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Find video protocols related to scientific articles indexed in Pubmed.
H19 long noncoding RNA controls the mRNA decay promoting function of KSRP.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-12-2014
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Long noncoding RNAs (lncRNAs) interact with protein factors to regulate different layers of gene expression transcriptionally or posttranscriptionally. Here we report on the functional consequences of the unanticipated interaction of the RNA binding protein K homology-type splicing regulatory protein (KSRP) with the H19 lncRNA (H19). KSRP directly binds to H19 in the cytoplasm of undifferentiated multipotent mesenchymal C2C12 cells, and this interaction favors KSRP-mediated destabilization of labile transcripts such as myogenin. AKT activation induces KSRP dismissal from H19 and, as a consequence, myogenin mRNA is stabilized while KSRP is repurposed to promote maturation of myogenic microRNAs, thus favoring myogenic differentiation. Our data indicate that H19 operates as a molecular scaffold that facilitates effective association of KSRP with myogenin and other labile transcripts, and we propose that H19 works with KSRP to optimize an AKT-regulated posttranscriptional switch that controls myogenic differentiation.
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Clinical significance of pathological complete response in patients with metastatic gastrointestinal stromal tumors after imatinib mesylate treatment - lessons learned.
Anticancer Res.
PUBLISHED: 11-05-2014
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Imatinib mesylate (IM) has substantial efficacy in patients with metastatic gastrointestinal stromal tumors (GISTs), and pathological complete response (pCR) following IM treatment has been sporadically reported; however, its clinical significance for GIST needs to be clarified.
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Life history strategy and young adult substance use.
Evol Psychol
PUBLISHED: 11-04-2014
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This study tested whether life history strategy (LHS) and its intergenerational transmission could explain young adult use of common psychoactive substances. We tested a sequential structural equation model using data from the National Longitudinal Survey of Youth. During young adulthood, fast LHS explained 61% of the variance in overall liability for substance use. Faster parent LHS predicted poorer health and lesser alcohol use, greater neuroticism and cigarette smoking, but did not predict fast LHS or overall liability for substance use among young adults. Young adult neuroticism was independent of substance use controlling for fast LHS. The surprising finding of independence between parent and child LHS casts some uncertainty upon the identity of the parent and child LHS variables. Fast LHS may be the primary driver of young adult use of common psychoactive substances. However, it is possible that the young adult fast LHS variable is better defined as young adult mating competition. We discuss our findings in depth, chart out some intriguing new directions for life history research that may clarify the dimensionality of LHS and its mediation of the intergenerational transmission of substance use, and discuss implications for substance abuse prevention and treatment.
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Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity.
Nucleic Acids Res.
PUBLISHED: 10-28-2014
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Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-? by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-? mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
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Plasma chromogranin A levels predict survival and tumor response in patients with advanced gastroenteropancreatic neuroendocrine tumors.
Anticancer Res.
PUBLISHED: 10-03-2014
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To correlate the baseline and change of chromogranin A (CgA) levels with patient survival and tumor response in Asian patients with advanced gastro-enteropancreatic neuroendocrine tumors (GEP-NETs).
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The impacts of migraine and anxiety disorders on painful physical symptoms among patients with major depressive disorder.
J Headache Pain
PUBLISHED: 09-23-2014
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No study has simultaneously investigated the impacts of migraine and anxiety disorders on painful physical symptoms (PPS) among patients with major depressive disorder (MDD). The study aimed to investigate this issue.
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CD97 inhibits cell migration in human fibrosarcoma cells by modulating TIMP-2/MT1- MMP/MMP-2 activity - role of GPS autoproteolysis and functional cooperation between the N- and C-terminal fragments.
FEBS J.
PUBLISHED: 09-22-2014
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CD97 is a tumor-associated adhesion-class G-protein-coupled receptor involved in modulating cell migration. Adhesion-class G-protein-coupled receptors are characterized by proteolytic cleavage at a G-protein-coupled receptor proteolysis site (GPS) into an N-terminal fragment (NTF) and a C-terminal fragment (CTF), which remain associated noncovalently. The molecular mechanism and the role of GPS proteolysis in CD97-modulated cell migration are not completely understood. We report here that CD97 expression in HT1080 fibrosarcoma cells enhanced tissue inhibitor of metalloproteinase-2 secretion, leading to reduced membrane type 1 matrix metalloproteinase and matrix metalloproteinase 2 activities. This, in turn, impaired cell migration and invasion in vitro and lung macrometastasis in vivo. CD97 expression also upregulated the expression of integrins, promoting cell adhesion. Importantly, these cellular functions absolutely required the presence of both the NTF and the CTF of CD97, confirming functional cooperation between the two receptor subunits. CD97 gene knockdown reversed these phenotypic changes. We conclude that GPS proteolysis and the functional interplay between the NTF and the CTF are indispensible for CD97 to inhibit HT1080 cell migration by suppressing matrix metalloproteinase activity.
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Alterations of the mTOR Pathway in Hepatic Angiomyolipoma with Emphasis on the Epithelioid Variant and Loss of Heterogeneity of the TSC1/TSC2 Genes.
Histopathology
PUBLISHED: 09-20-2014
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The significance of the epithelioid type and the corresponding molecular alterations in hepatic angiomyolipoma (AML) have not been elucidated.
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The novel Aryl hydrocarbon receptor inhibitor biseugenol inhibits gastric tumor growth and peritoneal dissemination.
