by Baicalein and Betaine.
J Cancer Prev
PUBLISHED: 08-16-2014
Show Abstract
Hide Abstract
In this review, we will summarize the current understanding of modulation of colitis-associated colon tumorigenesis by two natural products, baicalein and betaine, which have anti-inflammatory activities. Baicalein and betaine have been shown to provide various health benefits to organism in many ways. Baicalein is a phenolic flavonoid derived originally from the root of Scutellaria baicalensis Georgi. From ancient times, baicalein has widely been used in oriental medicines as an anti-inflammatory and anti-cancer therapy. Betaine, trimethylglycine, is an essential biochemical molecule of the methionine/homocysteine cycle and is synthesized by conversion of choline. Betaine is an important human nutrient obtained from various foods including sugar beet and lycium. Betaine has provided various health benefits including disease prevention. However, the action mechanisms of their activity remain poorly understood. Recent studies reported the effects of baicalein and betaine on cytotoxicity against colon cancer cells and chemically induced colitis-associated colon tumorigenesis in mice. Administrations of baicalein and betaine containing diets significantly inhibited the incidence of tumors and hyperplasia with down-regulation of inflammation. Therefore, baicalein and betaine might be applicable to the prevention of inflammation-associated colon carcinogenesis.
Related JoVE Video
A case of phacolytic glaucoma with anterior lens capsule disruption identified by scanning electron microscopy.
BMC Ophthalmol
PUBLISHED: 08-14-2014
Show Abstract
Hide Abstract
Phacolytic glaucoma is induced by lens protein or macrophages that have leaked through a macroscopically intact anterior lens capsule. Here, we report a case of phacolytic glaucoma with anterior lens capsule disruptions visualized by scanning electron microscopy (SEM).
Related JoVE Video
Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: a registry-based matched case-control study.
Circulation
PUBLISHED: 08-05-2014
Show Abstract
Hide Abstract
There is conflict regarding the prevalence of coronary artery disease (CAD) in patients with liver cirrhosis. This study aimed to investigate the prevalence of silent CAD in comparison with the general population, and to identify the relevant risk factors in patients with liver cirrhosis.
Related JoVE Video
Hemorrhagic Recurrence in Diffuse Astrocytoma without Malignant Transformation.
Brain Tumor Res Treat
PUBLISHED: 07-31-2014
Show Abstract
Hide Abstract
Although uncommon, hemorrhage can be a complication of low grade glioma with an unfavorable prognosis such as transformation to higher grade glioma. To our knowledge, hemorrhagic recurrence of World Health Organization Grade II, diffuse astrocytoma without malignant transformation has not been reported. Thus, we report a case of diffuse astrocytoma with hemorrhagic recurrence without malignant transformation. The patient had undergone craniotomy and tumor removal 7 years previously. Annual follow-up MRIs had shown evidence of slow tumor recurrence. With the sudden onset of seizure, the patient was diagnosed as hemorrhagic recurrence and underwent second tumor removal highly suspecting malignant change into higher grade glioma. Histopathology confirmed diffuse astrocytoma without malignant changes. As the patient's postoperative condition was excellent, we plan to withhold chemotherapy and radiation therapy for use as a later treatment option.
Related JoVE Video
Quantitative analysis of temperature dependent acoustic trapping characteristics by using concentric annular type dual element ultrasonic transducer.
Ultrasonics
PUBLISHED: 07-28-2014
Show Abstract
Hide Abstract
This paper presents the temperature dependence of lateral acoustic trapping capability by probing the speed of sound in individual lipid droplets at a given temperature of water and measuring its corresponding displacement, a value for quantitatively evaluating a spring-like behavior of the acoustic trap with certain strength. A 20/40MHz dual element LiNbO3 ultrasonic transducer is fabricated to simultaneously perform both transverse trapping and sound speed measurement for each droplet over a discrete temperature range from 20°C to 30°C. Time of flight method is employed for pulse tracking that determines the arrival time of an echo reflected back from either a trapped droplet or a mylar film. The estimated speeds of sound in water and droplets are 1484.8m/s and 1431.6m/s at 20°C, while 1506.0m/s and 1400.6m/s at 30°C, respectively. As the temperature rises, the sound speed in droplets decreases at an average rate of 3.1m/s/°C, and the speed in water increases at 2.1m/s/°C. The average displacement varies from 150.0?m to 179.0?m with an increasing rate of 2.9?m/°C, and its standard deviation is obtained between 1.0?m and 2.0?m over the same temperature range. Reduced sound speed as a function of rising temperature results in increased displacement, indicating that the trapping strength is adjustable by regulating ambient temperature in water as well as by changing transducer excitation parameters. Therefore, the results suggest that the temperature dependence of this trapping technique can be exploited for developing a remote manipulation tool of micron-sized particles in a thermally fluctuating environment. It is also shown that any deviated trapping strength caused by thermal disturbance near the trap can be restored to its desired level by compensating either temperature difference or trapping system condition.
Related JoVE Video
A phage protein that inhibits the bacterial ATPase required for type IV pilus assembly.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-21-2014
Show Abstract
Hide Abstract
Type IV pili (TFPs) are required for bacterial twitching motility and for phage infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as Tip, representing twitching inhibitory protein), whose expression is necessary and sufficient to mediate the inhibition of twitching motility. Tip interacts with and blocks the activity of bacterial-encoded PilB, the TFP assembly/extension ATPase, at an internal 40-aa region unique to PilB. Tip expression results in the loss of surface piliation. Based on these observations and the fact that many P. aeruginosa phages require TFPs for infection, Tip-mediated twitching inhibition may represent a generalized strategy for superinfection exclusion. Moreover, because TFPs are required for full virulence, PilB may be an attractive target for the development of novel antiinfectives.
Related JoVE Video
Chinese prescription Kangen-karyu and Salviae Miltiorrhizae Radix improve age-related oxidative stress and inflammatory response through the PI3K/Akt or MAPK pathways.
Am. J. Chin. Med.
PUBLISHED: 07-10-2014
Show Abstract
Hide Abstract
This study examined whether Kangen-karyu and its crude drug, Salviae Miltiorrhizae Radix, have a reno-protective effect on the age-related oxidative stress and inflammatory response through the phosphoinositide 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK) pathways in aged rats. Kangen-karyu or Salviae Miltiorrhizae Radix (20 mg/kg body weight/day) was administered orally to old groups of rats for 16 days, and their effects were compared with the vehicle-treated old and young rats. The administration of Kangen-karyu caused a slight decrease in the serum glucose level and a significant decrease in the serum insulin level in the old rats. The increased levels of serum renal functional parameter (urea-nitrogen) and oxidative parameter were significantly reduced by both Kangen-karyu and Salviae Miltiorrhizae Radix. The old rats exhibited a dysregulation of the protein expression related to insulin resistance, oxidative stress, and inflammation in the kidneys, but Kangen-karyu administration significantly reduced the expression of the inflammatory proteins through the PI3K/Akt pathway. On the other hand, the Salviae Miltiorrhizae Radix-treated old rats showed a decrease in the inflammatory cytokines through the MAPK pathway. These results provide important evidence that Kangen-karyu and Salviae Miltiorrhizae Radix have a pleiotropic effect on the PI3K/Akt and MAPK pathways, showing renoprotective effects against the development of inflammation in old rats. This study provides scientific evidence that Kangen-karyu and Salviae Miltiorrhizae Radix improve the inflammatory responses via the PI3K/Akt or MAPK pathways in the kidney of old rats.
