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Find video protocols related to scientific articles indexed in Pubmed.
Combining VCP Inhibition and SAHA Treatment Additively Enhances the Folding, Trafficking, and Function of Epilepsy-Associated GABAA Receptors.
J. Biol. Chem.
PUBLISHED: 11-20-2014
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Gamma-aminobutyric acid type A (GABAA) receptors are the primary inhibitory ion channels in the mammalian central nervous system. The A322D mutation in the ?1 subunit results in its excessive endoplasmic reticulum-associated degradation (ERAD) at the expense of plasma membrane trafficking, leading to autosomal dominant juvenile myoclonic epilepsy. Presumably, VCP/p97 extracts misfolded subunits from the ER membrane to the cytosolic proteasome for degradation. Here, we showed that inhibiting VCP using Eeyarestatin I reduces the ERAD of the ?1(A322D) subunit without an apparent effect on its dynamin-1 dependent endocytosis, and this treatment enhances its trafficking. Furthermore, co-application of Eeyarestatin I and SAHA (suberanilohydroxamic acid), a known small molecule that promotes chaperone-assisted folding, yields an additive restoration of surface expression of ?1(A322D) subunits in HEK293 cells and neuronal SH-SY5Y cells. Consequently, this combination significantly increases GABA-induced chloride currents in whole-cell patch clamping experiments than either chemical compound alone in HEK293 cells. Our findings suggest that VCP inhibition without stress induction together with folding enhancement represents a new strategy to restore proteostasis of misfolding-prone GABAA receptors, and thus a potential remedy for idiopathic epilepsy.
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Synthesis and Herbicidal Evaluation of Triketone-containing Quinazoline-2,4-diones.
J. Agric. Food Chem.
PUBLISHED: 11-19-2014
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Exploring novel 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) inhibitors is one of the most promising research directions in herbicide discovery. To discover new triketone herbicides with broad-spectrum weed control as well as the excellent crop selectivity, a series of (total 52) novel triketone-containing quinazoline-2,4-dione derivatives were synthesized and further bio-evaluated. The greenhouse testing indicated that many of newly synthesized compounds showed better or the excellent herbicidal activity against broadleaf and monocotyledonous weeds at the dosages of 37.5-150 g ai/ha. The structure and activity relationship in this study indicated that triketone-containing quinazoline-2, 4-dione motif has possessed a great impact on herbicide activity and may be utilized for further optimization. Among the new compounds, III-b and VI-a~d displayed broader spectrum of weed control than mesotrione. In addition, the compound III-b also demonstrated comparatively superior crop selectivity to mesotrione, thus possessing a great potential for weed control in field.
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Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium-induced colitis in mice.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 10-15-2014
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Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) and increases the risk of the development of colorectal carcinoma. The anti-inflammatory and immunomodulatory properties of mesenchymal stem cells (MSCs) make them promising tools for treating immune-mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSCs has hampered the use of bone marrow and umbilical cord blood derived MSCs in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly derived umbilical MSCs (UMSCs) on dextran sulfate sodium (DSS) induced colitis in mice. The severity of colitis in mice was assessed using body weight loss, stool consistency, rectal bleeding, colon shortening, and hematological parameters. Colonic myeloperoxidase (MPO) and proinflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly derived UMSCs significantly diminished the severity of colitis, reduced histolopathological score, and decreased MPO activity and cytokines levels. Furthermore, the UMSCs markedly decreased the expression of COX2 and iNOS in the colon. In addition, transplantation of UMSCs reduced intestinal permeability and up-regulated the expression of tight junction proteins. These results indicate the anti-inflammation and regulation of tight junction proteins by Wharton's jelly derived UMSCs ameliorates colitis. This article is protected by copyright. All rights reserved.
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Threonine and tryptophan supplementation enhance porcine respiratory and reproductive syndrome (PRRS) vaccine-induced immune responses of growing pigs.
Anim. Sci. J.
PUBLISHED: 09-03-2014
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The aim of the present study was to investigate influences of threonine and tryptophan supplementation (TTS) on immune response of growing pigs inoculated with modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Twenty growing barrows (Landrace?×?Yorkshire) were randomly assigned to four groups according to the PRRS vaccination and TTS. Serum samples were collected from all pigs at days 0, 7, 14, 21, 28, 35, 49 post-vaccination (day 0 defined as the day of vaccination). Pigs were euthanized and samples collected at day 49 post-vaccination. The results showed that TTS tended to increase weight gain and average daily gain (ADG) of pigs (P?
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Design, synthesis and herbicidal activity of novel quinazoline-2,4-diones as 4-hydroxyphenylpyruvate dioxygenase inhibitors.
Pest Manag. Sci.
PUBLISHED: 09-03-2014
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4-Hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27) has been identified as one of the most promising target sites for herbicide discovery. To discover novel HPPD inhibitors with high herbicidal activity and improved crop selectivity, a series of novel triketone-containing quinazoline-2,4-dione derivatives possessing a variety of substituents at the N-1 position of the quinazoline-2,4-dione ring were designed and synthesised.
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Identifying candidate genes for discrimination of ulcerative colitis and Crohn's disease.
Mol. Biol. Rep.
PUBLISHED: 09-03-2014
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In this study we aimed to screen effective biomarkers for differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). By using the gene expression profile dataset GSE24287 including 47 ileal CD, 27 UC and 25 non-inflammatory bowel diseases control downloaded from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between UC patients and controls as well as between CD patients and controls (|log2FC(fold change)| > 1 and p < 0.05). Then Gene Ontology (GO) functional enrichment analyses were performed for these DEGs in two groups, followed by the construction of weight PPI (protein-protein interaction) networks. Subnets enriched for the PPIs and differentially expressed genes were constructed based on the weight PPI networks. The overlapping genes between the genes in the top 10 subnets with smallest p value and the DEGs were selected as the candidate genes of disease. A total of 75 DEGs were identified in UC group and 87 ones in CD group. There were 69 and 57 specific DEGs in CD group and UC group, respectively. The DEGs in CD group were mainly enriched in "inflammatory response" and "defense response", while the most significantly enriched GO terms in UC group were "anion transport" and "chemotaxis". FOS and SOCS3 were identified as candidate genes for CD and other three genes HELB, ZBTB16 and FAM107A were candidate genes for UC. In conclusion, there were distinct genetic alterations between UC and CD. The candidate genes identified in current study may be used as biomarkers for differential diagnosis of CD and UC.
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Polyamine Depletion Attenuates Isoproterenol-Induced Hypertrophy and Endoplasmic Reticulum Stress in Cardiomyocytes.
Cell. Physiol. Biochem.