Oncotarget
PUBLISHED: 09-17-2014
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Biseugenol (Eug) is known to antiproliferative of cancer cells; however, to date, the antiperitoneal dissemination effects have not been studied in any mouse cancer model. In this study, Aryl hydrocarbon receptor (AhR) expression was associated with lymph node and distant metastasis in patients with gastric cancer and was correlated with clinicolpathological pattern. We evaluated the antiperitoneal dissemination potential of knockdown AhR and Biseugenol in cancer mouse model and assessed mesenchymal characteristics. Our results demonstrate that tumor growth, peritoneal dissemination and peritoneum or organ metastasis implanted MKN45 cells were significantly decreased in shAhR and Biseugenol-treated mice and that endoplasmic reticulum (ER) stress was caused. Biseugenol-exposure tumors showed acquired epithelial features such as phosphorylation of E-cadherin, cytokeratin-18 and loss mesenchymal signature Snail, but not vimentin regulation. Snail expression, through AhR activation, is an epithelial-to-mesenchymal transition (EMT) determinant. Moreover, Biseugenol enhanced Calpain-10 (Calp-10) and AhR interaction results in Snail downregulation. The effect of shCalpain-10 in cancer cells was associated with inactivation of AhR/Snail promoter binding activity. Inhibition of Calpain-10 in gastric cancer cells by short hairpin RNA or pharmacological inhibitor was found to effectively reduced growth ability and vessel density in vivo. Importantly, knockdown of AhR completed abrogated peritoneal dissemination. Herein, Biseugenol targeting ER stress provokes Calpain-10 activity, sequentially induces reversal of EMT and apoptosis via AhR may involve the paralleling processes. Taken together, these data suggest that Calpain-10 activation and AhR inhibition by Biseugenol impedes both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT.
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Interval and Continuous Exercise Regimens Suppress Neutrophil-derived Microparticle Formation and Neutrophil-promoted Thrombin Generation under Hypoxic Stress.
Clin. Sci.
PUBLISHED: 08-18-2014
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Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. This study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training (AIT; 3-minute intervals at 40% and 80%VO2max) or moderate continuous training (MCT; sustained 60%VO2max) for 30 min/day, 5 days/week for 5 weeks, or to a control group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100W under 12%O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography, respectively. Before the intervention, HE 1) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), 2) increased total and tissue factor-rich/phosphatidylserine-exposed NDMP counts, and 3) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of VO2max than MCT did. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased tissue factor-rich/phosphatidylserine-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expressions of procoagulant factors during HE,which may reduce thrombotic risk evoked by hypoxia.
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Macular retinal detachment associated with intrachoroidal cavitation in myopic patients.
Graefes Arch. Clin. Exp. Ophthalmol.
PUBLISHED: 08-13-2014
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To investigate the clinical characteristics and treatment outcomes of macular retinal detachment (MRD) associated with intrachoroidal cavitation (ICC) in myopic patients.
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N-3 polyunsaturated fatty acids decrease levels of doxorubicin-induced reactive oxygen species in cardiomyocytes -- involvement of uncoupling protein UCP2.
J. Biomed. Sci.
PUBLISHED: 07-22-2014
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BackgroundUse of the chemotherapeutic drug doxorubicin (DOX) is associated with serious cardiotoxicity, as it increases levels of reactive oxygen species (ROS). N-3 polyunsaturated fatty acid dietary supplements can be of benefit to patients undergoing cancer therapy. The aims of this study were to determine whether DOX-induced cardiotoxicity is related to mitochondrial uncoupling proteins and whether eicosapentaenoic acid (EPA, C20:5 n-3) or docosahexaenoic acid (DHA, C22:6 n-3) affects DOX-induced cardiomyocyte toxicity.ResultsTreatment of H9C2 cells with DOX resulted in decreased cell viability and UCP2 expression. Treatment with 100 ¿M EPA or 50 ¿M DHA for 24 h resulted in a maximal mitochondria concentration of these fatty acids and increased UCP2 expression. Pretreatment with 100 ¿M EPA or 50 ¿M DHA prevented the DOX-induced decrease in UCP2 mRNA and protein levels, but these effects were not seen with EPA or DHA and DOX cotreatment. In addition, the DOX-induced increase in ROS production and subsequent mitochondrial membrane potential change (¿¿) were significantly attenuated by pretreatment with EPA or DHA.ConclusionEPA or DHA pre-treatment inhibits the DOX-induced decrease in UCP2 expression, increase in ROS production, and subsequent mitochondrial membrane potential change that contribute to the cardiotoxicity of DOX.
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The reduced autophagic response by oxidative stress in angiotensin II-induced hypertrophic H9C2 cells causes more apoptotic cell death.
Exp. Biol. Med. (Maywood)
PUBLISHED: 07-10-2014
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Autophagy is an important process in the pathogenesis of cardiovascular diseases, and angiotensin II (Ang II) plays a causative role in the induction of cardiomyocyte autophagy. The purpose of this study was to explore whether, under conditions of oxidative stress, levels and types of cell death were different in untreated and Ang II-treated cardiomyocytes (H9C2 cells). Treatment with 20?µM Ang II induced cardiac hypertrophy in H9C2 cells, with increased expression of the hypertrophic markers c-Fos, ß-myosin heavy chain, atrial natriuretic factor (ANF), and brain natriuretic factor (BNF). Under normal conditions, there was no difference in the levels of autophagic vacuoles and apoptotic bodies in untreated and Ang II-treated H9C2 cells. However, oxidative stress generated by 100?µM H2O2 triggered autophagy in untreated control cells, but had a reduced effect in Ang II-induced hypertrophic cells, resulting in more cell death, and this was associated with a decrease in connexin 43 expression. Blocking this autophagic response with 3-methyladenine resulted in a significant increase in cell death and apoptosis of H9C2 cells but did not significantly affect the response of Ang II-treated cells. The autophagic response to 100?µM H2O2 provides a survival advantage for cells and this is reduced by Ang II treatment.
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The subfamily-specific assembly of Eag and Erg K+ channels is determined by both the amino and the carboxyl recognition domains.