Related JoVE Video
Effectiveness of the smart care service for diabetes management.
Healthc Inform Res
PUBLISHED: 07-02-2014
Show Abstract
Hide Abstract
The aim of this study was to assess the effectiveness of the Smart Care service for the diabetes management.
Related JoVE Video
Sphingosine 1-phosphate induced anti-atherogenic and atheroprotective M2 macrophage polarization through IL-4.
Cell. Signal.
PUBLISHED: 06-26-2014
Show Abstract
Hide Abstract
Sphingosine 1-phosphate (S1P) has been implicated in anti-atherogenic properties of high-density lipoproteins. However, the roles and signaling of S1P in macrophages, the main contributor to atherosclerosis, have not been well studied. Furthermore, pro-inflammatory M1 and anti-inflammatory M2 macrophage phenotypes may influence the development of atherosclerosis. Therefore, we investigated the effects of S1P on macrophage phenotypes, especially on M2 polarization and its signaling in relation to the anti-atherogenic properties of S1P. It was found that S1P induced anti-inflammatory M2 polarization via IL-4 secretion and its signaling, and induced IL-4R? and IL-2R?. In addition, down-stream signalings, such as, stat-6 phosphorylation, SOCS1 induction, and SOCS3 suppression were also observed in macrophages in response to S1P. Furthermore, S1P-induced ERK activation, and the inhibitions of p38 MAPK and JNK were found to be key signals for IL-4 induction. Moreover, the anti-atherogenic effect of S1P in HDL was confirmed by the observation that oxidized LDL-induced lipid accumulation was attenuated in S1P-treated M2 macrophages. Furthermore, the atheroprotective effect of S1P was demonstrated by its anti-apoptotic effect on S1P-treated macrophages. The present study shows that S1P-induced M2 polarization of macrophages could be mediated via IL-4 signaling, and suggests that M2 polarization by S1P is responsible for the anti-atherogenic and atheroprotective properties of high-density lipoproteins in vivo.
Related JoVE Video
Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system.
Pharmacol. Rev.
PUBLISHED: 06-25-2014
Show Abstract
Hide Abstract
During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-?B, hypoxia-inducible factor 1?, peroxisome proliferator-activated receptor ?, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied.
Related JoVE Video
Preliminary study of neurocognitive dysfunction in adult moyamoya disease and improvement after superficial temporal artery-middle cerebral artery bypass.
J Korean Neurosurg Soc
PUBLISHED: 05-13-2014
Show Abstract
Hide Abstract
Moyamoya disease (MMD) is a chronic cerebrovascular occlusive disease of unknown etiology. In addition, the neurocognitive impairment of adults with MMD is infrequently reported and, to date, has not been well described. We attempted to determine both the neurocognitive profile of adult moyamoya disease and whether a superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis can improve the neurocognitive impairment in exhibiting hemodynamic disturbance without stroke.
Related JoVE Video
Age-related inflammation and insulin resistance: a review of their intricate interdependency.
Arch. Pharm. Res.
PUBLISHED: 04-16-2014
Show Abstract
Hide Abstract
Chronic inflammation is a major risk factor underlying aging and the associated diseases of aging; of particular interest is insulin resistance during aging. Chronic inflammation impairs normal lipid accumulation, adipose tissue function, mitochondrial function, and causes endoplasmic reticulum (ER) stress, which lead to insulin resistance. However, some studies show that insulin resistance itself amplifies chronic inflammation. The activity of the insulin-dependent Akt signaling pathway is highlighted because of its decrease in insulin-sensitive organs, like liver and muscle, which may underlie insulin resistance and hyperinsulinemia, and its increased levels in non-metabolic organs, such as kidney and aorta. In that the prevalence of obesity has increased substantially for all age groups in recent years, our review summarizes the data showing the involvement of chronic inflammation in obesity-induced insulin resistance, which perpetuates reciprocal interactions between the chronic inflammatory process and increased adiposity, thereby accelerating the aging process.
Related JoVE Video
Anti-inflammatory effects of betaine on AOM/DSS?induced colon tumorigenesis in ICR male mice.
Int. J. Oncol.
PUBLISHED: 04-14-2014
Show Abstract
Hide Abstract
Betaine is an important human nutrient obtained from various foods and studies in animals and humans have provided results suggesting their pathogenesis of various chronic diseases and points to a role in risk assessment and disease prevention. However, the molecular mechanisms of its activity remain poorly understood and warrant further investigation. This study was performed to investigate the anti-inflammation and tumor preventing capacity of betaine on colitis-associated cancer in mice. In in vivo experiments, we induced colon tumors in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS) and evaluated the effects of betaine on tumor growth. Administration with betaine significantly decreased the incidence of tumor formation with downregulation of inflammation. Treatment with betaine inhibited ROS generation and GSSG concentration in colonic mucosa. Based on the qPCR data, administration of betaine inhibited inflammatory cytokines such TNF-?, IL-6, iNOS and COX-2. In in vitro experiments, LPS-induced NF-?B and inflammatory-related cytokines were inhibited by betaine treatment in RAW 264.7 murine macrophage cells. Our findings suggest that betaine is one of the candidates for the prevention of inflammation-associated colon carcinogenesis.
Related JoVE Video
Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress.
Eur. J. Pharmacol.
PUBLISHED: 04-05-2014
Show Abstract
Hide Abstract
Since it has been known that shikonin derived from a medicinal plant possesses anti-cancer activity, we wonder whether acetylshikonin (ASK), a derivate of shikonin, can be used to treat hepatocellular carcinoma cells expressing hepatitis B virus X protein (HBX), an oncoprotein from hepatitis B virus. When ASK was added to Hep3B cells stably expressing HBX, it induced apoptosis in a dose-dependent manner. ASK induced upregulation and export of Nur77 to the cytoplasm and activation of JNK. Likewise, suppression of Nur77 and JNK inactivation protected the cells from ASK-induced apoptosis, indicating that Nur77 upregulation and JNK activation were required for ASK-mediated apoptosis. Furthermore, ASK increased the expression of Bip and ubiquitination levels of cellular proteins, features of endoplasmic reticulum (ER) stress, via the production of reactive oxygen species in a dose-dependent manner. Suppression of reactive oxygen species with N-acetylcysteine reduced levels of Bip protein and ubiquitination levels of cellular proteins during ASK treatment, leading to protection of cells from apoptosis. Cycloheximide treatment reduced ASK-induced ER stress, suggesting that protein synthesis is involved in ASK-induced ER stress. Moreover, we showed using salubrinal, an ER stress inhibitor that reactive oxygen species production, JNK activation, and Nur77 upregulation and its translocation to cytoplasm are necessary for ER-induced stress. Interestingly, we found that JNK inactivation suppresses ASK-induced ER stress, whereas Nur77 siRNA treatment does not, indicating that JNK is required for ASK-induced ER stress. Accordingly, we report that ASK induces ER stress, which is prerequisite for apoptosis of HBX-expressing hepatocellular carcinoma cells.
Related JoVE Video
Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice.
Aging Cell
PUBLISHED: 03-23-2014
Show Abstract
Hide Abstract
The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2 mg kg(-1) day(-1) ) was administered orally for 5 months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated ?-galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the I?B? and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound.
Related JoVE Video
Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type.
Psychiatry Clin. Neurosci.
