undergraduate research cur: Topics by Science.gov

Sample records for undergraduate research cur

Undergraduate Research as a Primary Pathway to STEM Careers: Perspectives from the Council on Undergraduate Research

NASA Astrophysics Data System (ADS)

Manley, P. L.; Ambos, E. L.

2012-12-01

Undergraduate research (UR) is one of the most authentic and effective ways to promote student learning, and is a high-impact educational practice that can lead to measurable gains in student retention and graduation rates, as well as career aspirations. In recent years, UR has expanded from intensive summer one-on-one faculty-student mentored experiences to application in a variety of educational settings, including large lower division courses. The Council on Undergraduate Research (CUR), founded in 1978, is a national organization of individual (8000) and institutional members (650) within a divisional structure that includes geosciences, as well as 10 other thematic areas. CUR's main mission is to support and promote high-quality undergraduate student-faculty collaborative research and scholarship that develops learning through research. CUR fulfills this mission through extensive publication offerings, faculty and student-directed professional development events, and outreach and advocacy activities that share successful models and strategies for establishing, institutionalizing, and sustaining undergraduate research programs. Over the last decade, CUR has worked with hundreds of academic institutions, including two-year colleges, to develop practices to build undergraduate research into campus cultures and operations. As documented in CUR publications such as Characteristics of Excellence in Undergraduate Research (COEUR), strategies institutions may adopt to enhance and sustain UR often include: (1) the establishment of a central UR campus office, (2) extensive student and faculty participation in campus-based, as well as regional UR celebration events, (3) development of a consistent practice of assessment of UR's impact on student success, and, (4) establishment of clear policies for recognizing and rewarding faculty engagement in UR, particularly with respect to mentorship and publication with student scholars. Three areas of current focus within the international UR community are particularly important to considerations of broadening and strengthening the pipeline of students entering careers in geosciences and other STEM disciplines: (1) embedding UR more effectively and systematically throughout the undergraduate curriculum, (2) connecting UR experiences with student developmental arcs in content knowledge and skill integration, and, (3) growing the scholarship of study of impact of UR on student success and professional achievements. Case studies of institutions, particularly those that represent collaborations between two and four year colleges and universities, that are successfully addressing these focus areas will be presented, along with specific challenges to expanding the use of UR in lower division curricula.
A Survey of Library Support for Formal Undergraduate Research Programs

ERIC Educational Resources Information Center

Hensley, Merinda Kaye; Shreeves, Sarah L.; Davis-Kahl, Stephanie

2014-01-01

Undergraduate research is defined by the Council on Undergraduate Research (CUR) as "an inquiry or investigation conducted by an undergraduate student that makes an original intellectual or creative contribution to the discipline." This study serves as a snapshot of current library practices in relation to formal undergraduate research…
Undergraduate Research Summer Fellowships Undergo Change

NASA Astrophysics Data System (ADS)

Elgren, Timothy E.

2000-09-01

At the 22nd Annual Council Meeting of Council on Undergraduate Research (CUR), held this past June at the College of Wooster, the general council voted to make fundamental changes to the Undergraduate Research Summer Fellowship Program. The most important change is that awards will no longer be made to individual students. Instead, awards will be made to individual faculty member on the basis of applications written by faculty members comprised of a curriculum vitae, a description of the proposed research project, and the role of undergraduate collaborators in the proposed research activities. This change brings the program more in line with the overall CUR objective to support faculty in their efforts to provide research experiences for undergraduate students. Faculty members selected for awards will be asked to designate a student recipient at the time the funds are awarded, a key change to the fellowship program.
Undergraduate Research as a Process for STEM Teaching and Learning Systemic Change: Lessons Learned from the Council on Undergraduate Research NSF CCLI and TUES Projects

NASA Astrophysics Data System (ADS)

Ambos, E. L.; Havholm, K. G.; Malachowski, M.; Osborn, J.; Karukstis, K.