PUBLISHED: 09-01-2014
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Background/Aim: Polyamines (putrescine, spermidine and spermine) play an essential role in cell growth, differentiation and apoptosis. Hypertrophy is accompanied by an increase in polyamine synthesis and endoplasmic reticulum stress (ERS) in cardiomyocytes. The present study was undertaken to elucidate the molecular interactions between polyamines, ERS and cardiac hypertrophy. Methods: Myocardial hypertrophy was simulated by incubating cultured neonatal rat cardiomyocytes in 100 nM isoproterenol (ISO). Polyamine deletion was achieved using 0.5 mM difluoromethylornithine (DFMO). Hypertrophy was estimated using cell surface area measurements, total protein concentrations and atrial natriuretic peptide (ANP) gene expression. Apoptosis was measured using flow cytometry and transmission electron microscopy. Expression of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) were analyzed via real-time PCR and Western blotting. Protein expression of ERS and apoptosis factors were analyzed using Western blotting. Results: DFMO (0.5 mM and 2 mM) treatments significantly attenuated hypertrophy and apoptosis induced by ISO in cardiomyocytes. DFMO also decreased lactate dehydrogenase (LDH) and malondialdehyde (MDA) level in the culture medium. In addition, DFMO (0.5 mM) down regulated the expression of ODC, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and Bax and up regulated the expression of SSAT and Bcl-2. Finally, these changes were partly reversed by the addition of exogenous putrescine (0.5 mM). Conclusion: The data presented here suggest that polyamine depletion could inhibit cardiac hypertrophy and apoptosis, which is closely related to the ERS pathway. © 2014 S. Karger AG, Basel.
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Macronutrients intake and risk of Parkinson's disease: A meta-analysis.
Geriatr Gerontol Int
PUBLISHED: 08-28-2014
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We carried out a meta-analysis to summarize the evidence from published studies on macronutrients intake and risk of Parkinson's disease (PD).
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Recombinant porcine epidermal growth factor-secreting Lactococcus lactis promotes the growth performance of early-weaned piglets.
BMC Vet. Res.
PUBLISHED: 08-21-2014
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Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets' production.
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Pyrazolone-quinazolone hybrids: a novel class of human 4-hydroxyphenylpyruvate dioxygenase inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 08-18-2014
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4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting 4-hydroxyphenylpyruvate acid to homogentisate, is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism. However, only one commercial drug, NTBC, also known as nitisinone, has been available for clinical use so far. Herein, we have elucidated the structure-based design of a series of pyrazolone-quinazolone hybrids that are novel potent human HPPD inhibitors through the successful integration of various techniques including computational simulations, organic synthesis, and biochemical characterization. Most of the new compounds displayed potent inhibitory activity against the recombinant human HPPD in nanomolar range. Compounds 3h and 3u were identified as the most potent candidates with Ki values of around 10 nM against human HPPD, about three-fold more potent than NTBC. Molecular modeling indicated that the interaction between the pyrazolone ring and ferrous ion, and the hydrophobic interaction of quinazolone with its surrounding residues, such as Phe347 and Phe364, contributed greatly to the high potency of these inhibitors. Therefore, compounds 3h and 3u could be potentially useful for the treatment of type I tyrosinemia and other diseases with defects in tyrosine degradation.
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Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer advanced-stage diagnosis in Texas.
Womens Health Issues
PUBLISHED: 08-12-2014
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Advanced-stage diagnosis is among the primary causes of mortality among cervical cancer patients. With the wide use of Pap smear screening, cervical cancer advanced-stage diagnosis rates have decreased. However, disparities of advanced-stage diagnosis persist among different population groups. A challenging task in cervical cancer disparity reduction is to identify where underserved population groups are.
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Effects of dietary threonine and tryptophan supplementation on growing pigs induced by porcine respiratory and reproductive syndrome vaccination.
Arch Anim Nutr
PUBLISHED: 08-12-2014
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A total of 32 growing pigs were used in a 2 × 2 factorial arrangement of treatments with two different diets (conventional [CON] diet vs. threonine [Thr]- and tryptophan [Trp]-rich [TTR] diet) and two immunological challenge regimens (porcine respiratory and reproductive syndrome [PRRS] vaccine vs. phosphate buffer solution [PBS]) to study the hypothesis that dietary supplementation with Trp and Thr would benefit for growing pigs vaccinated with PRRS vaccine. After feeding the experimental diets for 21 d, the pigs were intramuscularly vaccinated with PRRS or PBS. Performance data were recorded over a period of 10 weeks and are presented for the pre-challenge period (3 weeks) and the challenge period (7 weeks, where on day 1, pigs were immunologically challenged). During the pre-challenge period, the growth performance was not different between dietary treatments. PRRS vaccination resulted in increased rectal temperature and decreased feed intake and growth rate (p < 0.05). In PRRS-vaccinated pigs, diet TTR enhanced the feed intake, especially during the first 2 weeks after the PRRS vaccination compared with diet CON (p < 0.05). PRRS vaccination also resulted in increased plasma concentration of urea nitrogen, essential and non-essential amino acids (p < 0.05) and porcine reproductive and respiratory syndrome virus specific antibodies (p < 0.05), but decreased concentration of immunoproteins including alpha-1-acylglycoprotein and immunoglobulin G (p < 0.05). The alleviation of the PRRS vaccination induced decrease in feed intake and growth rate by Thr and Trp supplementation, indicating that the PRRS-vaccinated pigs had a higher Thr and Trp requirement than non-vaccinated pigs.
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CD45 ligation expands Tregs by promoting interactions with DCs.
J. Clin. Invest.
PUBLISHED: 08-06-2014
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Regulatory T cells (Tregs), which express CD4 and FOXP3, are critical for modulating the immune response and promoting immune tolerance. Consequently, methods to expand Tregs for therapeutic use are of great interest. While transfer of Tregs after massive ex vivo expansion can be achieved, in vivo expansion of Tregs would be more practical. Here, we demonstrate that targeting the CD45 tyrosine phosphatase with a tolerogenic anti-CD45RB mAb acutely increases Treg numbers in WT mice, even in absence of exogenous antigen. Treg expansion occurred through substantial augmentation of homeostatic proliferation in the preexisting Treg population. Moreover, anti-CD45RB specifically increased Treg proliferation in response to cognate antigen. Compared with conventional T cells, Tregs differentially regulate their conjugation with DCs. Therefore, we determined whether CD45 ligation could alter interactions between Tregs and DCs. Live imaging showed that CD45 ligation specifically reduced Treg motility in an integrin-dependent manner, resulting in enhanced interactions between Tregs and DCs in vivo. Increased conjugate formation, in turn, augmented nuclear translocation of nuclear factor of activated T cells (NFAT) and Treg proliferation. Together, these results demonstrate that Treg peripheral homeostasis can be specifically modulated in vivo to promote Treg expansion and tolerance by increasing conjugation between Tregs and DCs.
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IL-12 regulates B7-H1 expression in ovarian cancer-associated macrophages by effects on NF-?B signalling.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-02-2014
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B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms.
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Bias correction for selecting the minimal-error classifier from many machine learning models.
Bioinformatics
PUBLISHED: 08-01-2014
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Supervised machine learning is commonly applied in genomic research to construct a classifier from the training data that is generalizable to predict independent testing data. When test datasets are not available, cross-validation is commonly used to estimate the error rate. Many machine learning methods are available, and it is well known that no universally best method exists in general. It has been a common practice to apply many machine learning methods and report the method that produces the smallest cross-validation error rate. Theoretically, such a procedure produces a selection bias. Consequently, many clinical studies with moderate sample sizes (e.g. n = 30-60) risk reporting a falsely small cross-validation error rate that could not be validated later in independent cohorts.
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Changes in plasma amino acid profiles, growth performance and intestinal antioxidant capacity of piglets following increased consumption of methionine as its hydroxy analogue.
Br. J. Nutr.