PUBLISHED: 03-19-2014
Show Abstract
Hide Abstract
An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH).
Related JoVE Video
Genome-wide transcriptional sequencing identifies novel mutations in metabolic genes in human hepatocellular carcinoma.
Cancer Genomics Proteomics
PUBLISHED: 03-18-2014
Show Abstract
Hide Abstract
We report on next-generation transcriptome sequencing results of three human hepatocellular carcinoma tumor/tumor-adjacent pairs. This analysis robustly examined ?12,000 genes for both expression differences and molecular alterations. We observed 4,513 and 1,182 genes demonstrating 2-fold or greater increase or decrease in expression relative to their normal, respectively. Network analysis of expression data identified the Aurora B signaling, FOXM1 transcription factor network and Wnt signaling pathways pairs being altered in HCC. We validated as differential gene expression findings in a large data set containing of 434 liver normal/tumor sample pairs. In addition to known driver mutations in TP53 and CTNNB1, our mutation analysis identified non-synonymous mutations in genes implicated in metabolic diseases, i.e. diabetes and obesity: IRS1, HMGCS1, ATP8B1, PRMT6 and CLU, suggesting a common molecular etiology for HCC of alternative pathogenic origin.
Related JoVE Video
Sutureless intrascleral pocket technique of transscleral fixation of intraocular lens in previous vitrectomized eyes.
Korean J Ophthalmol
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
In this case series, we assessed a new technique, the intrascleral pocket procedure of transscleral fixation (TF) of the intraocular lens (IOL) in post-vitrectomized eyes. We performed the transscleral fixation of IOL in four aphakic patients who underwent pars plana vitrectomy. Two points 180° apart were marked at the limbus. A 2-mm-sized intrascleral pocket was created by lamellar dissection using a crescent blade without conjunctival dissection. A 2.8-mm clear corneal incision (CCI) was made using a keratome. Prolene sutures were exteriorized through the CCI pocket and a three-piece foldable acrylic IOL was injected via CCI and the ends of the haptics were exteriorized through the CCI. The prolene sutures for each haptic in the intrascleral pocket bed were then tied and knots were buried under scleral flaps. No patient had complaints such as conjunctival irritation, and visual acuity was almost identical to preoperative best-corrected visual acuity at day 1 postoperatively. IOLs were well placed without tilting or subluxation. They had no wound dehiscence or endophthalmitis postoperatively. The intrascleral pocket procedure of TF without the need for conjunctival dissection is a successful method for sulcus fixation in post-vitrectomized eyes predisposed to developing glaucoma.
Related JoVE Video
A key role for neuropeptide Y in lifespan extension and cancer suppression via dietary restriction.
Sci Rep
PUBLISHED: 03-13-2014
Show Abstract
Hide Abstract
Knowledge of genes essential for the life-extending effect of dietary restriction (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy), which mediates physiological adaptations to energy deficits, is an essential link between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30% DR was attenuated in Npy-null mice, as was the effect on the occurrence of spontaneous tumors and oxidative stress responses in comparison to wild-type mice. In contrast, the physiological processes activated during adaptation to DR, including inhibition of anabolic signaling molecules (insulin and insulin-like growth factor-1), modulation of adipokine and corticosterone levels, and preferential fatty acid oxidation, were unaffected by the absence of Npy. These results suggest a key role for Npy in mediating the effects of DR. We also provide evidence that most of the physiological adaptations to DR could be achieved in mice without Npy.
Related JoVE Video
The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial.
Int. J. Cancer
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ?3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.
Related JoVE Video
The essential role of FoxO6 phosphorylation in aging and calorie restriction.
Age (Dordr)
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Changes in the activities of FoxOs caused by phosphorylation, acetylation, or ubiquitination induce expressional changes in the genes involved in the modulation of oxidative stress by modifying histones and chromatins and can substantially alter cellular functions during aging and age-related diseases. However, the precise role that FoxO6, a novel member of the FoxO class of transcription factors, plays in the aging kidney has not been determined. The purpose of this study was to determine the role played by FoxO6 in the maintenance of redox homeostasis in HEK293T cells and aged kidney tissues isolated from ad libitum (AL)-fed and 40 % calorie restriction (CR) rats. The results obtained from AL-fed rats showed that diminished FoxO6 activity during aging was caused by FoxO6 phosphorylation, which disabled its transcriptional activity. In contrast, CR rats were found to have significantly higher FoxO6 activities and maintained redox balance. To determine the molecular mechanism responsible for FoxO6 modification by age-related oxidative stress, we examined H2O2-treated HEK293T cells in which FoxO6 was inactivated by phosphorylation and found that H2O2-induced oxidative stress promoted FoxO6 phosphorylation via PI3K/Akt signaling. The results of this study show that the protective role of FoxO6 in the aging process may in part be related to its ability to attenuate oxidative stress by upregulating catalase expression, as shown in CR. This delineation of the role of FoxO6 expands understanding of the pathological and physiological mechanisms of aging.
Related JoVE Video
A Pilot Study for Discovering Candidate Genes of Chromosome 18q21 in Methamphetamine Abusers: Case-control Association Study.
Clin Psychopharmacol Neurosci
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
It was previously suggested that the malic enzyme 2 (ME2) as the candidate gene for psychosis in fine mapping of chromosome 18q21. Chromosome 18q21 is also one of the possible regions that can contribute to addiction.
Related JoVE Video
Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells.
Int. J. Oncol.
PUBLISHED: 02-24-2014
Show Abstract
Hide Abstract
Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid, shown to have chemopreventive and/or anticancer properties in a variety of human cancer cells. The involvement of autophagy in apigenin-induced apoptotic cell death of HCT116 human colon cancer cells was investigated. Apigenin induced suppression of cell growth in a concentration-dependent manner in HCT116 cells. Flow cytometric analyses indicated that apigenin resulted in G2/M phase arrest. This flavone also suppressed the expression of both cyclin B1 and its activating partners, Cdc2 and Cdc25c, whereas the expression of cell cycle inhibitors, such as p53 and p53-dependent p21(CIP1/WAF1), was increased after apigenin treatment. Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles by flow cytometry. Furthermore, the results of the western blot analysis revealed that the levels of LC3-II, the processed form of LC3-I, was increased by apigenin. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the levels of PARP cleavage. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in HCT116 colon cancer cells. Autophagy plays a cytoprotective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for colon cancer control.
Related JoVE Video
Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APC-mutated colon cancer cells through promotion of ?-catenin degradation.
Food Chem. Toxicol.
PUBLISHED: 02-03-2014
Show Abstract
Hide Abstract
Ursolic acid (UA) and corosolic acid (CA), naturally occurring pentacyclic triterpene acids, exhibit antiproliferative activities against various cancer cells, but a clear chemopreventive mechanism of these triterpenoids in colon cancer cells remains to be answered. Here we used a cell-based reporter system for detection of ?-catenin response transcription (CRT) to identify UA as an antagonist of the Wnt/?-catenin pathway. UA promoted the degradation of intracellular ?-catenin that was accompanied by its N-terminal phosphorylation at Ser33/37/Thr41 residues, marking it for proteasomal degradation. Consistently, UA down-regulated the intracellular ?-catenin level in colon cancer cells with inactivating mutations of adenomatous polyposis coli (APC). In addition, UA repressed the expression of ?-catenin/T-cell factor (TCF)-dependent genes, thereby inhibiting cell proliferation in colon cancer cells. The functional group analysis revealed that the major structural requirements for UA-mediated ?-catenin degradation are a carboxyl group at position 17 and a methyl group at position 19. Notably, CA (2?-hydroxyursolic acid) was also found to decrease the level of intracellular ?-catenin and to suppress the growth of APC-mutated colon cancer cells. Our findings suggest that UA and CA exert their anticancer activities against colon cancer cells by promoting the N-terminal phosphorylation and subsequent proteasomal degradation of ?-catenin.