J. Biol. Chem.
PUBLISHED: 07-09-2014
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A functional voltage-gated K(+) (Kv) channel comprises four pore-forming ?-subunits, and only members of the same Kv channel subfamily may co-assemble to form heterotetramers. The ether-à-go-go family of Kv channels (KCNH) encompasses three distinct subfamilies: Eag (Kv10), Erg (Kv11), and Elk (Kv12). Members of different ether-à-go-go subfamilies, such as Eag and Erg, fail to form heterotetramers. Although a short stretch of amino acid sequences in the distal C-terminal section has been implicated in subfamily-specific subunit assembly, it remains unclear whether this region serves as the sole and/or principal subfamily recognition domain for Eag and Erg. Here we aim to ascertain the structural basis underlying the subfamily specificity of ether-à-go-go channels by generating various chimeric constructs between rat Eag1 and human Erg subunits. Biochemical and electrophysiological characterizations of the subunit interaction properties of a series of different chimeric and truncation constructs over the C terminus suggested that the putative C-terminal recognition domain is dispensable for subfamily-specific assembly. Further chimeric analyses over the N terminus revealed that the N-terminal region may also harbor a subfamily recognition domain. Importantly, exchanging either the N-terminal or the C-terminal domain alone led to a virtual loss of the intersubfamily assembly boundary. By contrast, simultaneously swapping both recognition domains resulted in a reversal of subfamily specificity. Our observations are consistent with the notion that both the N-terminal and the C-terminal recognition domains are required to sustain the subfamily-specific assembly of rat Eag1 and human Erg.
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Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/?-catenin pathway.
Oncotarget
PUBLISHED: 06-17-2014
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Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active ?-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and ?-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
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Triggers of suicide ideation and protective factors of actually executing suicide among first onset cases in older psychiatric outpatients: a qualitative study.
BMC Psychiatry
PUBLISHED: 05-21-2014
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BackgroundSuicide is a global issue among the elderly, but few studies have explored the experiences of suicide ideation in older Asian psychiatric outpatients.MethodOlder psychiatric outpatients (N¿=¿24) were recruited by convenience from one medical centre and one regional hospital in northern Taiwan. Participants were recruited if they met these inclusion criteria: 1) ¿65 years old, 2) without severe cognitive deficit, 3) outpatients in the psychiatric clinics at the selected hospitals, and 4) self-reported first episode of suicidal ideation within the previous year. Data were collected in individual interviews using a semi-structured guide and analysed by content analysis.ResultsSuicide ideation was triggered by illness and physical discomfort, conflicts with family members/friends, illness of family members, death of family members/friends, and loneliness. Participants¿ reasons for not executing suicide were family members¿ and friends¿ support, receiving treatment, finding a way to shift their attention, fear of increasing pressure on one¿s children, religious beliefs, and not knowing how to execute suicide.ConclusionUnderstanding these identified triggers of suicide ideation may help psychiatrists open a channel for conversation with their elderly clients and more readily make their diagnosis. Understanding these identified protective factors against executing suicide can help psychiatrists not only treat depression, but also enhance protective factors for their clients.
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Long-term outcome of foveolar internal limiting membrane nonpeeling for myopic traction maculopathy.
Retina (Philadelphia, Pa.)
PUBLISHED: 05-03-2014
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To investigate the long-term results of a novel technique to preserve the foveolar cone without peeling off the foveolar internal limiting membrane (ILM) during myopic traction maculopathy surgery.
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KSRP and MicroRNA 145 are negative regulators of lipolysis in white adipose tissue.
Mol. Cell. Biol.
PUBLISHED: 04-14-2014
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White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp(-/-) eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through posttranscriptional regulation of miR-145 expression.
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KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression.
Diabetes
PUBLISHED: 04-10-2014
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Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is a promising strategy for combating obesity. Here, we find that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, causes a reduction in body adiposity. The expression of brown fat-selective genes is increased in subcutaneous/inguinal WAT (iWAT) of Ksrp(-/-) mice because of the elevated expression of PR domain containing 16 and peroxisome proliferator-activated receptor gamma coactivator 1?, which are key regulators promoting the brown fat gene program. The expression of microRNA (miR)-150 in iWAT is decreased due to impaired primary miR-150 processing in the absence of KSRP. We show that miR-150 directly targets and represses Prdm16 and Ppargc1a, and that forced expression of miR-150 attenuates the elevated expression of brown fat genes caused by KSRP deletion. This study reveals the in vivo function of KSRP in controlling brown-like transformation of iWAT through post-transcriptional regulation of miR-150 expression.
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Development of a dietary induced metabolic syndrome model using miniature pigs-invovlement of ampk and sirt1.
Eur. J. Clin. Invest.
PUBLISHED: 04-09-2014
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During the progression of the metabolic syndrome (MetS), cardiovascular diseases (CVD) appear clinically in many individuals and cause death. As a result, it is essential to set-up an optimal animal model to study the mechanism of MetS leading to CVD. SIRT1 and AMPK are the master regulators of lipid and carbohydrate metabolism. The objective of this study was to establish a miniature pig model of Western diet-induced MetS and investigate the role of SIRT1/AMPK during MetS development.
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Malignant transformation in 5071 southern Taiwanese patients with potentially malignant oral mucosal disorders.
BMC Oral Health
PUBLISHED: 04-08-2014
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Oral cancers can be preceded by clinically evident oral potentially malignant disorders (OPMDs). The current study evaluated the rate and the time of malignant transformation in the various OPMDs in a cohort of patients from southern Taiwan. Parameters possibly indicative for malignant transformation of OPMDs, such as epidemiological and etiological factors, and clinical and histopathological features were also described.
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Role of KSRP in control of type I interferon and cytokine expression.
J. Interferon Cytokine Res.
PUBLISHED: 04-05-2014
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Cytokines and chemokines are key participants in pathways that drive inflammatory, immune, and other cellular responses to exogenous insults such as infection, trauma, and physiological stress. Persistent and aberrant expression of these factors has been linked to autoimmune, degenerative, and neoplastic diseases. Consequently, cytokine and chemokine expression is tightly governed at each level of gene regulation. Recent studies have demonstrated a role for KH-type splicing regulatory protein (KSRP) in curtailing cytokine and chemokine expression through transcriptional and post-transcriptional mechanisms, including promotion of microRNA maturation. Understanding the role of KSRP in cytokine mRNA metabolism should identify promising targets for the modulation of immune and inflammatory responses.
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Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy.
J Transl Med
PUBLISHED: 03-31-2014
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We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA).
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Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccharide-stimulated RAW264.7 cells.