PUBLISHED: 08-01-2014
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The aim of the present study was to determine whether early weaning-induced growth retardation could be attenuated by increased consumption of methionine as DL-methionine (DLM) or DL-2-hydroxy-4-methylthiobutyrate (HMTBA) in both lactating sows and weaned piglets. Therefore, diets containing DLM and HMTBA at 25% of the total sulphur-containing amino acids (AA) present in the control (CON) diet were fed to lactating sows and weaned piglets and their responses were evaluated. Compared with the CON diet-fed sows, the HMTBA diet-fed sows exhibited a tendency (P<0·10) towards higher plasma taurine concentrations and the DLM diet-fed sows had higher (P<0·05) plasma taurine concentrations, but lower (P<0·05) isoleucine concentrations. Suckling piglets in the HMTBA treatment group had higher (P<0·05) intestinal reduced glutathione (GSH) content, lower (P<0·05) oxidised glutathione (GSSG):GSH ratio, and higher (P<0·05) plasma cysteine and glutathione peroxidase (GPx) activity than those in the CON and DLM treatment groups. The feed intake (P<0·05) and body weight of piglets averaged across post-weaning (PW) days were higher (P< 0·05) in the HMTBA treatment group than in the DLM treatment group and were higher (P<0·05) and tended (P<0·10) to be higher, respectively, in the HMTBA treatment group than in the CON treatment group. Increased (P<0·05) GSSG content and GSSG:GSH ratio and down-regulated (P<0·05) expression of nutrient transport genes were observed in the jejunum of piglets on PW day 7 than on PW day 0. On PW day 14, the HMTBA diet-fed piglets had higher (P<0·05) intestinal GSH content than the CON diet-fed piglets and higher (P<0·05) plasma GPx activity, villus height and goblet cell numbers than the CON diet- and DLM diet-fed piglets. In conclusion, early weaning-induced growth retardation appears to be attenuated through changes in plasma AA profiles and elevation of growth performance and intestinal antioxidant capacity in piglets following increased consumption of methionine as HMTBA.
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Demonstration of an add-on effect of probucol and cilostazol on the statin-induced anti-atherogenic effects.
Histol. Histopathol.
PUBLISHED: 07-31-2014
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Statins are often prescribed for treatment of cardiovascular diseases, although there are still many patients who cannot be effectively treated by statins alone. Both probucol and cilostazol exhibit anti-atherogenic effects. In the current study, we attempted to investigate whether a probucol and cilostazol combination had any add-on effects on atorvastatin. To examine this hypothesis, we fed Japanese white rabbits with a cholesterol-rich diet supplemented with atorvastatin alone (Statin group), probucol and cilostazol (PC group), atorvastatin, probucol and cilostazol (APC group), and compared their effects on plasma lipids and aortic atherosclerosis. All three drug-treated groups had lowered total cholesterol levels compared with the vehicle group but high-density lipoproteins cholesterol levels of the atorvastatin group were higher than other groups. Although aortic atherosclerosis was significantly reduced in all drug-treated groups, the most prominent atheroprotective effect was seen in APC group (APC: 67% reduction? PC: 43% reduction? Statin group: 42% reduction over the vehicle). Morphometric analysis revealed that the reduced aortic atherosclerosis in all three groups was mainly attributed to the reduction of intimal macrophages and smooth muscle cells. These results suggest that a combination of probucol and cilostazol with statin enhances statin's anti-atherogenic functions, which may be beneficial for those patients who are less responsive to statin therapy alone.
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Elemene injection induced autophagy protects human hepatoma cancer cells from starvation and undergoing apoptosis.
Evid Based Complement Alternat Med
PUBLISHED: 07-24-2014
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Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anticancer effects against a broad spectrum of tumors. In an in vivo experiment, we found that apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2, combined with elemene injection (Ele) for the treatment of H22 solid tumor in mice resulted in worse effectiveness than apatinib alone. Moreover, Ele could protect HepG2 cells from death induced by serum-free starvation. Further data on the mechanism study revealed that Ele induced protective autophagy and prevented human hepatoma cancer cells from undergoing apoptosis. Proapoptosis effect of Ele was enhanced when proautophagy effect was inhibited by hydroxychloroquine. Above all, Ele has the effect of protecting cancer cells from death either in apatinib induced nutrient deficient environment or in serum-free induced starvation. A combination of elemene injection with autophagy inhibitor might thus be a useful therapeutic option for hepatocellular carcinoma.
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Direct detection of FoxP3 expression in thymic double-negative CD4-CD8- cells by flow cytometry.
Sci Rep
PUBLISHED: 07-03-2014
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Foxp3 expression is a marker of regulatory T cells (Treg), but how early it is expressed in the thymus is still not fully defined. In this study, we examined Foxp3 expression in double-negative (DN) CD4(-)CD8(-) T cell precursors in the thymus by flow cytometry. By increasing the number of collected cells from the conventional 10(4) cells up to more than 10(6) cells during flow cytometry, we found that DN cells exhibited higher Foxp3 expression than double-positive (DP) CD4(+)CD8(+) and single-positive (SP) CD4(+) or CD8(+) (SP) T cells. CD44(+) expression positively correlated with Foxp3 in thymic DN cells. Furthermore, TCR-?(-)CD25(+) DN cells exhibited the highest frequency of Foxp3-expressing cells. Almost all Foxp3(+) cells expressed CD25in DN cells. These results suggest that Foxp3 expression in DN cells can directly be detected by flow cytometry and it was positively corelated with CD25 and CD44 in DN cells.
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Exercise training preserves ischemic preconditioning in aged rat hearts by restoring the myocardial polyamine pool.
Oxid Med Cell Longev
PUBLISHED: 07-02-2014
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Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool. Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol. Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, ?-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro. Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.
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Geographic variations of racial/ethnic disparities in cervical cancer mortality in Texas.
South. Med. J.
PUBLISHED: 06-18-2014
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To examine how racial/ethnic disparities of cervical cancer mortality vary geographically and to identify factors contributing to the variation.
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FHL1C induces apoptosis in Notch1-dependent T-ALL cells through an interaction with RBP-J.
BMC Cancer
PUBLISHED: 06-17-2014
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Aberrantly activated Notch signaling has been found in more than 50% of patients with T-cell acute lymphoblastic leukemia (T-ALL). Current strategies that employ ?-secretase inhibitors (GSIs) to target Notch activation have not been successful. Many limitations, such as non-Notch specificity, dose-limiting gastrointestinal toxicity and GSI resistance, have prompted an urgent need for more effective Notch signaling inhibitors for T-ALL treatment. Human four-and-a-half LIM domain protein 1C (FHL1C) (KyoT2 in mice) has been demonstrated to suppress Notch activation in vitro, suggesting that FHL1C may be new candidate target in T-ALL therapy. However, the role of FHL1C in T-ALL cells remained unclear.
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An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders.
Cytokine Growth Factor Rev.
PUBLISHED: 06-05-2014
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Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future.
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Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-30-2014
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To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).
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Prevalence of extended treatment in pulmonary tuberculosis patients receiving first-line therapy and its association with recurrent tuberculosis in Beijing, China.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 05-25-2014
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In China, it is known that extended treatment is given to patients with pulmonary TB after they have successfully completed 6 months of first-line treatment. This practice is not officially reported to the National Tuberculosis Control Programme, so there are no data on its prevalence, its possible benefits in terms of preventing recurrent disease or the costs. This study aimed to provide information, from a single TB dispensary in Beijing, China, on the prevalence of extended anti-TB treatment and its relationship with recurrent TB.