Related JoVE Video
Feroniellin A-induced autophagy causes apoptosis in multidrug-resistant human A549 lung cancer cells.
Int. J. Oncol.
PUBLISHED: 01-30-2014
Show Abstract
Hide Abstract
During the screening of natural chemicals that can reverse multidrug resistance in human A549 lung cancer cells resistant to etoposide (A549RT-eto), we discovered that Feroniellin A (FERO), a novel furanocoumarin, shows toxicity toward A549RT-eto cells in a dose- and time-dependent manner. FERO reduced the expression of NF-?B, leading to downregulation of P-glycoprotein (P-gp), encoded by MDR1, which eventually sensitized A549RT-eto cells to apoptosis. FERO specifically diminished transcription and promoter activity of MDR1 but did not inhibit the expression of other multidrug resistance genes MRP2 and BCRP. Moreover, co-administration of FERO with Bay11-7802, an inhibitor of NF-?B, accelerated apoptosis of A549RT-eto cells through decreased expression of P-gp, indicating that NF-?B is involved in multidrug resistance. Conversely, addition of Z-VAD, a pan-caspase inhibitor, blocked FERO-induced apoptosis in A549RT-eto cells but did not block downregulation of P-gp, indicating that a decrease in P-gp expression is necessary but not sufficient for FERO-induced apoptosis. Interestingly, we found that FERO also induces autophagy, which is characterized by the conversion of LC3 I to LC3 II, induction of GFP-LC3 puncta, enhanced expression of Beclin-1 and ATG5, and inactivation of mTOR. Furthermore, suppression of Beclin-1 by siRNA reduced FERO-induced apoptosis in A549RT-eto cells and activation of autophagy by rapamycin accelerated FERO-induced apoptosis, suggesting that autophagy plays an active role in FERO-induced apoptosis. Herein, we report that FERO reverses multidrug resistance in A549RT-eto cells and exerts its cytotoxic effect by induction of both autophagy and apoptosis, which suggests that FERO can be a useful anticancer drug for multidrug-resistant lung cancer.
Related JoVE Video
Role of 15-hydroxyprostaglandin dehydrogenase down-regulation on the prognosis of hepatocellular carcinoma.
Clin Mol Hepatol
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
The role of prostaglandin E2 (PGE2) in the modulation of cell growth is well established in colorectal cancer. The aim of this study was to elucidate the significance of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) down-regulation on the prognosis of hepatocellular carcinoma (HCC) patients.
Related JoVE Video
The effect of 0.02% mitomycin C injection into the hair follicle with radiofrequency ablation in trichiasis patients.
Korean J Ophthalmol
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
To investigate the inhibitory effect of 0.02% mitomycin C on eyelash regrowth when injected to the eyelash hair follicle immediately after radiofrequency ablation.
Related JoVE Video
Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis.
Int. J. Oncol.
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
We showed in our previous study that cancer upregulated gene (CUG) 2, a novel oncogene, confers resistance to infection of oncolytic vesicular stomatitis virus (VSV) by activating Stat1-mediated signal transduction. Since many studies have reported that autophagy is involved in virus replication, we investigated whether autophagy also plays a role in the antiviral activity in A549 cells overexpressing CUG2 (A549-CUG2). We suppressed Atg5 or Beclin 1 expression using siRNA and examined its effect on the susceptibility of cells to infection by oncolytic VSV. We found that A549-CUG2 cells treated with Atg5 or Beclin 1 siRNA became susceptible to VSV infection, whereas A549-CUG2 cells treated with control siRNA were resistant. This result suggests that autophagy is involved in the antiviral response of A549-CUG2 cells. Further investigation revealed that autophagy impairment enhanced the generation of reactive oxygen species (ROS), which resulted in inactivation of S6 kinase. Under these conditions, the levels of ISG15 transcript and protein decreased, which conferred on A549-CUG2 cell susceptibility to VSV infection. Finally, we found that overloading of H?O? sensitized control A549-CUG2 cells to VSV-induced apoptosis. Taken together, these results indicate that autophagy impairment induces excessive ROS formation, which decreases S6 kinase activity and ISG15 expression, ultimately rendering the A549-CUG2 cells susceptible to VSV infection. We propose that autophagy impairment is a potential strategy for successful VSV virotherapy of CUG2-overexpressing tumors.
Related JoVE Video
MHY884, a newly synthesized tyrosinase inhibitor, suppresses UVB-induced activation of NF-?B signaling pathway through the downregulation of oxidative stress.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-16-2014
Show Abstract
Hide Abstract
The skin is the primary target of prolonged and repeated ultraviolet (UVB) irradiation which induces cutaneous inflammation and pigmentation. Nuclear factor ?B (NF-?B) is the major factor mediating UVB-induced inflammatory responses through the expression of various proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We have previously reported that the synthetic novel compound 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol (MHY884) strongly suppressed tyrosinase activity and melanin synthesis in B16F10 melanoma cells. In the present study, we investigated the effect of MHY884 on the inhibition of UVB-induced NF-?B activation and its proinflammatory downstream proteins through the suppression of oxidative stress in an in vivo model of photoaging. Generation of reactive oxygen species (ROS) and peroxynitrite was measured in vitro and in B16F10 melanoma cells to verify the scavenging activity of MHY884. MHY884 suppressed oxidative stress both in vitro and in the melanoma cells in a dose-dependent manner. Next, melanin-possessing hairless mice were pre-treated with MHY884 and then irradiated with UVB repeatedly. Topical application of MHY884 attenuated UVB-induced oxidative stress, resulting in reduced NF-?B activity. Pre-treatment with MHY884 inhibited Akt and I?B kinase ?/? signaling pathways, leading to decreased translocation and phosphorylation of p65, a subunit of NF-?B. This result correlated with the expression levels of iNOS and COX-2 in the skin of MHY884-treated mice. Thus, the novel tyrosinase inhibitor MHY884 suppressed NF-?B activation signaling pathway by scavenging UVB-induced oxidative stress. The discovery of MHY884, a novel tyrosinase inhibitor that targets NF-?B signaling, is significant, because this compound is a promising protective agent against UVB-induced skin damage.
Related JoVE Video
Synthesis of PPAR-? activators inspired by the marine natural product, paecilocin A.
Mar Drugs
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-? agonist) and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 3-14. Compound 7 showed significant PPAR-? activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-? activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-? with EC50 values of 0.67 ?M and 0.028 ?M, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-? ligands.
Related JoVE Video
Superinfection exclusion reveals heteroimmunity between Pseudomonas aeruginosa temperate phages.