2013-12-01

For more than seven years, the Council on Undergraduate Research (CUR), the primary organization supporting programs, services, and advocacy for undergraduate research, has been working with support from the NSF's Division of Undergraduate Education (DUE) to enhance, sustain, and institutionalize undergraduate research in diverse STEM disciplines and higher education settings. The Council on Undergraduate Research comprises more than 9000 individual and 670 institutional members within a divisional structure that includes geosciences, as well as 11 other thematic areas. Through its most recent grant: 'Transformational Learning through Undergraduate Research: Comprehensive Support for Faculty, Institutions, State Systems and Consortia' (NSF DUE CCLI III Award #09-20275), CUR has been collaborating with six higher education systems, each selected after a rigorous national application process in 2010 and 2011. These six systems, which collectively represent 79 individual institutions, are the Council of Public Liberal Arts Colleges (COPLAC), University of Wisconsin System (UWS), California State University System (CSU), City University of New York (CUNY), Great Lakes Colleges Association (GLCA), and Pennsylvania State System of Higher Education (PASSHE). The more than 350 participants of faculty and senior-level administrators from the six systems are engaged in shared multi-faceted and multi-year professional development experiences. Teams from each system attended customized institutes facilitated by CUR experts in 2011-2012, during which the teams developed specific action plans focused on institutionalizing undergraduate research on their campus and within their system. The systems were reconvened as a group a year after the first institute, to chart progress toward achieving their goals. Based on interviews and surveys with participants, campus teams are making substantial progress toward implementation of robust undergraduate research programs, and are making concerted efforts to affect policy, workload, tenure and promotion and resource issues, which are often core factors in any STEM education change process. Several systems are now connecting individual campus-based undergraduate research efforts more effectively, and tying undergraduate research to regional workforce and economic development programs. Many campus teams are moving their department and colleges toward curricular innovations that emphasize scaffolding undergraduate research throughout the undergraduate curriculum. An NSF EAGER/WIDER supplement to the CUR CCLI III award was received in October 2012 and expanded the scope of the project to include deeper study of the changes processes underway at each of the six systems and to tease out the factors that can either promote or retard expansion of undergraduate research as a teaching and learning paradigm. Lessons learned from one of the six systems, the University of Wisconsin, will be highlighted.
The Transformative Impact of Undergraduate Research Mentoring on Students and the Role of the Council on Undergraduate Research (CUR) in Supporting Faculty Mentors

NASA Astrophysics Data System (ADS)

Fox, L. K.; Singer, J.

2015-12-01

Undergraduate Research (UR) is broadly accepted as a high impact educational practice. Student participation in UR contributes to measurable gains in content knowledge and skills/methodology, oral and written communication skills, problem solving and critical thinking, self-confidence, autonomy, among others. First-generation college students and students from underrepresented minorities that participate in UR are more likely to remain in STEM majors, persist to graduation, and pursue graduate degrees. While engagement in the research process contributes to these outcomes, the impact of the interaction with the faculty mentor is critical. A number of studies provide evidence that it is the relationship that forms with the faculty mentor that is most valued by students and strongly contributes to their career development. Faculty mentors play an important role in student development and the relationship between mentor and student evolves from teacher to coach to colleague. Effective mentoring is not an inherent skill and is generally not taught in graduate school and generally differs from mentoring of graduate students. Each UR mentoring relationship is unique and there are many effective mentoring models and practices documented in the literature. The Council on Undergraduate Research (CUR) has a long history of supporting faculty who engage in research with undergraduates and offers resources for establishing UR programs at individual, departmental, and institutional levels. The Geosciences Division of CUR leads faculty development workshops at professional meetings and provides extensive resources to support geosciences faculty as UR mentors (http://serc.carleton.edu/NAGTWorkshops/undergraduate_research/index.html). Examples of effective mentoring strategies are highlighted, including a model developed by SUNY- Buffalo State that integrates mentoring directly into the evaluation of UR.
Faculty Development Workshops to Support Establishing and Sustaining Undergraduate Research Programs in the Earth Sciences (Invited)

NASA Astrophysics Data System (ADS)

Fox, L. K.; Guertin, L. A.

2013-12-01

The Geosciences Division of the Council of Undergraduate Research (GeoCUR, http://curgeoscience.wordpress.com/) has a long history of supporting faculty who engage in undergraduate research. The division has held faculty development workshops at national meetings of the GSA and AGU for over 15 years. These workshops serve faculty at all career stages and cover multiple aspects of the enterprise of engaging students in undergraduate research. Topics covered include: getting a job (particularly at a primarily undergraduate institution), incorporating research into classes, mentoring independent research projects and identifying sources of internal and external funding. Originally, these workshops were funded through CUR and registration income. When the administrative costs to run the workshops increased, we successfully sought funding from the NSF Course, Curriculum, and Laboratory Improvement (CCLI) program. This CCLI Type 1 special project allowed the expansion of the GSA workshops from half-day to full-day and the offering of workshops to other venues, including the annual meeting of the Association of American Geographers and sectional GSA meetings. The workshops are organized and led by GeoCUR councilors, some of whom attended workshops as graduate students or new faculty. Current and past Geoscience program officers in the NSF Division of Undergraduate Education (DUE) have presented on NSF funding opportunities. Based on participant surveys, the content of the workshops has evolved over time. Workshop content is also tailored to the particular audience; for example, AGU workshops enroll more graduate students and post-docs and thus the focus is on the job ';search' and getting started in undergraduate research. To date, this CCLI Type 1 project has supported 15 workshops and a variety of print and digital resources shared with workshop participants. This presentation will highlight the goals of this workshop proposal and also provide insights about strategies for funding professional development, impact of workshops on initiating and sustaining undergraduate research programs, and future directions of this program.
Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

