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Agent Capable (agent + capable)
Selected AbstractsA keratinocytes,melanocytes coculture system for the evaluation of active ingredients' effects on UV-induced melanogenesisINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1-2 2003J.-F. Nicolaÿ Synopsis A new experimental design, more reliable for in vitro testing of active ingredients' effect on ultraviolet (UV)-induced melanogenesis has been carried out. It uses a bicompartmental coculture system where cell communication between keratinocytes and melanocytes can take place. Thus, this experimental situation enables to monitor the effect of biological agents released by both cell types on melanogenesis and the interference of tested compounds with this ,paracrine linkage'. Experiments with UVB-irradiated cocultures show the importance of cell communication in the melanogenic response. In this model, the endogenous mediator, nitric oxide (NO), increased melanin production. Different compounds were tested in the coculture system, and comparison with data obtained from irradiated monocultures of melanocytes enables to distinguish a specific effect on cell communication. In addition, this more close-to-reality experimental model proved to provide a valuable first approach for the assessment of the ,bioavailability' of the tested substances. Finally, the effect of an innovative photoprotective agent capable of ,boosting' UV-induced melanogenic cell communication is presented. Résumé Un nouveau concept expérimental, plus fiable pour l,évaluation in vitro de l,effet de principes actifs sur la mélanogénèse induite par les UV, a été mis en ,uvre. Il utilise un système de co-culture à double compartiment dans lequel une communication cellulaire entre les kératinocytes et les mélanocytes peut s,établir. Ainsi, ce système expérimental permet de suivre l,effet des agents biologiques libérés par les deux types de cellules sur la mélanogénèse, et les interférences des composés testés avec ce ,lien paracrine'. Les essais avec des co-cultures irradiées aux UV montrent l,importance de la communication cellulaire dans la réponse mélanogénique. Avec ce modèle, le médiateur oxyde nitrique endogène (NO) augmente la production de mélanine. Différents composés ont été testés avec ce système de co-culture, et une comparaison avec les données obtenues à partir de monocultutres de mélanocytes irradiées permet de distinguer un effet spécifique sur la communication cellulaire. En outre, ce modèle expérimental plus proche de la réalité s,est avéré apporter une première approche valable de l,évaluation de la ,biodisponibilité' des substances testées. Enfin, l,effet d,un agent protecteur innovant capable de stimuler la communication cellulaire mélanogénique induite par les UV est décrit. [source] 6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12- O -tetradecanoylphorbol 13-acetate-induced tumor promotion in miceMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2010Hou Wu Abstract We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12- O -tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-,B subunits. 6-Shogaol also reduced TPA-induced phosphorylation of I,B, and p65, and caused subsequent degradation of I,B,. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-,B and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20,wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis. [source] Testing the relationship between self-agency and enactment of health behaviorsRESEARCH IN NURSING & HEALTH, Issue 1 2003Janiece DeSocio Abstract A theoretical review provides a rationale for examining self-agency as a developmental foundation underlying processes of self-regulated change and a potential moderator of intervention effectiveness among participants in a nurse home-visitation program. Self-agency is defined as the conceptual understanding of self as an agent capable of shaping motives, behavior, and future possibilities (Damon & Hart, 1991). Availability of a sample of 186 mothers who received nurse home visitation provided an opportunity to test the relationship between participant self-agency and enactment of targeted health behaviors. Self-agency items from the Pearlin Mastery Scale (1978) were used to differentiate mothers who endorsed self-agency from those who did not. Consistent with the theoretical premise, mothers who endorsed self-agency at an established threshold were significantly more likely to enact health behaviors promoted during nurse visitation. Results provide support for the relationship between the development of