J. Microbiol.
PUBLISHED: 01-07-2014
Show Abstract
Hide Abstract
Temperate siphophages (MP29, MP42, and MP48) were isolated from the culture supernatant of clinical Pseudomonas aeruginosa isolates. The complete nucleotide sequences and annotation of the phage genomes revealed the overall synteny to the known temperate P. aeruginosa phages such as MP22, D3112, and DMS3. Genome-level sequence analysis showed the conservation of both ends of the linear genome and the divergence at the previously identified dissimilarity regions (R1 to R9). Protein sequence alignment of the c repressor (ORF1) of each phage enabled us to divide the six phages into two groups: D3112 group (D3112, MP29, MP42, and MP48) and MP22 group (MP22 and DMS3). Superinfection exclusion was observed between the phages belonging to the same group, which was mediated by the specific interaction between the c repressor and the cognate operator. Based on these, we suggest that the temperate siphophages prevalent in the clinical strains of P. aeruginosa represent at least two distinct heteroimmunity groups.
Related JoVE Video
IFITM3 Polymorphism rs12252-C Restricts Influenza A Viruses.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The IFITM3 polymorphism rs12252-C, which encodes an IFITM3 isoform (?21 IFITM3) lacking 21 amino acids at the amino terminus, has been controversially associated with poor clinical outcomes in patients with H1N1 influenza A virus (IAV) infections. In vitro studies have shown that ?21 IFITM3 loses its ability to restrict H1N1 IAV. Subsequent research has also revealed that tyrosine 20 is the key determinant for IFITM3 endocytic trafficking, which is essential for the efficient anti-viral activity of IFITM3. In contrast to previous studies, we demonstrated that both ?21 IFITM3 and an IFITM3 variant (Y20A IFITM3), in which tyrosine 20 is substituted with alanine, strongly restricted entry mediated by IAV H1, H3, H5, and H7 proteins. ?21 IFITM3 also efficiently suppressed replication of H1N1 and, to a lesser extent, H3N2 IAV. ?21 IFITM3 and Y20A IFITM3 had broader subcellular distributions than full-length IFITM3 but an abundant amount of both IFITM3 variants still localized to late endosomes and lysosomes. Our data indicate that tyrosine 20 partially regulates the subcellular localization of IFITM3 but is not functionally essential for IFITM3-mediated IAV restriction. They also suggested that mechanisms, other than viral entry restriction, might contribute to variations in clinical outcomes of H1N1 influenza associated with rs12252-C.
Related JoVE Video
Anti-wrinkle effect of magnesium lithospermate B from Salvia miltiorrhiza BUNGE: inhibition of MMPs via NF-kB signaling.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Skin is in direct contact with the environment and therefore undergoes aging as a consequence of environmentally induce damage. Wrinkle formation is a striking feature of intrinsic and photo-induced skin aging, which are both associated with oxidative stress and inflammatory response. The present study was undertaken to identify the mechanisms responsible for the anti-wrinkle effects of MLB, and thus, we investigated whether magnesium lithospermate B (MLB) from Salvia miltiorrhiza BUNGE associated with wrinkle formation caused by intrinsic and extrinsic skin aging using Sprague-Dawley rats aged 5 and 20 months and ultraviolet B (UVB)-irradiated human skin fibroblasts cells, respectively. The results obtained showed that the oral administration of MLB significantly upregulated the level of type I procollagen and downregulated the activities and expressions of matrix-metalloproteinases (MMPs) in rat skin. In fibroblasts, MLB suppressed the transactivation of nuclear factor-kB (NF-kB) and activator protein 1(AP-1), which are the two transcription factors responsible for MMP expression, by suppressing oxidative stress and the mitogen activated protein kinase (MAPK) pathway. Our results show that the antioxidant effect of MLB is due to the direct scavenging of reactive oxygen species (ROS) and its inhibitory effects on NF-kB-dependent inflammation genes, such as, cyclooxygenase-2 and inducible nitric oxide synthase. MLB was found to reverse both age- and UVB-related reductions in skin procollagen levels by suppressing the expressions and activities of NF-kB and AP-1-dependent MMPs by modulating ROS generation and the MAPK signaling pathway. We suggest that MLB potentially has anti-wrinkle and anti-skin aging effects.
Related JoVE Video
?-Hydroxy ?-methylbutyrate improves dexamethasone-induced muscle atrophy by modulating the muscle degradation pathway in SD rat.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and ?-hydroxy ?-methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy.
Related JoVE Video
HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability.
Gut
PUBLISHED: 10-25-2013
Show Abstract
Hide Abstract
Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB).
Related JoVE Video
A novel oxiranylchromenone derivative, MHY336, induces apoptosis and cell cycle arrest via a p53- and p21-dependent pathway in HCT116 human colon cancer cells.
Int. J. Oncol.
PUBLISHED: 10-18-2013
Show Abstract
Hide Abstract
In this study, we compared cytotoxicity, cell cycle distribution, and apoptosis on MHY336 treatment in three human colorectal carcinoma HCT116 cells: p53+/+ (p53?wt), p53-/- (p53-null), and p21-/- (p21-null), as well as investigated the roles of p53 and p21 in cell death. Using these three isogenic variants, the roles of p53 and p21 in the cellular response to treatment with MHY336, a novel topoisomerase II? inhibitor, were investigated. Our results showed that MHY336 treatment increased the expression of p53 over time in cells with wild-type p53 status. This elevated levels of p53 is associated with increased DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase, consistent with increased sensitivity of these cells to apoptotic stimuli. However, p53-null and p21-null cells were more resistant to the antiproliferative and apoptotic effects of MHY336 than p53-wt cells. The same result was achieved by knocking down p53 and p21 with siRNA in p53-wt cells, indicating that p53 and p21 play a crucial role in MHY336-induced cell cycle arrest and apoptosis. Taken together, these results suggest that MHY336 could be a potential candidate to be used in chemoprevention and/or treatment of colon cancer.
Related JoVE Video
Extract of Bryophyllum laetivirens reverses etoposide resistance in human lung A549 cancer cells by downregulation of NF-?B.
Oncol. Rep.
PUBLISHED: 10-02-2013
Show Abstract
Hide Abstract
Since multidrug resistance (MDR) is one of the main reasons for failure in cancer treatment, its suppression may increase the efficacy of cancer therapy. In the present study we attempted to identify a new and effective anticancer drug against MDR cancer cells. We first found that lung cancer A549 cells resistant to etoposide (A549RT-eto) exhibit upregulation of NF-?B and SIRT1 in comparison to A549 parental cells. During a search for anticancer drug candidates from medicinal plant sources, we found that an extract fraction (F14) of Bryophyllum laetivirens leaves downregulated expression of NF-?B and SIRT1, sensitizing the levels of A549RT-eto cells to apoptosis through downregulation of P-glycoprotein (P-gp), which is encoded by the MDR1 gene. To address whether NF-?B is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with Bay11-7802, an inhibitor of NF-?B. We then observed that Bay11-7802 treatment reduced P-gp expression levels, and furthermore combined treatment with the F14 extract and Bay11-7802 accelerated apoptosis through a decrease in P-gp levels, suggesting that NF-?B is involved in MDR. To address whether upregulation of SIRT1 is involved in resistance to etoposide through P-gp, we treated A549RT-eto cells with SIRT1 siRNA or nicotinamide (NAM), an inhibitor of SIRT1. we found that suppression of SIRT1 did not reduce P-gp levels. furthermore, the combined treatment with the F14 extract, and SIRT1 siRNA or NAM did not accelerate apoptosis, indicating that SIRT1 is not involved in the regulation of P-gp levels in A549RT-eto cells. Taken together, we suggest that upregulation of NF-?B determines etoposide resistance through P-gp expression in human A549 lung cancer cells. We herein demonstrated that B. laetivirens extract reverses etoposide resistance in human A549 lung cancer cells through downregulation of NF-?B.