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Distinct age-matched serum biomarker profiles in patients with cutaneous T-cell lymphoma.
Exp. Dermatol.
PUBLISHED: 05-23-2014
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Immunological functions decline with age. Because MS/SzS predominately affects the elderly, it is important to distinguish age-related from cancer-specific changes. Also, MF and SzS are malignancies of CD4(+) T-lymphocytes, further compromising an immune state of the patients. The objectives of this study were to distinguish disease-specific immunological deterioration by performing comparative age-matched Luminex multiplex assessment of 34 serum biomarkers between patients with MF/SzS, HIV-infected individuals and normal controls. Controlling for age, expression level appears to significantly differ between patients with MF/SzS and controls for the following biomarkers: G-CSF, IL-5, MIP-1?, TNF-?, VEGF, EOTAXIN, IL-8, IL-12, IL-2R, IP10, MCP-1, MIG, TNFR1 and TNFR2 (P < 0.05), while others showed normal age-related changes. Interestingly, cluster analysis placed MF/SzS profiles closer to HIV. This further underscores an immunologically compromised state of patients with MF/SzS and suggests its potential self-perpetuating role in disease progression.
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Dermo-glandular flap for treatment of recurrent periductal mastitis.
J. Surg. Res.
PUBLISHED: 05-20-2014
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Recurrent periductal mastitis (PDM) is usually refractory to medical treatment and normally requires surgical intervention or even mastectomy. This study aimed to evaluate the effectiveness and safety of extended excision with transferring a random breast dermo-glandular flap (BDGF) in the treatment of severe PDM.
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Mouse dead end 1-? interacts with c-Jun and stimulates activator protein 1 transactivation.
Mol Med Rep
PUBLISHED: 05-16-2014
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Dead end 1 (Dnd1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with dnd1-?. The interaction between Dnd1-? and c-Jun was demonstrated to occur by glutathione S?transferase pull?down and co-immunoprecipitation. Using confocal microscopy, Dnd1-? was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, Dnd1-? and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with Dnd1-? and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with dnd1-? facilitates the investigation of the functions and molecular mechanisms of Dnd1.
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Recognition of Protein-coding Genes Based on Z-curve Algorithms.
Curr. Genomics
PUBLISHED: 05-14-2014
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Recognition of protein-coding genes, a classical bioinformatics issue, is an absolutely needed step for annotating newly sequenced genomes. The Z-curve algorithm, as one of the most effective methods on this issue, has been successfully applied in annotating or re-annotating many genomes, including those of bacteria, archaea and viruses. Two Z-curve based ab initio gene-finding programs have been developed: ZCURVE (for bacteria and archaea) and ZCURVE_V (for viruses and phages). ZCURVE_C (for 57 bacteria) and Zfisher (for any bacterium) are web servers for re-annotation of bacterial and archaeal genomes. The above four tools can be used for genome annotation or re-annotation, either independently or combined with the other gene-finding programs. In addition to recognizing protein-coding genes and exons, Z-curve algorithms are also effective in recognizing promoters and translation start sites. Here, we summarize the applications of Z-curve algorithms in gene finding and genome annotation.
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[Trastuzumab administered concurrently with anthracycline-containing adjuvant regimen for breast cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 05-07-2014
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To investigate the safety and efficacy of trastuzumab administered concurrently with anthracycline-containing adjuvant regimen for breast cancer.
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Comparative effects of sodium butyrate and flavors on feed intake of lactating sows and growth performance of piglets.
Anim. Sci. J.
PUBLISHED: 04-29-2014
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We examined the effects of sodium butyrate and flavors on feed intake of lactating sows and growth performance of piglets. A total of 52 primiparous sows (Large White) were randomly divided into four treatments (n?=?13) and received 6?g/kg sodium butyrate (SB), fruit-milk (FM) flavor and fruit-milk-anise (FMA) flavor with pair feeding to the mothers receiving the control diet. The feeding trial lasted for 29 days, including 21 days of nursing and 8 days of post-weaning period, respectively. The nursing and weaning piglets received creep diets with the same flavor or SB supplement as their mother. The results showed that FMA flavor increased average daily feed intake (ADFI) of lactating sows (P?
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A novel method for tinidazole detection using Mn-modified CdSe/CdS quantum dots as a luminescent probe.
J Nanosci Nanotechnol
PUBLISHED: 04-17-2014
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A new method for the determination of tinidazole based on the fluorescence quenching of citrate-capped Mn-modified CdSe/CdS quantum dots was developed. In aqueous solution, the fluorescence of the quantum dots at 610 nm was quenched gradually with the increase of the concentration of tinidazole. Based on this, a simple, fast, low-cost and specific quantitative method for tinidazole detection was set up. Under optimal conditions, a good linearity was built between the fluorescence quenching of Mn-modified CdSe/CdS quantum dots and the concentration of tinidazole in the range of 4-400 microM with a correlation coefficient of 0.9998. The limit of detection (3sigma/K) was 0.4 microM. The proposed method was applied to the detections of tinidazole in tablets and injections with satisfactory results.
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The various architectures and properties of a series of coordination polymers tuned by the central metals.
Dalton Trans
PUBLISHED: 04-10-2014
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Five new metal-organic coordination polymers based on the mixed ligands of a semi-rigid bis-pyridyl-bis-amide N,N'-bis(3-pyridinecarboxamide)-1,2-cyclohexane (3-bpah) and 1,4-benzenedicarboxylic acid (1,4-H2BDC), namely [Co(3-bpah)(1,4-BDC)(H2O)3] (1), [Ni(3-bpah)(1,4-BDC)(H2O)3] (2), [Cu(3-bpah)(1,4-BDC)] (3), [Zn(3-bpah)(1,4-BDC)]·H2O (4) and [Cd(3-bpah)(1,4-BDC)(H2O)] (5), have been hydrothermally synthesized and structurally characterized. Complexes 1 and 2 are isostructural and display the similar 1D infinite chains, which are further linked via hydrogen-bonding interactions to generate 3D supramolecular frameworks. Complex 3 features a 3D polymeric framework with CdSO4-like topology. Complexes 4 and 5 show two similar 2D (2,4)-connected networks with (4·8(5))(4) topology, in which the 3-bpah ligands adopt different ?2-bridging coordination modes via the ligation of two pyridyl nitrogen atoms in 4 and via the ligation of one pyridyl nitrogen and one amide oxygen atom in 5. In addition, the central metals show different coordination geometries in 4 and 5. The adjacent layers of complexes 4 and 5 are finally extended into 3D supramolecular architectures through hydrogen-bonding interactions. The effects of the central metals on the structures and properties of complexes 1-5 have been discussed. The electrochemical properties of complexes 1-3 and fluorescent sensing behaviors of 4-5 toward ethanol and nitrobenzene have been investigated in detail.
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Effects of maternal over- and undernutrition on intestinal morphology, enzyme activity, and gene expression of nutrient transporters in newborn and weaned pigs.
Nutrition
PUBLISHED: 04-03-2014
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It has been suggested that maternal nutrition during gestation is involved in the offspring's intestinal development. The aim of this study was to evaluate the effects of maternal nutrition on digestive and absorptive function of offspring at both birth and weaning with pig as model.