self-agency and enactment of health behaviors targeted by a nurse home-visitation program. © 2003 Wiley Periodicals, Inc. Res Nurs Health 26:20,29, 2003 [source] Design of (Gd-DO3A)n -polydiamidopropanoyl-peptide nucleic acid- D(Cys-Ser-Lys-Cys) magnetic resonance contrast agentsBIOPOLYMERS, Issue 12 2008Nariman V. Amirkhanov Abstract We hypothesized that chelating Gd(III) to 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide (DO3A) on peptide nucleic acid (PNA) hybridization probes would provide a magnetic resonance genetic imaging agent capable of hybridization to a specific mRNA. Because of the low sensitivity of Gd(III) as an magnetic resonance imaging (MRI) contrast agent, a single Gd-DO3A complex per PNA hybridization agent could not provide enough contrast for detection of cancer gene mRNAs, even at thousands of mRNA copies per cell. To increase the Gd(III) shift intensity of MRI genetic imaging agents, we extended a novel DO3An -polydiamidopropanoyl (PDAPm) dendrimer, up to n = 16, from the N-terminus of KRAS PNA hybridization agents by solid phase synthesis. A C-terminal D(Cys-Ser-Lys-Cys) cyclized peptide analog of insulin-like growth factor 1 (IGF1) was included to enable receptor-mediated cellular uptake. Molecular dynamic simulation of the (Gd-DO3A-AEEA)16 -PDAP4 -AEEA2 - KRAS PNA-AEEA- D(Cys-Ser-Lys-Cys) genetic imaging nanoparticles in explicit water yielded a pair correlation function similar to that of PAMAM dendrimers, and a predicted structure in which the PDAP dendron did not sequester the PNA. Thermal melting measurements indicated that the size of the PDAP dendron included in the (DO3A-AEEA)n -PDAPm -AEEA2 - KRAS PNA-AEEA- D(Cys-Ser-Lys-Cys) probes (up to 16 Gd(III) cations per PNA) did not depress the melting temperatures (Tm) of the complementary PNA/RNA hybrid duplexes. The Gd(III) dendrimer PNA genetic imaging agents in phantom solutions displayed significantly greater T1 relaxivity per probe (r1 = 30.64 ± 2.68 mM,1 s,1 for n = 2, r1 = 153.84 ± 11.28 mM,1 s,1 for n = 8) than Gd-DTPA (r1 = 10.35 ± 0.37 mM,1 s,1), but less than that of (Gd-DO3A)32 -PAMAM dendrimer (r1 = 771.84 ± 20.48 mM,1 s,1) (P < 0.05). Higher generations of PDAP dendrimers with 32 or more Gd-DO3A residues attached to PNA- D(Cys-Ser-Lys-Cys) genetic imaging agents might provide greater contrast for more sensitive detection. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 1061,1076, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Platinum-based anticancer agents: Innovative design strategies and biological perspectivesMEDICINAL RESEARCH REVIEWS, Issue 5 2003Yee-Ping Ho Abstract The impact of cisplatin on cancer chemotherapy cannot be denied. Over the past 20 years, much effort has been dedicated to discover new platinum-based anticancer agents that are superior to cisplatin or its analogue, carboplatin. Most structural modifications are based on changing one or both of the ligand types coordinated to platinum. Altering the leaving group can influence tissue and intracellular distribution of the drug, whereas the carrier ligand usually determines the structure of adducts formed with DNA. DNA,Pt adducts produced by cisplatin and many of its classical analogues are almost identical, and would explain their similar patterns of tumor sensitivity and susceptibility to resistance. Recently some highly innovative design strategies have emerged, aimed at overcoming platinum resistance and/or to introduce novel mechanisms of antitumor action. Platinum compounds bearing the 1,2-diaminocyclohexane carrier ligand; and those of multinuclear Pt complexes giving rise to radically different DNA,Pt adducts, have resulted in novel anticancer agents capable of circumventing cisplatin resistance. Other strategies have focused on integrating biologically active ligands with platinum moieties intended to selectively localizing the anticancer properties. With the rapid advance in molecular biology, combined with innovation, it is possible new Pt-based anticancer agents will materialize in the near future. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 5, 633,655, 2003 [source] Skin symptoms and work-related skin symptoms among grape farmers in Crete, GreeceAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2006Leda Chatzi MD Abstract Background Grape farmers are exposed to a variety of agents capable of inducing occupational skin disease. We conducted a study to measure the prevalence of skin symptoms and work-related skin symptoms among grape farmers in the Malevisi region of Crete and to provide data on associated risk factors. Methods One hundred twenty grape farmers and 100 controls participated in the study. The protocol consisted of a questionnaire, skin prick tests for 16 common allergens, and measurement of specific IgE antibodies against 8 allergens. Results Self-reported itchy rash (OR, 2.31; 95%CI, 1.10,4.84, P,<,0.05) within the last 12 months, and work-related itchy rash (OR, 4.08; 95%CI, 1.01,20.33, P,<,0.05) were significantly higher in grape farmers than in controls, after adjusting for age and sex. Sensitization to pollens (OR, 4.20; 95% CI, 1.41,12.82, P,<,0.01) and allergic rhinitis (OR, 3.06; 95% CI, 1.21,8.28, P,<,0.05) were found to be significantly associated with self-reported itchy rash in the grape farmers group. Conclusions Grape farmers reported skin symptoms more frequently than non-exposed controls, and IgE-mediated sensitization to pollens was found to be significantly associated with the reported symptoms. Further studies are needed to evaluate the impact of specific occupational agents on skin diseases among grape farmers. Am. J. Ind. Med., 2006. © 2005 Wiley-Liss, Inc. [source] Development and validation of a high-performance liquid chromatography method for the simultaneous determination of aspirin and folic acid from nano-particulate systemsBIOMEDICAL CHROMATOGRAPHY, Issue 9 2010Abhishek Chaudhary Abstract Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive analytical method exists to simultaneously quantify the two drugs when released from polymer-based nanoparticles. Thus, a rapid, highly sensitive method of high-performance liquid chromatography analysis to simultaneously detect low quantities of aspirin (hydrolyzed to salicylic acid, the active moiety) and folic acid released from biodegradable polylactide-co-glycolide (PLGA) copolymer nanoparticles was developed. Analysis was done on a reversed-phase C18 column using a photodiode array detector at wavelengths of 233,nm (salicylic acid) and 277,nm (folic acid). The mobile phase consisted of acetonitrile,0.1% trifluoroacetic acid mixture programmed for a 30,min gradient elution analysis. In the range of 0.1,100,,g/mL, the assay showed good linearity for salicylic acid (R2 = 0.9996) and folic acid (R2 = 0.9998). The method demonstrated good reproducibility, intra- and inter-day precision and accuracy (99.67, 100.1%) and low values of detection (0.03, 0.01,,g/mL) and quantitation (0.1 and 0.05,,g/mL) for salicylic acid and folic acid, respectively. The suitability of the method was demonstrated by simultaneously determining salicylic acid and folic acid released from PLGA nanoparticles. Copyright © 2009 John Wiley & Sons, Ltd. [source] Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signaturesCANCER, Issue 16 2009Chiara Braconi MD Abstract BACKGROUND: The presence of vascular invasion in hepatocellular cancer (HCC) correlates with prognosis, and is a critical determinant of both the therapeutic approach and the recurrence or intrahepatic metastases. The authors sought to identify candidate therapeutic agents capable of targeting the invasive phenotype in HCC. METHODS: A gene expression signature associated with vascular invasion derived from 81 human cases of HCC was used to screen a database of 453 genomic profiles associated with 164 bioactive molecules using the connectivity map. Candidate agents were identified by their inverse correlation to the query gene signature. The efficacy of the candidate agents to target invasion was experimentally verified in PLC/PRF-5 and HepG2 HCC cells. RESULTS: The gene signature associated with vascular invasion in HCC comprised of 47 up-regulated and 26 down-regulated genes. Computational bioinformatics analysis revealed several putative candidates, including resveratrol and 17-allylamino-geldanamycin (17-AAG). Both of these agents reduced HCC cell invasion at noncytotoxic concentrations. 17-AAG, a heat shock protein 90 (HSP-90) inhibitor, was shown to modulate the expression of several diverse cancer-associated genes, including ADAMTS1, part of the query signature, and maspin, an HSP-90,associated protein with a tumor suppressor role in HCC. CONCLUSIONS: Candidates for further evaluation as therapies to limit invasion in HCC have been identified using a computational bioinformatics analysis of phenotype-associated gene expression. Phenotype targeting using genomic profiling is a rational approach for drug discovery. Therapeutic strategies targeting a defined cancer-associated phenotype can be identified without a detailed knowledge of individual downstream targets. Cancer 2009. © 2009 American Cancer Society. [source] | |||||||||||||