Related JoVE Video
HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells.
Int. J. Oncol.
PUBLISHED: 08-29-2013
Show Abstract
Hide Abstract
Resveratrol, a polyphenolic compound, is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. It has gained much attention for its potential anticancer activity against various types of human cancer. However, the usefulness of resveratrol as a chemotherapeutic agent is limited by its photosensitivity and metabolic instability. In this study the effects of a synthetic analogue of resveratrol, HS-1793, on the proliferation and apoptotic cell death were investigated using MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) human breast cancer cells. HS-1793 inhibited cell growth and induced apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was determined by morphological changes, cleavage of poly(ADP-ribose) poly-merase, alteration of Bax/Bcl-2 expression ratio and caspase activities. Flow cytometric analysis revealed that HS-1793 induced G2/M arrest in the cell cycle progression in both types of cells. Of note, HS-1793 induced p53/p21WAF1/CIP1-dependent apoptosis in MCF-7 cells, whereas it exhibited p53-independent apoptosis in MDA-MB-231 cells. Furthermore, HS-1793 showed more potent anticancer effects in several aspects compared to resveratrol in MCF-7 and MDA-MB-231 cells. Thus, these findings suggest that HS-1793 has potential as a candidate chemotherapeutic agent against human breast cancer.
Related JoVE Video
Common virulence factors for Pseudomonas tolaasii pathogenesis in Agaricus and Arabidopsis.
Res. Microbiol.
PUBLISHED: 08-18-2013
Show Abstract
Hide Abstract
Brown blotch of cultivatable mushrooms is a disease caused by the small peptide toxin (tolaasin) secreted by Pseudomonas tolaasii. Here we found that the wild type tolassin-producing P. tolaasii stain 6264 was capable of infection in Arabidopsis thaliana cotyledons, causing chlorotic symptoms and growth arrest as a result of bacterial proliferation. Seven virulence-attenuated mutants of P. tolaasii were isolated from the Agaricus bisporous screen using 2,512 mariner-based transposon insertion mutants, and all of them displayed reduced virulence and bacterial proliferation in Arabidopsis infection as well. The transposon was inserted within the genes for tolassin biosynthesis and amino acid biosynthesis, and within an intergenic region between the genes of unknown function. The finding that some virulence factors are commonly required for both Agaricus and Arabidopsis infections suggests that Arabidopsis could be exploited to study the host-pathogen interaction involving P. tolaasii.
Related JoVE Video
A novel hydroxamic acid derivative, MHY218, induces apoptosis and cell cycle arrest through downregulation of NF-?B in HCT116 human colon cancer cells.
Int. J. Oncol.
PUBLISHED: 07-22-2013
Show Abstract
Hide Abstract
Colorectal cancer (CRC) is one of the most common malignant diseases and frequent cause of cancer deaths in the world. In spite of the significant advances in conventional therapeutic approaches to CRC, most patients ultimately die of their disease. There is a need to develop novel preventive approaches for this malignancy. This study was carried out to investigate the anticancer effect of MHY218, a hydroxamic acid derivative, in HCT116 human colon cancer cells. Treatment of cells with MHY218 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner. MHY218 induced G2/M phase arrest in the cell cycle progression which was observed by flow cytometry analysis, and a decrease in the protein expression of cyclin B1 and its activating partners Cdc25C and Cdc2. MHY218 also caused an increase in the expression levels of p21WAF1/CIP1, a G2/M phase inhibitor, in a p53-independent pathway. The induction of apoptosis was observed by decreased viability, DNA fragmentation, cleavage of poly(ADP-ribose) polymerase, alteration in the ratio of Bax/Bcl-2 protein expression, and activation of caspase-3, -8 and -9. In addition, MHY218 treatment showed downregulation of the expression levels of the transcription factor nuclear factor-kappa B (NF-?B) in the nucleus, which has been reported to be implicated in the apoptotic cell death of several types of cancer cells, suppression of TNF-?-induced NF-?B activation, inhibition of cyclooxygenase-2 expression, repression of matrix metalloproteinase-9 activation and decrease of 5-lipoxygenase in a concentration-dependent manner. These results suggest that MHY218 may be a useful candidate to be used in the chemoprevention and/or treatment of colon cancer.
Related JoVE Video
A novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1? and VEGF expression, and migration in human prostate cancer cells.
Int. J. Oncol.
PUBLISHED: 07-14-2013
Show Abstract
Hide Abstract
In many studies, resveratrol has been shown to have a chemopreventive effect in various types of cancer cells. However, the biological activity of resveratrol is limited by its photosensitivity and metabolic instability. This study investigated the effects of a novel analogue of resveratrol, HS-1793, on the expression of HIF-1? and vascular endothelial growth factor (VEGF) in PC-3 human prostate cancer cells. Hypoxic condition induced HIF-1? protein level in PC-3 cells in a time-dependent manner, and treatment with HS-1793 markedly decreased HIF-1? expression levels. HS-1793 also inhibited VEGF level. Mechanistically, HS-1793 inhibited HIF-1? and VEGF expression through multiple mechanisms. Firstly, HS-1793 inhibited phosphorylation of PI3K and Akt in PC-3 cells. Furthermore, HS-1793 substantially induced HIF-1? protein degradation through the proteasome pathway. Finally, HS-1793 inhibited hypoxia-induced PC-3 cell migration. These data suggest that HS-1793 may inhibit human prostate cancer progression and angiogenesis by inhibiting the expression of HIF-1? and VEGF. Moreover, HS-1793 showed more potent effects than resveratrol on the cytotoxic effects on PC-3 cells. Taken together, these results implied that HS-1793, a novel analogue of resveratrol, may be a new potent chemopreventive agent against human prostate cancer cells.
Related JoVE Video
Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice.
Int. J. Oncol.
PUBLISHED: 07-09-2013
Show Abstract
Hide Abstract
Flavonoids have been demonstrated to provide health benefits in humans. Baicalein (5,6,7-trihydroxyflavone) is a phenolic flavonoid compound derived mainly from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in oriental medicine. Baicalein is widely used in Korean and Chinese herbal medicines as anti-inflammatory and anticancer therapy. However, the molecular mechanisms of its activity remain poorly understood and warrant further investigation. This study was performed to investigate the anticancer effect of baicalein on HCT116 human colon cancer cells and the tumor preventing capacity of baicalein on colitis-associated cancer in mice. In in vivo experiments, we induced colon tumors in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS) and evaluated the effects of baicalein on tumor growth. Baicalein treatment on HCT116 cells resulted in a concentration-dependent inhibition of cell growth and induction of apoptotic cell death. The induction of apoptosis was determined by morphological changes and cleavage of poly(ADP-ribose) polymerase. Baicalein also suppressed the activation of NF-?B through PPAR? activation. These results indicate that the anti-inflammatory effects of baicalein may be mediated through PPAR? activation. Finally, administration with baicalein significantly decreased the incidence of tumor formation with inflammation. Our findings suggest that baicalein is one of the candidates for the prevention of inflammation-associated colon carcinogenesis.
Related JoVE Video
Two indices affecting the directions of the sylvian fissure dissection in middle cerebral artery bifurcation aneurysms.