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Five regulatory genes detected by matching signatures of eQTL and GWAS in psoriasis.
J. Dermatol. Sci.
PUBLISHED: 04-02-2014
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Psoriasis is a common immune-mediated inflammatory skin disease with strong genetic dispositions. Although more than 40 susceptibility loci have been revealed mostly through psoriasis genome wide association studies, genetic variants with small effect remain to be identified.
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Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.
Mol. Biol. Rep.
PUBLISHED: 03-21-2014
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People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ? 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor ?, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.
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Novel shikonin derivatives targeting tubulin as anticancer agents.
Chem Biol Drug Des
PUBLISHED: 03-20-2014
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In this study, we report the identification of a new shikonin-phenoxyacetic acid derivative, as an inhibitor of tubulin. A series of compounds were prepared; among them, compound 16 [(R) -1 - (5, 8- dihydroxy-1, 4- dioxo-1, 4- dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2- (4- phenoxyphenyl) acetate] potently inhibited the function of microtubules, inducing cell growth inhibition, apoptosis of cancer cell lines in a concentration and time-dependent manner. Molecular docking involving 16 at the vinblastine binding site of tubulin indicated that a phenoxy moiety interacted with tubulin via hydrogen bonding with asparaginate (Asn) and tyrosine (Tyr). Analysis of microtubules with confocal microscopy demonstrated that 16 altered the microtubule architecture and exhibited a significant reduction in microtubule density. Cell cycle assay further proved that HepG2 cells were blocked in G2/M phase. Our study provides a new, promising compound for the development of tubulin inhibitors by proposing a new target for the anticancer activity of shikonin.
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Missing value imputation in high-dimensional phenomic data: imputable or not, and how?
BMC Bioinformatics
PUBLISHED: 03-06-2014
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BackgroundIn modern biomedical research of complex diseases, a large number of demographic and clinical variables, herein called phenomic data, are often collected and missing values (MVs) are inevitable in the data collection process. Since many downstream statistical and bioinformatics methods require complete data matrix, imputation is a common and practical solution. In high-throughput experiments such as microarray experiments, continuous intensities are measured and many mature missing value imputation methods have been developed and widely applied. Numerous methods for missing data imputation of microarray data have been developed. Large phenomic data, however, contain continuous, nominal, binary and ordinal data types, which void application of most methods. Though several methods have been developed in the past few years, not a single complete guideline is proposed with respect to phenomic missing data imputation.ResultsIn this paper, we investigated existing imputation methods for phenomic data, proposed a self-training selection (STS) scheme to select the best imputation method and provide a practical guideline for general applications. We introduced a novel concept of ¿imputability measure¿ (IM) to identify missing values that are fundamentally inadequate to impute. In addition, we also developed four variations of K-nearest-neighbor (KNN) methods and compared with two existing methods, multivariate imputation by chained equations (MICE) and missForest. The four variations are imputation by variables (KNN-V), by subjects (KNN-S), their weighted hybrid (KNN-H) and an adaptively weighted hybrid (KNN-A). We performed simulations and applied different imputation methods and the STS scheme to three lung disease phenomic datasets to evaluate the methods. An R package ¿phenomeImpute¿ is made publicly available.ConclusionsSimulations and applications to real datasets showed that MICE often did not perform well; KNN-A, KNN-H and random forest were among the top performers although no method universally performed the best. Imputation of missing values with low imputability measures increased imputation errors greatly and could potentially deteriorate downstream analyses. The STS scheme was accurate in selecting the optimal method by evaluating methods in a second layer of missingness simulation. All source files for the simulation and the real data analyses are available on the author¿s publication website.
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Dasatinib promotes the expansion of a therapeutically superior T-cell repertoire in response to dendritic cell vaccination against melanoma.
Oncoimmunology
PUBLISHED: 02-27-2014
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Dasatinib (DAS) is a potent inhibitor of the BCR-ABL, SRC, c-KIT, PDGFR, and ephrin tyrosine kinases that has demonstrated only modest clinical efficacy in melanoma patients. Given reports suggesting that DAS enhances T cell infiltration into the tumor microenvironment, we analyzed whether therapy employing the combination of DAS plus dendritic cell (DC) vaccination would promote superior immunotherapeutic benefit against melanoma. Using a M05 (B16.OVA) melanoma mouse model, we observed that a 7-day course of orally-administered DAS (0.1 mg/day) combined with a DC-based vaccine (VAC) against the OVA257-264 peptide epitope more potently inhibited tumor growth and extended overall survival as compared with treatment with either single modality. The superior efficacy of the combinatorial treatment regimen included a reduction in hypoxic-signaling associated with reduced levels of immunosuppressive CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSC) and CD4(+)Foxp3(+) regulatory T (Treg) populations in the melanoma microenvironment. Furthermore, DAS + VAC combined therapy upregulated expression of Type-1 T cell recruiting CXCR3 ligand chemokines in the tumor stroma correlating with activation and recruitment of Type-1, vaccine-induced CXCR3(+)CD8(+) tumor-infiltrating lymphocytes (TILs) and CD11c(+) DC into the tumor microenvironment. The culmination of this bimodal approach was a profound "spreading" in the repertoire of tumor-associated antigens recognized by CD8(+) TILs, in support of the therapeutic superiority of combined DAS + VAC immunotherapy in the melanoma setting.
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Psychological intervention for postpartum depression.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 02-18-2014
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The postpartum depression outcome and the effect of psychological intervention were studied in order to reduce the occurrence and development of the postpartum depression. A survey of 4000 women within 4-6 weeks postpartum in 80 communities in Shenzhen, China was performed using random cluster sampling method. By employing Edinburgh Postnatal Depression Scale (EPDS) as a screening tool, the positive women (defined as EPDS ?10) were randomly divided into intervention group and control group at a ratio of 1:2. The women in the intervention group were treated by means of mailing postpartum depression prevention and treatment knowledge manual, face-to-face counseling, and telephone psychological counseling interventions aiming at individual risk factors, while those in the control group were treated with conventional methods. EPDS scores were assessed in these two groups again at 6th month postpartum. Totally, 3907 valid questionnaires were obtained. All the 771 positive women were divided into two groups: 257 in the intervention group, and 514 in the control group. At 6th month postpartum, the EPDS scores in the intervention group were decreased significantly, from baseline stage (12.84±3.02) to end stage (3.05±2.93), while EPDS scores in the control group were reduced from 12.44±2.78 to 6.94±4.02. There were significant differences in the EPDS scores at end stage between the two groups (t=13.059, P<0.001). Psychological intervention can reduce postpartum depression, with better maternal compliance. It is feasible and necessary to establish postpartum depression screening and psychological intervention model in community-hospital and include the postpartum depression screening, intervention, and follow-up into the conventional healthcare.
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New researches and application progress of commonly used optical molecular imaging technology.
Biomed Res Int
PUBLISHED: 02-17-2014
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Optical molecular imaging, a new medical imaging technique, is developed based on genomics, proteomics and modern optical imaging technique, characterized by non-invasiveness, non-radiativity, high cost-effectiveness, high resolution, high sensitivity and simple operation in comparison with conventional imaging modalities. Currently, it has become one of the most widely used molecular imaging techniques and has been applied in gene expression regulation and activity detection, biological development and cytological detection, drug research and development, pathogenesis research, pharmaceutical effect evaluation and therapeutic effect evaluation, and so forth, This paper will review the latest researches and application progresses of commonly used optical molecular imaging techniques such as bioluminescence imaging and fluorescence molecular imaging.