Mol Med Rep
PUBLISHED: 03-28-2014
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Perilla leaves are widely used in Chinese herbal medicine and in Japanese herbal agents used to treat respiratory diseases. This study aimed to investigate the anti?inflammatory effects and the underlying mechanisms of Perilla frutescens leaf extract (PLE). Murine macrophage RAW264.7 cells were used as a model. Cell viability and morphological changes were studied by the MTT assay and microscopy. mRNA expression of pro?inflammatory mediators was assessed by both semi?quantitative reverse transcription?polymerase chain reaction (RT?PCR) and quantitative (q) RT?PCR. Nitric oxide (NO) and prostaglandin E2 (PGE2) production were analyzed by the Griess test and sandwich enzyme?linked immunosorbent assay (ELISA), respectively. The activation of kinase cascades was studied by immunoblotting. Our findings showed that PLE slightly affects cell viability, but alleviates LPS?induced activation of RAW264.7 cells. Furthermore, PLE significantly reduced the LPS?induced mRNA expression of the interleukin (IL)?6, IL?8, tumor necrosis factor?? (TNF??), cyclooxygenase?2 (COX?2) and inducible nitric oxide synthase (iNOS), genes in a dose?dependent manner. In addition, PLE reduced NO production and PGE2 secretion induced by LPS. PLE also inhibited activation of mitogen?activated protein kinases (MAPKs), increased the cytosolic I?B? level, and reduced the level of nuclear factor (NF)??B. Taken together, these findings indicate that PLE significantly decreases the mRNA expression and protein production of pro?inflammatory mediators, via the inhibition of extracellular?signal?regulated kinase (ERK)1/2, c?Jun N?terminal kinase (JNK), p38, as well as NF??B signaling in RAW264.7 cells stimulated with LPS.
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Adiponectin receptor 1 overexpression reduces lipid accumulation and hypertrophy in the heart of diet-induced obese mice - possible involvement of oxidative stress and autophagy.
Endocr. Res.
PUBLISHED: 03-28-2014
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Abstract Background: Studies show that adiponectin and its receptors (AdipoR1 and 2) play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with downregulated adiponectin signaling; however, research has not clarified the functions of AdipoR1 in vivo.
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KSRP controls pleiotropic cellular functions.
Semin. Cell Dev. Biol.
PUBLISHED: 03-17-2014
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The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional mechanisms: (i) by promoting decay of unstable mRNAs and (ii) by favoring maturation from precursors of select microRNAs (miRNAs) including the prototypical tumor suppressor let-7. Studies performed in primary and cultured cells as well as in mice proved that the ability of KSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response.
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Dual thermo- and pH-responsive zwitterionic sulfobataine copolymers for oral delivery system.
Macromol Rapid Commun
PUBLISHED: 03-15-2014
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A novel oral delivery system consisting of thermoresponsive zwitterionic poly(sulfobetaine methacrylate) (PSBMA) and pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) is synthesized via free radical polymerization. This copolymer can self-aggregate into nanoparticles via electrostatic attraction between ammonium cation and sulfo-anion of PSBMA and successfully encapsulate anticancer drug, curcumin (CUR), with highest loading content of 2.6% in the P(SBMA-co-DPA) nanoparticles. The stimuli-responsive phase transition behaviors of P(SBMA-co-DPA) copolymers at different pH buffer solution show pH-dependent upper critical solution temperature (UCST) attributed to the influence of protonation/deprotonation of the pH-responsive DPA segments. Through the delicate adjustment of the PSBMA/PDPA molar ratios, the stimuli-responsive phase transition could be suitable for physiological environment. The kinetic drug release profiles demonstrate that P(SBMA-co-DPA) nanoparticles have the potential as oral delivery carriers due to their effective release of entrapped drugs in the stimulated intestinal fluid and preventing the deterioration of drug in stimulated gastric fluid.
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High-purity separation of cancer cells by optically induced dielectrophoresis.
J Biomed Opt
PUBLISHED: 03-14-2014
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Detecting and concentrating cancer cells in peripheral blood is of great importance for cancer diagnosis and prognosis. Optically induced dielectrophoresis (ODEP) can achieve high resolution and low optical intensities, and the electrode pattern can be dynamically changed by varied light patterns. By changing the projected light pattern, it is demonstrated to separate high-purity gastric cancer cell lines. Traditionally, the purity of cancer cell isolation by negative selection is 0.9% to 10%; by positive selection it is 50% to 62%. An ODEP technology is proposed to enhance the purity of cancer cell isolation to about 77%.
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Utility of fluorescence in situ hybridization for ploidy and p57 immunostaining in discriminating hydatidiform moles.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-25-2014
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Discrimination between complete moles (CMs), partial moles (PMs), and hydropic abortions (HAs) is important as the risk of persistent gestational trophoblastic disease (GTD) differs for each condition. We evaluated whether ancillary fluorescence in situ hybridization (FISH) with a set of chromosome enumeration probes (CEP) for chromosomes X, Y, and 17 and p57 immunostaining could improve the clinical diagnosis. Forty-one products of conception (POC) were reclassified according to clinical performance, morphology, p57 immunostaining results, and FISH results. The accuracy of histological examination alone was 85% for the original diagnosis. FISH analysis showed diploidy in 19 of 20 CMs and triploidy in 4 of 6 PMs. The concordance rate was 92.5% on using the CEP probes. p57 Staining was negative in all CMs and positive in all PMs and HAs. Chromosomal abnormality was detected in 3 cases of HA by using FISH. In conclusion, combined p57 immunostaining and FISH with a set of 3 CEP probes for chromosomes X, Y, and 17 could be useful in the classification of hydatidiform moles.
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Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury.
J. Pineal Res.
PUBLISHED: 02-23-2014
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This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-? level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper-, cytoxic-, and regulatory-T cells at post-CLP 72 hr exhibited the same pattern as that of circulating TNF-? among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, and higher in CLP-A-ADMSC than in CLP-melatonin-A-ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF-1?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin- than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.