J Cerebrovasc Endovasc Neurosurg
PUBLISHED: 07-05-2013
Show Abstract
Hide Abstract
This study proposes more objective methods for deciding the appropriate direction of the sylvian fissure dissection during surgical clipping in middle cerebral artery (MCA) bifurcation aneurysms.
Related JoVE Video
The usefulness of the ivy sign on fluid-attenuated intensity recovery images in improved brain hemodynamic changes after superficial temporal artery-middle cerebral artery anastomosis in adult patients with moyamoya disease.
J Korean Neurosurg Soc
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
MR perfusion and single photon emission computerized tomography (SPECT) are well known imaging studies to evaluate hemodynamic change between prior to and following superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated inversion recovery (FLAIR) images in adult patients with moyamoya disease and compared it with result of SPECT and MR perfusion images.
Related JoVE Video
Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-?B in LPS-stimulated RAW264.7 cells and mouse liver.
J Ginseng Res
PUBLISHED: 05-30-2013
Show Abstract
Hide Abstract
Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-?B activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) PGE2 synthesis (69% to 93% inhibition); 3) NF-?B activity; and 4) the NF-?B-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-?B and the consequent expressional suppressions of iNOS and COX-2.
Related JoVE Video
Ginsenoside Rc modulates Akt/FoxO1 pathways and suppresses oxidative stress.
Arch. Pharm. Res.
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
Ginsenoside Rc (Rc), a protopanaxadiol type ginsenoside, is the active component mainly responsible for the therapeutic and pharmacologic properties of ginseng, which are derived from its suppression of superoxide-induced free radicals. Forkhead box O (FoxO1) regulates various genes involved in cellular metabolism related to cell death and response to oxidative stress, and Rc is known to prevent FoxO1 phosphorylation by activation of PI3K/Akt and subsequent inhibition of AMP-activated protein kinase (AMPK) in cells exposed to tert-butylhydroperoxide (t-BHP). In the current study, we attempted the mechanism of increased catalase expression by Rc through inhibition of FoxO1 activation resulting from t-BHP-induced production of reactive species (RS). We found that overexpression of catalase induced by Rc resulted in suppression of RS production in kidney human embryo kidney 293T cells (HEK293T) cells, and that oxidative stress induced activation of PI3K/Akt and inhibition of the AMPK pathway and FoxO1 phosphorylation, leading to down-regulation of catalase, a FoxO1-targeting gene. In addition, treatment of HEK293T cells with Rc resulted in cAMP-response element-binding protein (CREB)-binding protein (CBP) regulated FoxO1 acetylation. Our results suggest that Rc modulates FoxO1 phosphorylation through activation of PI3K/Akt and inhibition of AMPK and FoxO1 acetylation through interaction with CBP and SIRT1, and that this leads to upregulation of catalase under conditions of oxidative stress.
Related JoVE Video
Related JoVE Video
Molecular targeted therapy for hepatocellular carcinoma: current and future.
World J. Gastroenterol.
PUBLISHED: 04-02-2013
Show Abstract
Hide Abstract
Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide. The majority of HCC cases occur in patients with chronic liver disease. Despite regular surveillance to detect small HCC in these patients, HCC is often diagnosed at an advanced stage. Because HCC is highly resistant to conventional systemic therapies, the prognosis for advanced HCC patients remains poor. The introduction of sorafenib as the standard systemic therapy has unveiled a new direction for future research regarding HCC treatment. However, given the limited efficacy of the drug, a need exists to look beyond sorafenib. Many molecular targeted agents that inhibit different pathways involved in hepatocarcinogenesis are under various phases of clinical development, and novel targets are being assessed in HCC. This review aims to summarize the efforts to target molecular components of the signaling pathways that are responsible for the development and progression of HCC and to discuss perspectives on the future direction of research.
Related JoVE Video
Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation.
Int. J. Oncol.
PUBLISHED: 04-01-2013
Show Abstract
Hide Abstract
Cancer upregulated gene (CUG) 2, as a novel oncogene, has been predominantly detected in various cancer tissues, such as ovary, liver, lung and colon. We recently showed that CUG2 elevates STAT1 activity, leading to resistance to infection by oncolytic vesicular stomatitis virus. To investigate a possible role for CUG2-induced activation of STAT1 in oncogenesis, we first established a colon cancer cell line stably expressing CUG2 (Colon26L5-CUG2). Colon26L5-CUG2 exhibited higher levels not only in phosphorylation of STAT1, but also phosphorylation of Jak1/Tyk2 compared to that of the control (Colon26L5-Vec) cell line. Inhibition of Akt or ERK activity reduced phosphorylation of STAT1 in Colon26L5-CUG2 cells whereas inhibition of p38 MAPK did not significantly decrease levels of STAT1 phosphorylation, indicating that cell proliferation signals may be involved in CUG2-mediated activation of STAT1. Suppression of STAT1 expression diminished cell migration and wound healing compared to the control cells. In addition, since CUG2 expression conferred resistance to DNA damage caused by doxorubicin treatment, we investigated whether STAT1 is involved in resistance to doxorubicin-induced cell death. We found that STAT1 was not activated in Colon26L5-Vec cells while phosphorylated STAT1 was maintained in Colon26L5-CUG2 cells during doxorubicin treatment. Furthermore, suppression of STAT1 expression sensitized Colon26L5-CUG2 cells to doxorubicin-induced apoptosis whereas the control cells exhibited resistance to doxorubicin. Taken together, our results suggest that CUG2 enhances metastasis and drug resistance through STAT1 activation, which eventually contributes to tumor progression.
Related JoVE Video
Caffeic acid regulates LPS-induced NF-?B activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells.
Arch. Pharm. Res.
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
The redox sensitive, proinflammatory nuclear transcription factor NF-?B plays a key role in inflammation. In a redox state disrupted by oxidative stress, pro-inflammatory genes are upregulated by the activation of NF-?B via diverse kinases. Thus, the search and characterization of new substances that modulate NF-?B are topics of considerable research interest. Caffeic acid is a component of garlic, some fruits, and coffee, and is widely used as a phenolic agent in beverages. In the present study, caffeic acid was examined with respect to the modulation of inflammatory NF-?B activation via the redox-related c-Src/ERK and NIK/IKK pathways via the reduction of oxidative stress. YPEN-1 cells (an endothelial cell line) were used to explore the molecular mechanism underlying the anti-inflammatory effect of caffeic acid by examining its modulation of NF-?B signaling pathway by LPS. Our results show that LPS-induced oxidative stress-related NF-?B activation upregulated pro-inflammatory COX-2, NF-?B targeting gene which were all inhibited effectively by caffeic acid. Our study shows that caffeic acid inhibits the activation of NF-?B via the c-Src/ERK and NIK/IKK signal transduction pathways. Our results indicate that antioxidative effect of caffeic acid and its restoration of redox balance are responsible for its anti-inflammatory action. Thus, the study provides new information regarding the anti-inflammatory properties of caffeic acid and the roles in the regulation of LPS-induced oxidative stress induces alterations in signal transduction pathways.
Related JoVE Video
Anti-melanogenic effect of (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione, a novel tyrosinase inhibitor.
Arch. Pharm. Res.