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Ultrasound-mediated local drug and gene delivery using nanocarriers.
Biomed Res Int
PUBLISHED: 02-14-2014
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With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.
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New progress in angiogenesis therapy of cardiovascular disease by ultrasound targeted microbubble destruction.
Biomed Res Int
PUBLISHED: 02-13-2014
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Angiogenesis plays a vital part in the pathogenesis and treatment of cardiovascular disease and has become one of the hotspots that are being discussed in the past decades. At present, the promising angiogenesis therapies are gene therapy and stem cell therapy. Besides, a series of studies have shown that the ultrasound targeted microbubble destruction (UTMD) was a novel gene delivery system, due to its advantages of noninvasiveness, low immunogenicity and toxicity, repeatability and temporal and spatial target specificity; UTMD has also been used for angiogenesis therapy of cardiovascular disease. In this review, we mainly discuss the combination of UTMD and gene therapy or stem cell therapy which is applied in angiogenesis therapy in recent researches, and outline the future challenges and good prospects of these approaches.
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Advance of molecular imaging technology and targeted imaging agent in imaging and therapy.
Biomed Res Int
PUBLISHED: 02-13-2014
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Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy.
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Integrated analysis of long non-coding RNAs and mRNA expression profiles reveals the potential role of lncRNAs in gastric cancer pathogenesis.
Int. J. Oncol.
PUBLISHED: 02-08-2014
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Long non-coding RNAs (lncRNAs) have been shown to play a critical role in cancer biology and are frequently aberrantly expressed. Despite their important role in pathology, little is known mechanistically regarding their role in gastric cancer (GC) pathogenesis. To characterize the role of lncRNAs in GC pathogenesis, 8 paired human GC tissue samples and matched adjacent normal tissue were examined. Large scale expression profiling of lncRNA and mRNA was performed utilizing microarray technology and validated by qPCR. Differentially expressed lncRNAs were subjected to bioinformatic analysis to predict target genes, followed by the integration of differentially expressed mRNA data and GO and network analysis to further characterize potential interactions. In our study, 2,621 lncRNAs and 3,121 mRNAs were identi?ed to be differentially expressed (?2.0-fold change) in GC samples relative to their matched counterparts. lncRNA target prediction revealed the presence of 221 potential lncRNA-mRNA target pairs for the 75 differentially expressed lncRNAs and 60 differentially expressed genes. KEGG pathway analysis showed that these target genes were significantly enriched in 7 different pathways, of which the p53 signaling pathway was the most signi?cant and has been previously implicated in GC pathogenesis. Construction of a lncRNA-mRNA correlation network revealed 10 differentially expressed lncRNAs potentially regulating the p53 signaling pathway. Overall, this is the first study perform global expression profiling of lncRNAs and mRNAs relating to GC. These results may provide important information for further insights into the pathogenesis of GC and provide potential targets for future therapeutics.
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Graft-versus-host disease causes broad suppression of hematopoietic primitive cells and blocks megakaryocyte differentiation in a murine model.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-06-2014
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Cytopenia and delayed immune reconstitution with acute graft-versus-host disease (aGVHD) indicate a poor prognosis. However, how donor-derived cell hematopoiesis is impaired in aGVHD is not well understood. We addressed this issue by studying the kinetics of hematopoiesis and the functions of hematopoietic stem and progenitor cells in an aGVHD model with haplo-MHC-matched murine bone marrow transplantation. Although hematopoiesis was progressively suppressed during aGVHD, the hematopoietic regenerative potential of donor-derived hematopoietic stem cells remains intact. There was a dramatic reduction in primitive hematopoietic cells and a defect in the ability of these cells to generate common myeloid progenitors (CMPs) and megakaryocyte/erythrocyte progenitors (MEPs). These effects were observed along with a concomitant increase in granulocyte/macrophage progenitors, suggesting that differentiation into MEPs is blocked during aGVHD. Interestingly, cyclosporine A was able to partially reverse the hematopoietic suppression as well as the differentiation blockage of CMPs. These data provide new insights into the pathogenesis of aGVHD and may improve the clinical management of aGVHD.
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Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty.
Nutrition
PUBLISHED: 01-12-2014
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The onset of puberty in females has been occurring earlier over the past decades, presumably as a result of improved nutrition in developed countries. However, the underlying molecular mechanisms responsible for the early attainment of puberty as a result of nutrition fortification remain largely unknown. The aim of this study was to evaluate the hormone and gene expression changes in prepubescent gilts fed a high-fat diet to investigate whether these changes could predict the early timing of puberty.
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Magnetization Transfer Prepared Gradient Echo MRI for CEST Imaging.
PLoS ONE
PUBLISHED: 01-01-2014
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Chemical exchange saturation transfer (CEST) is an emerging MRI contrast mechanism that is capable of noninvasively imaging dilute CEST agents and local properties such as pH and temperature, augmenting the routine MRI methods. However, the routine CEST MRI includes a long RF saturation pulse followed by fast image readout, which is associated with high specific absorption rate and limited spatial resolution. In addition, echo planar imaging (EPI)-based fast image readout is prone to image distortion, particularly severe at high field. To address these limitations, we evaluated magnetization transfer (MT) prepared gradient echo (GRE) MRI for CEST imaging. We proved the feasibility using numerical simulations and experiments in vitro and in vivo. Then we optimized the sequence by serially evaluating the effects of the number of saturation steps, MT saturation power (B1), GRE readout flip angle (FA), and repetition time (TR) upon the CEST MRI, and further demonstrated the endogenous amide proton CEST imaging in rats brains (n?=?5) that underwent permanent middle cerebral artery occlusion. The CEST images can identify ischemic lesions in the first 3 hours after occlusion. In summary, our study demonstrated that the readily available MT-prepared GRE MRI, if optimized, is CEST-sensitive and remains promising for translational CEST imaging.
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Maternal protein restriction alters VEGF signaling and decreases pulmonary alveolar in fetal rats.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Epidemiological studies have demonstrated that intrauterine growth restriction (IUGR) increases the risk for respiratory morbidity from infancy, throughout childhood and into adulthood. Chronic restriction of nutrients causes abnormalities in the airways and lungs of offspring, but whether IUGR adversely impacts fetal pulmonary vascular development and underlying mechanisms remain under investigation. In this study, we investigated the effects of protein malnutrition in utero on pulmonary alveolarization and vascular growth of the fetal lung and placentae. Pregnant rats were feed with an isocaloric low-protein diet (8% protein) until delivery. Placenta and fetal lungs were harvested on 20th day of gestation (term 21 days of gestation). Lung index (lung weight as a percentage of body weight), total DNA and protein, radial alveolar count, arteriolar wall thickness, lung maturity and angiogenic factor VEGF were assessed. The lung was hypoplastic in IUGR fetus, evidenced by reduction in lung weight, DNA and protein content. Protein restriction in utero led to higher glycogen levels, but reduced number of alveoli as confirmed by the measurement of radial alveolar counts. IUGR fetus had significantly reduced VEGF, Flk-1 levels in lung but no changes in Flt-1 mRNA. Furthermore, IUGR was associated with increased lung miR-126-3p levels, which modulated the expression of angiogenic factor. In contrast, with regard to the placenta, IUGR fetus presented with decreased expression of VEGF, with no changes in VEGF receptors and expression-regulating miRNAs. This work suggested that VEGF signaling defect plays an important role in the defective lung development, which may explain the increased incidence of respiratory infections in IUGR patients.