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Prognostic factors in Epstein-Barr virus-associated stage I-III gastric carcinoma: implications for a unique type of carcinogenesis.
Oncol. Rep.
PUBLISHED: 02-20-2014
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Epstein-Barr virus-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. However, the prognostic factors remain unclear, particularly in UICC/AJCC stage I-III cancer. We retrospectively enrolled 1,020 patients with stage I-III gastric cancer that received radical gastrectomy with lymphadenectomy. Formalin-fixed, paraffin?embedded surgical specimens were retrieved to construct tissue microarrays. EBV positivity was identified by in situ hybridization with EBV-encoded small RNA, and the histological classification was reviewed. Fifty-two cases of EBVaGC were identified, exhibiting a male predominance (p=0.003), a higher prevalence in stump cancer (p<0.001), and poorly differentiated carcinoma (p=0.010) compared with the controls. The survival analysis revealed no difference in survival between the EBVaGC cases and the EBV-negative cases (p=0.977). The multivariate analysis showed that EBVaGC cases with a tumor size >5 cm, non-lymphoepithelioma-like carcinoma (LELC), or a lymph node ratio >0.15 had a worse overall survival (hazard ratio 2.884, 12.178 and 19.352; p=0.027, 0.005 and <0.0001, respectively). The depth of tumor invasion and the number of lymph node metastases did not reach statistical significance (p=0.834 and 0.833, respectively). These prognostic factors, tumor size, LELC classification and lymph node ratio, may reflect a unique type of carcinogenesis of EBVaGC and may be considered when selecting high-risk patients for adjuvant treatment.
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Complex IV subunit 1 defect predicts postoperative survival in hepatocellular carcinoma.
Oncol Lett
PUBLISHED: 02-20-2014
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Mitochondrial oxidative phosphorylation (OXPHOS) is responsible for adenosine triphosphate synthesis and OXPHOS deficiency plays a significant role in tumorigenesis. The defects of mitochondrial-encoded OXPHOS subunits have been found in normal and cirrhotic liver, however their contributions in hepatocellular carcinoma (HCC) are not clear. The present study aimed to examine these defects in resected HCC tissues. In total, 102 human HCC tissues were collected from patients undergoing curative resection, and immunohistochemical staining was performed to assess tissue expression of complex I subunit 6, complex III subunit 3, complex IV subunit 1 (CIV-1) and complex V subunit 6. Cox proportional hazard model analysis was performed, including all clinicopathological factors, to postoperatively estimate the overall survival rate. The results showed that the majority of HCC tissues contained various degrees of expression defects for OXPHOS subunits. Among these, the major CIV-1 defect (expression defect area of >25% of the examined area) (P<0.001) and early distant metastasis (P<0.001) were independently associated with the overall survival rate. Kaplan-Meier analysis also demonstrated that the major CIV-1 defect was significantly associated with a poor overall survival rate (log-rank, P=0.002). The findings in the present study clearly indicate that the major CIV-1 expression defect may serve as an independent negative prognostic factor in HCC patients following curative resection.
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Prognostic factors in adult patients with solid cancers and bone marrow metastases.
Asian Pac. J. Cancer Prev.
PUBLISHED: 02-18-2014
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Solid cancers with bone marrow metastases are rare but lethal. This study aimed to identify clinical factors predictive of survival in adult patients with solid cancers and bone marrow metastases.
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How antepartum and postpartum acute urinary retention affects the function and structure of the rat bladder.
Int Urogynecol J
PUBLISHED: 02-11-2014
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To examine the effect of acute urinary retention (AUR) on the urodynamic function and molecular structure of rat bladders in pregnancy and after parturition.
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Comprehensive care improves physical recovery of hip-fractured elderly Taiwanese patients with poor nutritional status.
J Am Med Dir Assoc
PUBLISHED: 01-14-2014
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The effects of nutritional management among other intervention components have not been examined for hip-fractured elderly persons with poor nutritional status. Accordingly, this study explored the intervention effects of an in-home program using a comprehensive care model that included a nutrition-management component on recovery of hip-fractured older persons with poor nutritional status at hospital discharge.
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Unmet supportive care needs and characteristics of family caregivers of patients with oral cancer after surgery.
Psychooncology
PUBLISHED: 01-08-2014
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The aim of this study was to identify factors associated with unmet supportive care needs in family caregivers of patients with oral cancer after surgery.
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Defects in the Acquisition of Tumor-Killing Capability of CD8+ Cytotoxic T Cells in Streptozotocin-Induced Diabetic Mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNF? assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNF? determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts.
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Impulsivity links reward and threat sensitivities to substance use: a functional model.
Front Psychol
PUBLISHED: 01-01-2014
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This study used structural equations modeling and undergraduate student data to examine the effects of reward and threat sensitivities on substance use, along with the extent to which impulsivity explained these effects. Our results suggest that impulsivity may translate inversely related reward and threat sensitivities into substance use, completely mediate the effect between threat sensitivity and substance use, and partially mediate the effect between reward sensitivity and substance use. Our results also suggest that individuals with a combination of higher levels on both reward and threat sensitivities may be most impulsive and vulnerable to heightened substance use. We discuss implications for research at the interface of personality and substance use and also substance abuse prevention and treatment.
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Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury.
Am J Transl Res
PUBLISHED: 01-01-2014
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This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury.
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Validity and clinical utilization of the Chinese version of the Gotland Male Depression Scale at a men's health polyclinic.
Neuropsychiatr Dis Treat
PUBLISHED: 01-01-2014
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Symptoms of depression in males, such as aggression and irritability, are different from those in females. However, there are no adequate scales for detecting possible diagnoses in the Chinese population. The aim of this study was to assess whether the Chinese version of the Gotland Male Depression Scale (CV-GMDS) could identify male depression as effectively as the English version.
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The role of the mecA gene in oxacillin resistance in a pvl-positive:ST59 genetic background of a Staphylococcus aureus clinical strain.
Antimicrob. Agents Chemother.