PUBLISHED: 03-24-2013
Show Abstract
Hide Abstract
We synthesized (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498) as a potential tyrosinase inhibitor. MHY498 potently inhibited mushroom tyrosinase activity (mean IC50 = 3.55 ?M) in a dose-dependent manner. MHY498 was more potent than the well-known tyrosinase inhibitor, kojic acid (mean IC50 = 22.79 ?M). When tested in B16F10 melanoma cells treated with ?-melanocyte stimulating hormone (?-MSH), MHY498 inhibited murine tyrosinase activity and decreased melanin production without inducing cytotoxicity. Docking models showed that the binding affinity of MHY498 to tyrosinase was higher than that of kojic acid, and docking simulation results indicated that the tyrosinase binding moieties of MHY498 and kojic acid were similar. Western blotting showed that tyrosinase inhibition by MHY498 partly resulted from the expressional modulations of tyrosinase and its transcription factor, microphthalmia-associated transcription factor, via the cAMP-PKA-CREB pathway. These findings suggest that MHY498 could be useful as an antimelanogenic agent for the prevention and treatment of diseases associated with skin pigmentation.
Related JoVE Video
Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
Biochim. Biophys. Acta
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Multidrug resistance is a major problem in the treatment of breast cancer, and a number of studies have attempted to find an efficient strategy with which to overcome it. In this study, we investigate the synergistic anticancer effects of resveratrol (RSV) and doxorubicin (Dox) against human breast cancer cell lines.
Related JoVE Video
Amnestic multiple cognitive domains impairment and periventricular white matter hyperintensities are independently predictive factors progression to dementia in mild cognitive impairment.
Int J Geriatr Psychiatry
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to determine whether clinical subtypes of MCI and severity of white matter hyperintensities (WMH) were associated with progression of MCI to dementia.
Related JoVE Video
The inhibitory effect of a synthetic compound, (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione (MHY498), on nitric oxide-induced melanogenesis.
Bioorg. Med. Chem. Lett.
PUBLISHED: 03-09-2013
Show Abstract
Hide Abstract
Nitric oxide (NO) and the NO/PKG signaling pathway play crucial roles in ultraviolet (UV)-induced melanogenesis, which is known to be related to the induction of tyrosinase. In an attempt to find a novel anti-melanogenic agent, we synthesized (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498). The purpose of this study was to investigate the effect of MHY498 on NO levels and on the NO-mediated signaling pathway using an in vitro model of melanogenesis. MHY498 inhibited 200 ?M sodium nitroprusside (SNP, a NO donor)-induced NO generation, dose-dependently and suppressed tyrosinase activity and melanin synthesis induced by SNP in B16F10 melanoma cells. To investigate the effect of MHY498 on NO-mediated signaling pathway, guanosine cyclic 3,5-monophosphate (cGMP) activities were measured using a cGMP EIA Kit and western blotting was performed to determine the effects of MHY498 on the gene expressions of tyrosinase and microphthalmia-associated transcription factor (MITF). The increased activity of cGMP by SNP was reduced dose-dependently by pretreatment with MHY498. Furthermore, MHY498 suppressed the expressions of tyrosinase and MITF stimulated by SNP. This study shows that enhancement of tyrosinase gene expression via the cGMP pathway is a probable primary mechanism of NO-induced melanogenesis and that the NO-mediated signaling pathway with the expression of MITF enhances melanogenesis. In addition, MHY498 was found to scavenge NO and to suppress the activity of the NO-mediated signaling pathway, and thus, to subsequently down-regulate tyrosinase expression and melanogenesis. This study suggests that MHY498 is a promising anti-melanogenic agent that targets the NO-induced cGMP signaling pathway.
Related JoVE Video
Characterization of a small molecule inhibitor of melanogenesis that inhibits tyrosinase activity and scavenges nitric oxide (NO).
Biochim. Biophys. Acta
PUBLISHED: 03-09-2013
Show Abstract
Hide Abstract
Excessive melanin production and accumulation are characteristics of a large number of skin diseases, including melasma, and post-inflammatory hyperpigmentation. During our on-going search for new agents with an inhibitory effect on tyrosinase, we synthesized a new type of tyrosinase inhibitor, 4-(thiazolidin-2-yl)benzene-1,2-diol (MHY-794), which directly inhibits mushroom tyrosinase.
Related JoVE Video
Effect of Dorzolamide/Timolol or Brinzolamide/Timolol prophylaxis on intravitreal anti-VEGF injection-induced intraocular hypertension.
Semin Ophthalmol
PUBLISHED: 03-02-2013
Show Abstract
Hide Abstract
To evaluate prospectively whether anti-glaucomatic drugs administered prior to intravitreal anti-vascular endothelial growth factor (VEGF) injection bevacizumab (Avastin,® Roche) or ranibizumab (Lucentis,® Novartis) prevents intraocular hypertension after the injection.
Related JoVE Video
Safety and efficacy of adjuvant pegylated interferon therapy for metastatic tumor antigen 1-positive hepatocellular carcinoma.
Cancer
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
Metastatic tumor antigen 1 (MTA1) overexpression is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). It has been suggested that pegylated interferon (Peg-IFN) can prevent the occurrence of HCC in patients who have chronic viral hepatitis. In this study, the authors examined whether postoperative adjuvant Peg-IFN therapy can reduce the recurrence of MTA1-positive HCC after curative surgical resection.
Related JoVE Video
De novo tyrosinase inhibitor: 4-(6,7-dihydro-5H-indeno[5,6-d]thiazol-2-yl)benzene-1,3-diol (MHY1556).
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-12-2013
Show Abstract
Hide Abstract
In this study, we have synthesized and studied de novo tyrosinase inhibitor, MHY1556, which showed significantly better efficacy than other pre-existing tyrosinase inhibitors in vitro experiments. The IC50 value of MHY1556 was 0.50?M which was significantly lower than that of kojic acid (IC50=53.95?M), which is a well-known tyrosinase inhibitor and was used as a positive control in this study. We predicted the tertiary structure of tyrosinase, simulated the docking with compound MHY1556 and confirmed that the compound strongly interacts with mushroom tyrosinase residues. Substitutions with a hydroxy group at both R1 and R3 of the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase, especially through the hydrogen bonding interaction of the hydroxyl group at R1 with GLY281. In addition, MHY1556 showed concentration-dependent inhibitory effects in melanin content assay where B16F10 melanoma cells were treated with ?-melanocyte stimulating hormone (?-MSH), and also there is no significant cytotoxicity of this compound in cell viability assay conducted in B16F10 melanoma cells. The tyrosinase activity assay results with MHY1556 also support its potent inhibitory effects. Therefore, our data strongly suggest MHY1556 suppresses the melanogenesis via a tyrosinase inhibitory effect.
Related JoVE Video
Clinical usefulness of endoscopic palliation in patients with biliary obstruction caused by hepatocellular carcinoma.
Digestion
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
To evaluate the clinical usefulness of endoscopic biliary drainage (EBD) in patients with hepatocellular carcinoma (HCC).
Related JoVE Video
Recurrences of hepatocellular carcinoma following complete remission by transarterial chemoembolization or radiofrequency therapy: Focused on the recurrence patterns.
Hepatol. Res.
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
In this study, we analyzed the rates and patterns of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA), and also examined the differences of recurrence patterns between TACE-treated and RFA-treated groups.
Related JoVE Video
Predisposing factors of hepatocellular carcinoma recurrence following complete remission in response to transarterial chemoembolization.
Dig. Dis. Sci.
PUBLISHED: 01-02-2013
Show Abstract
Hide Abstract
The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE).
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.