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Multiple idiopathic cervical root resorptions: report of one case with 8 teeth involved successively.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Multiple idiopathic cervical root resorptions is a rare condition which is usually detected as an incidental radiographic finding. It involves more than 3 teeth in the same patient and the etiology remains elusive. Diagnosis and treatment of the defect is still challenging. The present report describes a case with progressive multiple external cervical resorption involving 8 teeth, including the history, clinical and radiographic findings. Treatment included surgical intervention and restoration of the defect. A 3-month reevaluation of the case confirmed a stable, uneventful clinical recovery.
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Use of sodium butyrate as an alternative to dietary fiber: effects on the embryonic development and anti-oxidative capacity of rats.
PLoS ONE
PUBLISHED: 01-01-2014
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In this study, we evaluated the effect of replacing dietary fiber with sodium butyrate on reproductive performance and antioxidant defense in a high fat diet during pregnancy by using a rat model. Eighty virgin female Sprague Dawley rats were fed one of four diets--(1) control diet (C group), (2) high fat + high fiber diet (HF group), (3) high-fat +5% sodium butyrate diet (SB group), and (4) HF diet + ?-cyano-4-hydroxy cinnamic acid (CHC group)--intraperitoneally on days 8, 10, 12, 14, and 16 of gestation. SB and dietary fiber had similar effects on improving fetal number and reducing the abortion rate; however, the anti-oxidant capacity of maternal serum, placenta, and fetus was superior in the HF group than in the SB group. In comparison, CHC injection decreased reproductive performance and antioxidant defense. Both dietary fiber (DF) and SB supplementation had a major but different effect on the expression of anti-oxidant related genes and nutrient transporters genes. In summary, our data indicate that SB and DF showed similar effect on reproductive performance, but SB cannot completely replace the DF towards with respect to redox regulation in high-fat diet; and SB might influence offspring metabolism and health differently to DF.
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Is resistance to anti-tuberculosis drugs associated with type 2 diabetes mellitus? A register review in Beijing, China.
Glob Health Action
PUBLISHED: 01-01-2014
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China has a high burden of drug-resistant tuberculosis (TB) and diabetes mellitus (DM).
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Expression and function of kisspeptin during mouse decidualization.
PLoS ONE
PUBLISHED: 01-01-2014
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Plasma kisspeptin levels dramatically increased during the first trimester of human pregnancy, which is similar to pregnancy specific glycoprotein-human chorionic gonadotropin. However, its particular role in the implantation and decidualization has not been fully unraveled. Here, the study was conducted to investigate the expression and function of kisspeptin in mouse uterus during early pregnancy and decidualization.
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Urotensin II promotes atherosclerosis in cholesterol-fed rabbits.
PLoS ONE
PUBLISHED: 01-01-2014
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Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P?=?0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P?=?0.005), 11% in the thoracic aorta (P?=?0.054) and 18% in the abdominal aorta (P?=?0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.
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Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF) and Alzheimer's disease (AD) has been widely reported, but the results remain controversial.
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Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii.
Amino Acids
PUBLISHED: 01-01-2014
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Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 ?M against Gram-negative Escherichia coli, 4.3 ?M against Gram-positive Staphylococcus aureus and 4-9 ?M against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6%) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.
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TGF-? promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways.
Biochem. Biophys. Res. Commun.
PUBLISHED: 12-11-2013
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While there were certain studies focusing on the mechanism of TGF-? promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-? may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-? was added, whereas the TGF-?-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-?-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-? addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-? weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-? more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-? and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.
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Comprehensive analysis on clinical features of Wilsons disease: an experience over 28 years with 133 cases.
Neurol. Res.
PUBLISHED: 12-06-2013
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Here, we reported our experience over 28 years with 133 cases of patients with Wilsons disease (WD) in order to illustrate the diverse clinical presentation and to improve understanding and early diagnosis of WD.
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The role of collagen charge clusters in the modulation of matrix metalloproteinase activity.
J. Biol. Chem.
PUBLISHED: 12-02-2013
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Members of the matrix metalloproteinase (MMP) family selectively cleave collagens in vivo. Several substrate structural features that direct MMP collagenolysis have been identified. The present study has evaluated the role of charged residue clusters on the regulation of MMP collagenolysis. A series of 10 triple-helical peptide (THP) substrates were constructed in which either Lys-Gly-Asp or Gly-Asp-Lys motifs replaced Gly-Pro-Hyp repeats. The stabilities of THPs containing the two different motifs were analyzed, and kinetic parameters for substrate hydrolysis by 6 MMPs determined. A general trend for virtually all enzymes was that, as Gly-Asp-Lys motifs were moved from the extreme N- and C-termini to the interior next to the cleavage site sequence, kcat/KM values increased. Additionally, all Gly-Asp-Lys THPs were as good or better substrates than the parent THP, in which Gly-Asp-Lys was not present. In turn, the Lys-Gly-Asp THPs were also always better substrates than the parent THP, but the magnitude of the difference was considerably less compared with the Gly-Asp-Lys series. Of the MMPs tested, MMP-2 and MMP-9 most greatly favored the presence of charged residues, with preference for the Gly-Asp-Lys series. Lys-Gly-[Asp/Glu] motifs are more commonly found near potential MMP cleavage sites then Gly-[Asp/Glu]-Lys motifs. As Lys-Gly-Asp is not as favored by MMPs as Gly-Asp-Lys, the Lys-Gly-Asp motif appears advantageous over the Gly-Asp-Lys motif by preventing unwanted MMP hydrolysis. More specifically, the lack of Gly-Asp-Lys clusters may diminish potential MMP-2 and MMP-9 collagenolytic activity. The present study indicates that MMPs have interactions spanning the P23-P23 subsites of collagenous substrates.
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[Chemical constituents of Paederia pertomentosa].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 11-16-2013
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Five constituents were extracted from the aerial part of Paederia pertomentosa and isolated by column chromatography. Their structures were elucidated by physicochemical properties and spectroscopic data analysis. The isolated compounds were identified as 1,2-dimethoxy-3,4-dihydroxyanthraquinone named as paederone (1), paederoside (2), deacetyl asperulosidic acid methyl ester (3), paederosidic acid (4) and methylpaederosidate (5). Compound 1 is a new compound which exhibits a significant inhibitory effect on Escherichia coli and Staphylococcus aureus. Compounds 2-5 were isolated from this plant for the first time.
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DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements.
Nucleic Acids Res.
PUBLISHED: 11-15-2013
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The combination of high-density transposon-mediated mutagenesis and high-throughput sequencing has led to significant advancements in research on essential genes, resulting in a dramatic increase in the number of identified prokaryotic essential genes under diverse conditions and a revised essential-gene concept that includes all essential genomic elements, rather than focusing on protein-coding genes only. DEG 10, a new release of the Database of Essential Genes (available at http://www.essentialgene.org), has been developed to accommodate these quantitative and qualitative advancements. In addition to increasing the number of bacterial and archaeal essential genes determined by genome-wide gene essentiality screens, DEG 10 also harbors essential noncoding RNAs, promoters, regulatory sequences and replication origins. These essential genomic elements are determined not only in vitro, but also in vivo, under diverse conditions including those for survival, pathogenesis and antibiotic resistance. We have developed customizable BLAST tools that allow users to perform species- and experiment-specific BLAST searches for a single gene, a list of genes, annotated or unannotated genomes. Therefore, DEG 10 includes essential genomic elements under different conditions in three domains of life, with customizable BLAST tools.