PUBLISHED: 11-25-2013
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The most prevalent community-associated methicillin-resistant Staphylococcus aureus (C-MRSA) strains in Taiwan, ST59 clones, carry staphylococcal cassette chromosome mec (SCCmec) type V and, to a lesser extent, type IV. These strains show wide variation in sensitivity to oxacillin, but the reasons for this variation are unknown. Here we compared the sequence of the mecA gene from different SCCmec type clinical strains and found they contain different mecA promoter mutations. Analysis of mecA promoter activity by reporter-gene fusions showed that single base substitutions in the promoter have a strong influence on mecA transcription. The different mecA variants including promoter sequences were expressed in the methicillin-sensitive Staphylococcus aureus (MSSA) strain C195 (ST59 background). PBP2a production among the parental and promoter mutant mecA genes showed a close correlation with mecA transcription levels. Furthermore, the quantity of PBP2a also closely correlated with the level of oxacillin resistance in the C195 background. Our data suggest that mecA promoter mutations play an important role in determining the level of oxacillin resistance. The mecA promoter mutation G-25A (25 bases upstream of the mecA translation start site) was found to be associated with high oxacillin minimum inhibitory concentration (MIC) (256 ?g/ml), G-7T conferred a moderate oxacillin MIC (32-64 ?g/ml), C-33T showed a low oxacillin MIC (4-8 ?g/ml), and A-38G reversed the effect of the C-33T mutation, restoring the oxacillin resistance level in the double mutant A-38G/C-33T. These observations may explain why C-MRSA strains in Taiwan carrying SCCmec type IV or V have such enormous variation in oxacillin MIC.
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Change of glycaemic control and predictors in diabetes patients: longitudinal observational study during the one year after hospital discharge.
Int J Nurs Pract
PUBLISHED: 10-05-2013
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Glycated haemoglobin (HbA1c) might reflect glycaemic control in persons with diabetes. Study aims were to identify changes in glycated haemoglobin values and predictors (baseline coping behaviour, fasting plasma glucose, disease-related and demographic factors) in patients during 1 year after hospital discharge. A longitudinal prospective design with convenience sampling was used. Subjects were recruited from a community hospital in Taiwan. Measures included Jalowiec Coping Scale, fasting plasma glucose, HbA1c values, and demographics. Generalized estimating equation was used to determine factors of change in glycated haemoglobin. A total of 57 patients completed 1 year of follow-up. Half did not receive diabetes mellitus education and regular exercise. Patients glycated haemoglobin levels follow controls at 6 months after discharge. Patients with higher levels of blood glucose, less problem-focused coping and greater emotion-focused coping were associated with poor glycaemic control. Education programmes should involve individual-centred care and health behaviours for prevention of diabetes complications.
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Depression and predictors in Taiwanese survivors with oral cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-03-2013
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Depression is a comorbid disabling problem and potentially affects patient likelihood of survival. The aims of this study were to recognize the characteristics of depression and investigate associated predictor factors in patients with oral cancers.
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Segregation of signaling proteins as prognostic predictors for local recurrence and distant metastasis in hepatocellular carcinoma.
Int. J. Oncol.
PUBLISHED: 09-25-2013
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Postoperative recurrence of hepatocellular carcinoma (HCC) is presented as local recurrence (LR) or extrahepatic metastasis (EHM). Recent studies indicated that EHM requires additional cellular alterations. This study aimed to examine the clinical and molecular prognostic predictors of these two events. HCC patients (289) [training cohort (n=160) and verification cohort (n=129)] receiving surgical resection of hepatomas were included. The expression levels of six signaling molecules were quantitatively assessed for prognostic analysis. Clustering analysis revealed similar expression profiles between cancer (T) and non-cancer (N) liver tissues in the same individuals. Univariate analysis showed that phosphorylated mammalian target of rapamycin (mTOR)-T was associated with LR-free survival (P=0.002), whereas extracellular signal-related kinase (ERK2)-T (P=0.005), AKT-T (P=0.001) and glycogen synthase kinase (GSK)-T/N ratio (P=0.008) were associated with EHM-free survival. When clinical predictors were added for multivariate analysis, only prolonged prothrombin time (P=0.003) and tumor number (P=0.031) was independently associated with LR-free survival, whereas age (P=0.019), creatinine levels (P=0.001) and AKT-T (P=0.004) were associated with EHM-free survival. These factors were further examined in the verification cohort. In conclusion, postoperative LR and EHM in HCC were associated with separable sets of clinical and molecular predictors.
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Recurrence of corneal neovascularization associated with lipid deposition after subconjunctival injection of bevacizumab.
Cornea
PUBLISHED: 09-24-2013
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To report 7 cases of recurrent corneal neovascularization (NV) and lipid deposition after subconjunctival injection of bevacizumab for the treatment of corneal NV-induced lipid keratopathy.
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Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.
Curr. Med. Chem.
PUBLISHED: 09-06-2013
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Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic ?-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic ?-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed.
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An Internet-based health management platform may effectively reduce the risk factors of metabolic syndrome among career women.
Taiwan J Obstet Gynecol
PUBLISHED: 08-07-2013
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The purpose of this study is to target career women with metabolic syndrome (Mets) risk factors and investigate the effectiveness of using a health management platform (HMP) to improve health behavior and reduce Mets risk factors.
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The effectiveness of light/dark exposure to treat insomnia in female nurses undertaking shift work during the evening/night shift.
J Clin Sleep Med
PUBLISHED: 07-16-2013
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The present study investigated whether bright light exposure during the first half of the evening/night shift combined with light attenuation in the morning is effective in improving sleep problems in nurses undertaking rotating shift work who suffer from clinical insomnia.
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The "Aging Males Symptoms" (AMS) Scale assesses depression and anxiety.
Aging Male
PUBLISHED: 07-04-2013
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Emotional distress may be associated with severe aging symptoms. This study aimed to investigate aging symptoms in male psychiatric outpatients and their relationship with anxiety and depression.
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Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity.
J. Biomed. Sci.
PUBLISHED: 07-02-2013
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This study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals.