PubMed Central

Zheng, Songping; Gao, Xiang; Liu, Xiaoxiao; Yu, Ting; Zheng, Tianying; Wang, Yi; You, Chao

2016-01-01

Curcumin (Cur), a natural polyphenol of Curcuma longa, has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy. PMID:27354801
Distal & Proximal Influences on Men's Intentions to Resist Condoms: Alcohol, Sexual Aggression History, Impulsivity, and Social-Cognitive Factors

PubMed Central

Davis, Kelly Cue; Danube, Cinnamon L.; Neilson, Elizabeth C.; Stappenbeck, Cynthia A.; Norris, Jeanette; George, William H.; Kajumulo, Kelly F.

2015-01-01

Recent scientific evidence demonstrates that many young men commonly resist condom use with their female sex partners and that both alcohol intoxication and a history of sexual aggression may increase the risk of condom use resistance (CUR). Using a community sample of heterosexual male non-problem drinkers with elevated sexual risk (N=311), this alcohol administration study examined the direct and indirect effects of intoxication and sexual aggression history on men's CUR intentions through a sexual risk analogue. State impulsivity, CUR-related attitudes, and CUR-related self-efficacy were assessed as mediators. Results demonstrated that alcohol intoxication directly increased CUR intentions, and sexual aggression history both directly and indirectly increased CUR intentions. These findings highlight the importance of addressing both alcohol use and sexual aggression in risky sex prevention programs, as well as indicate the continued worth of research regarding the intersection of men's alcohol use, sexual aggression, and sexual risk behaviors, especially CUR. PMID:26156881
Germplasm Release: Tissue Culture-Derived Curly Top-Resistant Genetic Stock

USDA-ARS?s Scientific Manuscript database

The USDA-ARS sugarbeet research program at Kimberly is focused on discovering novel genes for resistance to beet curly top and other economically important diseases. It is vital in genetics research to develop uniform breeding lines and genetic stocks to study inheritance, gene transfer (through co...
Incorporating Genomics and Bioinformatics across the Life Sciences Curriculum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ditty, Jayna L.; Kvaal, Christopher A.; Goodner, Brad

Undergraduate life sciences education needs an overhaul, as clearly described in the National Research Council of the National Academies publication BIO 2010: Transforming Undergraduate Education for Future Research Biologists. Among BIO 2010's top recommendations is the need to involve students in working with real data and tools that reflect the nature of life sciences research in the 21st century. Education research studies support the importance of utilizing primary literature, designing and implementing experiments, and analyzing results in the context of a bona fide scientific question in cultivating the analytical skills necessary to become a scientist. Incorporating these basic scientific methodologiesmore » in undergraduate education leads to increased undergraduate and post-graduate retention in the sciences. Toward this end, many undergraduate teaching organizations offer training and suggestions for faculty to update and improve their teaching approaches to help students learn as scientists, through design and discovery (e.g., Council of Undergraduate Research [www.cur.org] and Project Kaleidoscope [www.pkal.org]). With the advent of genome sequencing and bioinformatics, many scientists now formulate biological questions and interpret research results in the context of genomic information. Just as the use of bioinformatic tools and databases changed the way scientists investigate problems, it must change how scientists teach to create new opportunities for students to gain experiences reflecting the influence of genomics, proteomics, and bioinformatics on modern life sciences research. Educators have responded by incorporating bioinformatics into diverse life science curricula. While these published exercises in, and guidelines for, bioinformatics curricula are helpful and inspirational, faculty new to the area of bioinformatics inevitably need training in the theoretical underpinnings of the algorithms. Moreover, effectively integrating bioinformatics into courses or independent research projects requires infrastructure for organizing and assessing student work. Here, we present a new platform for faculty to keep current with the rapidly changing field of bioinformatics, the Integrated Microbial Genomes Annotation Collaboration Toolkit (IMG-ACT). It was developed by instructors from both research-intensive and predominately undergraduate institutions in collaboration with the Department of Energy-Joint Genome Institute (DOE-JGI) as a means to innovate and update undergraduate education and faculty development. The IMG-ACT program provides a cadre of tools, including access to a clearinghouse of genome sequences, bioinformatics databases, data storage, instructor course management, and student notebooks for organizing the results of their bioinformatic investigations. In the process, IMG-ACT makes it feasible to provide undergraduate research opportunities to a greater number and diversity of students, in contrast to the traditional mentor-to-student apprenticeship model for undergraduate research, which can be too expensive and time-consuming to provide for every undergraduate. The IMG-ACT serves as the hub for the network of faculty and students that use the system for microbial genome analysis. Open access of the IMG-ACT infrastructure to participating schools ensures that all types of higher education institutions can utilize it. With the infrastructure in place, faculty can focus their efforts on the pedagogy of bioinformatics, involvement of students in research, and use of this tool for their own research agenda. What the original faculty members of the IMG-ACT development team present here is an overview of how the IMG-ACT program has affected our development in terms of teaching and research with the hopes that it will inspire more faculty to get involved.« less
[Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design].