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Polybromobenzene pollutants in the atmosphere of North China: levels, distribution, and sources.
Environ. Sci. Technol.
PUBLISHED: 11-01-2013
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Brominated flame retardants (BFRs) are important persistent organic pollutants. Analysis of BFRs in atmospheric samples in a previous study led us to suspect the presence of unidentified organic bromides, other than polybrominated diphenyl ethers (PBDEs), in the atmosphere. In this study, we identified and quantified polybromobenzenes, a group of organic bromides, in air samples collected through passive sampling in gridded observations in North China. We investigated their concentrations and spatial distribution, and estimated the proportion due to different sources. We detected seven species of polybromobenzenes, including hexabromobenzene (HBB), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB), pentabromobenzene (PeBB), tetrabromobenzenes (TeBBs), and tribromotoluene (TrBT), in all or most of the field samples, indicating widespread occurrence of this class of pollutants. The median concentrations of each pollutant ranged from 20.0 to 144 pg/sample (or from 0.07 to 1.16 pg/m(3)), with relatively high concentrations found near e-waste recycling sites, BFR manufacturing sites, and areas of high population density. Positive matrix factorization (PMF) analysis revealed that ?70% of HBB, PBT, PBEB, and PeBB was from commercial products, while ?80% of 1,2,3,5-TeBB, 1,2,4,5-TeBB, and 2,4,5-TrBT was linked with BFR manufacturing. This study provides essential information on widespread polybromobenzene pollutants in the atmosphere, particularly TeBBs and TrBT, for which this is the first report of their presence as atmospheric pollutants.
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Association of inorganic arsenic exposure with type 2 diabetes mellitus: a meta-analysis.
J Epidemiol Community Health
PUBLISHED: 10-16-2013
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The association of long-term effects of inorganic arsenic (iAs) exposure with type 2 diabetes mellitus (T2DM) risk remains controversial.
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Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 10-01-2013
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Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.
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Diabetes mellitus and tuberculosis: pattern of tuberculosis, two-month smear conversion and treatment outcomes in Guangzhou, China.
Trop. Med. Int. Health
PUBLISHED: 09-23-2013
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There is a high burden of both diabetes (DM) and tuberculosis (TB) in China. We evaluated the association between DM and the pattern of disease, 2-month sputum smear conversion and treatment outcomes of patients with TB in Guangzhou, China.
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Gridded Field Observations of Polybrominated Diphenyl Ethers in Soils of North China.
Arch. Environ. Contam. Toxicol.
PUBLISHED: 09-19-2013
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Polybrominated diphenyl ethers (PBDEs) were measured in 87 soil samples collected from North China. Eleven PBDE congeners (BDE28, 47, 49, 66, 99, 100, 119, 183, 196, 203, and 209) were identified with a high frequency of detection (84-100 %) in soil samples, and their frequencies were used for statistical analysis in the present study. PBDE concentrations ranged from 0.08 to 8260 ng/g with a mean of 202 ng/g, thus indicating severe pollution at these sample sites. BDE209 was the predominant congener with concentrations of 0.08-8140 ng/g (mean 188). Analysis of the spatial distribution of PBDEs in North China soils indicated that relatively high concentrations of both lower- and higher-brominated BDEs were present in Shandong Province, and a decreasing trend in PBDE concentrations from the east toward the west of North China was observed. Source identification analysis suggested that Jinghai County in Tianjin and the coastal area of Laizhou Bay, Shandong province, were the major sources in North China. The sources in Jinghai County were connected with the dismantling of electronic waste, whereas the sources in the coastal area of Laizhou Bay were connected with the production of PBDEs. Modeling results showed that the distance between the sampling sites and these point sources had a large influence on the transfer of PBDEs.
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[Effects of zhuhong ointment on MMPs activities and production by HSF].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-10-2013
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HuaFu Shengji is the primary traditional Chinese medicine (TCM) therapy for treating chronic skin ulcer. The high activities of the protein enzyme in the wound fluids is one of the main cause of healing delay. In order to investigate the effect of TCM Zhuhong ointment for promoting wound healing. This research focused on its influence on matrix metalloproteinase (MMP) activities in wound fluids with TCM Yang syndromes, directly on the activated MMP-1,2 activities in vitro and on MMP-1,-2,-9 production by HSF. 8 wound fluid samples were collected, which were diagnosed Yang Syndromes in TCM. Wound fluid activities of MMP-2 and MMP-9 were measured by gelatin zymogram assay. MMP-1 and MMP-2 activities in vitro were measured by substrate cleavage. CCK-8 was used to observe the toxicity of Zhuhong ointment on HSF. MMP-1,-2,-9 production by HSF were detected by confocal microscope. Zhuhong ointment from 1 to 25 g x L(-1) obviously inhibited MMP-2 activity in wound fluid. When Zhuhong ointment was over 5 g x L(-1), it showed significantly inhibitory effect on wound fluid MMP-9 activity. In vitro study, when the mercury concentration was 320 mg x L(-1), Zhuhong ointment solution directly inhibited both MMP-1 activity and MMP-2. But mercury concentration from 0.51-2.56 mg x L(-1), it could activate MMP-1 activity, and from 0.51-64 mg x L(-1), activate MMP-2 activity instead. The mercury concentration when Zhuhong ointment saturated in DMEM was 39.6 mg x L(-1). When the mercury concentration was over 1.23 mg x L(-1), Zhuhong ointment showed toxicity to HSF. At 1.23, 0.62, 0.31 mg x L(-1) of mercury concentration, it increased MMP-1 expression by HSF, and at 1.23, 0.62 mg x L(-1), decreased MMP-2 expression. However, at 1.23, 0.62, 0.31 mg x L(-1), it decreased MMP-9 expression. At higher concentration, Zhuhong ointment can inhibit MMP-2, MMP-9 activities in wound fluid with dose-dependent way and show a direct inhibitory effect on activated MMP-1 and MMP-2 in vitro. But at a lower concentration, it showed two-way adjustment, with increased MMP-1, MMP-2 activities and its expression by HSF and decreased MMP-9 activity.
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Calcium carbonate does not affect nilotinib pharmacokinetics in healthy volunteers.
Cancer Chemother. Pharmacol.
PUBLISHED: 08-28-2013
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Gastric upset is a common side effect of nilotinib therapy, and calcium carbonate is frequently used concomitantly, either as antacid or as calcium supplementation. With the increasing number of oral agents in cancer therapy, oral drug-drug interactions are becoming more relevant. Nilotinib has already been shown to be absorbed to a much lesser extent when co-administered with proton pump inhibitors. Because exposure to sub-therapeutic concentrations of anticancer drugs such as nilotinib may result in selection of resistant clones and ultimately relapse, we studied the effect of a calcium carbonate supplement (Tums Ultra 1000®) on nilotinib pharmacokinetics.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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