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Adiponectin receptor 1 enhances fatty acid metabolism and cell survival in palmitate-treated HepG2 cells through the PI3 K/AKT pathway.
Eur J Nutr
PUBLISHED: 06-20-2013
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Hepatic lipid overloading induces lipotoxicity which can cause hepatocyte damage, fibrosis, and eventually progress to cirrhosis, which is associated with nonalcoholic fatty liver disease. Adiponectin receptors play important roles in regulating lipid metabolism. In this study, we used a lentivirus system to overexpress the adiponectin receptor 1 (AdipoR1) in HepG2 cells to define the role of adiponectin and its receptor 1 in the development of fatty liver syndrome.
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Liver transplantation in patients with hepatitis B virus-related hepatocellular carcinoma: the influence of viral characteristics on clinical outcome.
Ann. Surg. Oncol.
PUBLISHED: 06-13-2013
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Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT.
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The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection.
World J Surg Oncol
PUBLISHED: 06-01-2013
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The expression of CK19 in primary hepatocellular carcinoma (HCC) is associated with a poor outcome. However, few studies have investigated the expression profile of CK19 in regional lymph nodes (LNs) of HCC after hepatic resection. The purpose of this study was to evaluate the expression of CK19 in primary liver tumor and regional LNs of HCC with and without lymph node metastasis (LNM).
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A dimensional approach to the phantom vibration and ringing syndrome during medical internship.
J Psychiatr Res
PUBLISHED: 05-19-2013
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Phantom vibrations and ringing of mobile phones are prevalent hallucinations in the general population. They might be considered as a "normal" brain mechanism. The aim of this study was to determine if a dimensional approach to identify individuals suffering from these hallucinations was more important than a categorical approach. A prospective longitudinal study of 74 medical interns (male: 46, mean age: 24.8 ± 1.2) was carried out using repeated investigations of the severity of phantom vibrations and ringing, as well as accompanying symptoms of anxiety and depression as measured by Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) before, at the 3rd, 6th, and 12th month during internship, and 2 weeks after internship. We utilized the cognitive and somatic subscales of the BDI, as well as the subjective, somatic and panic subscales of the BAI. The correlation between phantom vibration and ringing was lowest before the internship but became moderate during the internship and high 2 weeks after it. Compared to interns with subclinical phantom ringing and vibrations, interns with severe phantom vibrations and ringing had higher subjective and somatic anxiety and somatic depressive scores at any time point throughout the internship. Only interns with severe phantom ringing had more cognitive/affective depression. A dimensional approach to the phantom vibration and ringing syndrome is a powerful way to identify their correlation, as well as their association with anxiety and depression.
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The impact of trans-regulation on the evolutionary rates of metazoan proteins.
Nucleic Acids Res.
PUBLISHED: 05-08-2013
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Transcription factor (TF) and microRNA (miRNA) are two crucial trans-regulatory factors that coordinately control gene expression. Understanding the impacts of these two factors on the rate of protein sequence evolution is of great importance in evolutionary biology. While many biological factors associated with evolutionary rate variations have been studied, evolutionary analysis of simultaneously accounting for TF and miRNA regulations across metazoans is still uninvestigated. Here, we provide a series of statistical analyses to assess the influences of TF and miRNA regulations on evolutionary rates across metazoans (human, mouse and fruit fly). Our results reveal that the negative correlations between trans-regulation and evolutionary rates hold well across metazoans, but the strength of TF regulation as a rate indicator becomes weak when the other confounding factors that may affect evolutionary rates are controlled. We show that miRNA regulation tends to be a more essential indicator of evolutionary rates than TF regulation, and the combination of TF and miRNA regulations has a significant dependent effect on protein evolutionary rates. We also show that trans-regulation (especially miRNA regulation) is much more important in human/mouse than in fruit fly in determining protein evolutionary rates, suggesting a considerable variation in rate determinants between vertebrates and invertebrates.
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Clear-cell variant of calcifying epithelial odontogenic tumor (Pindborg tumor) in the mandible.
Int J Oral Sci
PUBLISHED: 04-22-2013
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We present an uncommon case (female patient aged 59 years) of the clear-cell variant of calcifying epithelial odontogenic tumor (CEOT) (also known as Pindborg tumor) in the mandible. The clinical characteristics and probable origins of the clear tumor cells of previously reported cases of clear-cell variant of intraosseous CEOT are also summarized and discussed.
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Absolute hypoxic exercise training enhances in vitro thrombin generation by increasing procoagulant platelet-derived microparticles under high shear stress in sedentary men.
Clin. Sci.
PUBLISHED: 03-26-2013
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HS (high shear) stress associated with artery stenosis facilitates TG (thrombin generation) by increasing the release of procoagulant PDMPs (platelet-derived microparticles). Physical exercise and hypoxia may paradoxically modulate vascular thrombotic risks. The aim of the present study was to investigate how exercise training with/without hypoxia affected TG mediated by PDMPs under physio-pathological shear flows. A total of 75 sedentary males were randomly divided into five groups (n=15 in each group): 21% O2 [NC (normoxic control)] or 15% O2 [HC (hypoxic control)] at rest or were trained at 50% of peak work rate under 21% O2 [NT (normoxic training)] or 15% O2 [HAT (hypoxic-absolute training)], or 50% of HR (heart rate) reserve under 15% O2 [HRT (hypoxic-relative training)] for 30 min/day, 5 days/week for 4 weeks. The PDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, strenuous exercise markedly increased the PDMP count (14.8%) and TG rate (19.5%) in PDMP-rich plasma at 100 dynes/cm2 of shear stress (P<0.05). After the interventions, both NT and HRT significantly attenuated the enhancement of HS-induced PDMPs (4.7 and 4.9%) and TG rate (3.8 and 3.0%) (P<0.05) by severe exercise. Conversely, HAT notably promoted the PDMP count (37.3%) and TG rate (38.9%) induced by HS (P<0.05), concurrent with increasing plasma TF (tissue factor) and coagulation factor V levels at rest or following exercise. We conclude that both HRT and NT depress similarly HS-mediated TG during exercise, but HAT accelerates the prothrombotic response to vigorous exercise. These findings provide new insights into how exercise training under a hypoxic condition influences the risk of thrombosis associated with stenotic arteries.
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Continuous intra-arterial chemotherapy for downstaging locally advanced oral commissure carcinoma.
Head Neck
PUBLISHED: 03-22-2013
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The purpose of this study was to assess the usefulness, safety, and efficacy of intra-arterial (IA) infusion chemotherapy for patients with locally advanced oral commissure cancer.
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Altered T-bet dominance in IFN-?-decoupled CD4+ T cells with attenuated cytokine storm and preserved memory in influenza.
J. Immunol.
PUBLISHED: 03-18-2013
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Cytokine storm has been postulated as one of the major causes of mortality in patients with severe respiratory viral infections such as influenza. With the help of an influenza Ag- specific mouse experimental system, we report that CD4(+) T cells contribute effector cytokines leading to lung inflammation in acute influenza. Although virus can no longer be detected from tissues 14 d postinfection, virus-derived Ag continues to drive a CD4(+) T cell response after viral clearance. Ag-specific CD4(+) T cells proliferate and evolve into memory CD4(+) T cells efficiently, but the production of effector cytokines is seriously hampered during this phase. This decoupling of proliferation and effector cytokine production doesnt appear in conjunction with increased suppression by regulatory T cells or decreased induction of transcription factors. Rather, GATA-3 and ROR-?t levels are elevated when compared with cells that have effector cytokine production. T-bet dominance over GATA-3 and ROR-?t decreases with the disarmament of effector cytokine production. Importantly, upon reinfection, these decoupled cells produce elevated levels of IFN-? and were effective in virus eradication. These results provide a mechanism through altered T-bet dominance to dampen the cytokine storm without impeding the generation of memory T cells in influenza virus infection.
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Eicosapentaenoic acid attenuated oxidative stress-induced cardiomyoblast apoptosis by activating adaptive autophagy.
Eur J Nutr
PUBLISHED: 02-18-2013
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Recently, several large, randomized clinical trials have proven the benefits of eicosapentaenoic acid (EPA) in cardiovascular prevention. However, the precise protective mechanisms of EPA for heart disease are still controversial. In this study, we evaluate the possible protective effects of EPA, especially the role of autophagy, against cardiomyocyte apoptosis induced by oxidative stress.
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Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling.
BMC Complement Altern Med
PUBLISHED: 02-12-2013
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Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation.
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pH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors.
Biomaterials
PUBLISHED: 02-07-2013
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Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(?-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.
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Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds.
Evid Based Complement Alternat Med
PUBLISHED: 02-06-2013
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Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, ?-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed.
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Tpl2 inhibitors thwart endothelial cell function in angiogenesis and peritoneal dissemination.
Neoplasia
PUBLISHED: 02-05-2013
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Angiogenesis is critical in the development of cancer, which involves several angiogenic factors in its peritoneal dissemination. The role of protein tumor progression locus 2 (Tpl2) in angiogenic factor-related endothelial cell angiogenesis is still unclear. To understand the precise mechanism(s) of Tpl2 inhibition in endothelial cells, this study investigated the role of Tpl2 in mediating angiogenic signals using in vitro, in vivo, and ex vivo models. Results showed that inhibition of Tpl2 inhibitor significantly reduced peritoneal dissemination in a mouse model by positron emission tomography/computed tomography imaging. Simultaneously, inhibiting Tpl2 blocked angiogenesis in tumor nodules and prevented angiogenic factor-induced proliferating cell nuclear antigen (PCNA) in endothelial cells. Vascular endothelial growth factor (VEGF) or chemokine (C-X-C motif) ligand 1 (CXCL1) increased Tpl2 kinase activity and phosphorylation in a dose- and time-dependent manner. Furthermore, Tpl2 inhibition or ablation by siRNA prevented the angiogenic signal-induced tube formation in Matrigel plug assay or aortic ring assay. Inhibiting Tpl2 also prevented the angiogenic factor-induced chemotactic motility and migration of endothelial cells. Tpl2 inhibition by CXCL1 or epidermal growth factor in endothelial cells was associated with inactivation of CCAAT/enhancer binding protein ?, nuclear factor ? light-chain enhancer of activated B cells, and activating protein 1 and suppression of VEGF expression. Thus, Tpl2 inhibitors thwart Tpl2-regulated VEGF by inactivating transcription factors involved in angiogenic factor-triggered endothelial cell angiogenesis. These results suggest that the therapeutic inhibition of Tpl2 may extend beyond cancer and include the treatment of other diseases involving pathologic angiogenesis.
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Change and predictors of symptom distress in breast cancer patients following the first 4 months after diagnosis.
J. Formos. Med. Assoc.
PUBLISHED: 02-04-2013
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Breast cancer patients may encounter a wide range of physical and psychosocial distress symptoms during diagnosis, while awaiting treatment, and during treatment. This study of newly diagnosed breast cancer patients explores: (1) changes in symptom distress over 4 months; and (2) factors predicting changes in symptom distress.
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Gender differences in cardiac autonomic modulation during medical internship.
Psychophysiology
PUBLISHED: 01-25-2013
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Medical internship is known to be a time of high stress and long working hours, which increases the risk of depression and cardiovascular disease. Gender differences in medical interns cardiovascular risk have not been reported previously. Thirty-eight medical interns (29 males) were repeatedly tested for depressive symptoms using the Hospital Anxiety and Depression Scale and 5-min spectral analysis of heart rate variability (HRV) at 3-month intervals during their internship. Among the male interns, the variance of the heart rate decreased at 6, 9, 12 months, and a reduced high frequency, which suggests reduced cardiac parasympathetic modulation, was found at 9 and 12 months into their internship. Increased depressive symptoms were also identified at 12 months in the male group. No significant differences in depression or any of the HRV indices were identified among the female interns during their internship.
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Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas during pregnancy.
Obstet Gynecol
PUBLISHED: 01-25-2013
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Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas is an unusual complication during pregnancy.
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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.