PubMed

Li, Qiu-Ping; Dai, Jun-Dong; Zhai, Wen-Wen; Jiang, Qiao-Li

2014-10-01

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.
Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

PubMed

Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

2016-01-01

Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.
One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.

PubMed

Peng, Jianqing; Fumoto, Shintaro; Miyamoto, Hirotaka; Chen, Yi; Kuroda, Naotaka; Nishida, Koyo

2017-09-01

A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO 3 ) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO 3 was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO 3 nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.
Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement.

PubMed

Li, Xin; Yuan, Huiling; Zhang, Caiyun; Chen, Weidong; Cheng, Weiye; Chen, Xin; Ye, Xi

2016-08-01

We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur. Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated. Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution. The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application. © 2016 Royal Pharmaceutical Society.
Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells.

PubMed

Punfa, Wanisa; Yodkeeree, Supachai; Pitchakarn, Pornsiri; Ampasavate, Chadarat; Limtrakul, Pornngarm

2012-06-01

To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 μg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 μg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.
Molecular inclusion complex of curcumin-β-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel.

PubMed

Rachmawati, Heni; Edityaningrum, Citra Ariani; Mauludin, Rachmat

2013-12-01

Curcumin (CUR) has various pharmacological effects, but its extensive first-pass metabolism and short elimination half-life limit its bioavailability. Therefore, transdermal application has become a potential alternative to delivery CUR. To increase CUR solubility for the development of a transparent homogenous gel and also enhance the permeation rate of CUR into the skin, β-cyclodextrin-curcumin nanoparticle complex (BCD-CUR-N) was developed. CUR encapsulation efficiency was increased by raising the percentage of CUR to BCD up to 20%. The mean particle size of the best CUR loading formula was 156 nm. All evaluation data using infrared spectroscopy, Raman spectroscopy, powder X-ray diffractometry, differential thermal analysis and scanning electron microscopy confirmed the successful formation of the inclusion complex. BCD-CUR-N increased the CUR dissolution rate of 10-fold (p < 0.01). In addition, the improvement of CUR permeability acrossed skin model tissue was observed in gel containing the BCD-CUR-N and was about 1.8-fold when compared with the free CUR gel (p < 0.01). Overall, CUR in the form of the BCD-CUR-N improved the solubility further on the penetration of CUR.
Viewing Molecular and Interface Interactions of Curcumin Amorphous Solid Dispersions for Comprehending Dissolution Mechanisms.

PubMed

Li, Jing; Wang, Xin; Li, Chang; Fan, Na; Wang, Jian; He, Zhonggui; Sun, Jin

2017-08-07

Tautomeric curcumin amorphous solid dispersions (Cur ASDs) formulated with various typical polymers (polyethylene glycol 6000 (PEG), polyvinylpyrrolidone K30 (PVP), Eudragit EPO (EuD), EuD/hydroxypropylmethyl cellulose E50 (HPMC), and PVP/EuD) were probed using in situ Raman imaging plus spectroscopy and molecular modeling techniques, and dissolution mechanism of Cur ASDs were revealed mainly through molecular and interfacial interactions formed between Cur and polymer. The results demonstrated that Cur of keto form existed in Cur-PEG, Cur of enol form was shown in Cur-PVP, while Cur-EuD or Cur ASDs formulated with EuD as component had Cur of keto form and enol form. Hydrogen bond interactions were formed between OH group (PEG, HPMC) with C═O (Cur), and C═O (PVP or EuD) with the OH group (Cur). For Cur ASDs formulated with single polymer, the existed form of Cur was possibly related with the molecular interactions formed between drug and polymer. The wetting effect of excipient and Cur ASDs as well as their fitting equations of contact angle profiles should be seriously considered when analyzing the dissolution mechanism of Cur ASDs. Furthermore, dissolution of Cur-EuD with erosion dissolution pattern was higher than Cur-PVP with diffusion mechanism, and their crystallization pathway can ascribe to solution pathway and solid matrix pathway, respectively. Last but not least, turbidimetry method was effective in determining which excipient was superior and evaluating the function of polymers, including their abilities to improve amorphous Cur loading, drug dissolution, and supersaturation levels. Therefore, both the probing of tautomeric Cur in ASDs at intermolecular level and elucidation of its dissolution mechanism has tremendous value.
Hybridization of polyvinylpyrrolidone to a binary composite of curcumin/α-glucosyl stevia improves both oral absorption and photochemical stability of curcumin.

PubMed

Kadota, Kazunori; Okamoto, Daiki; Sato, Hideyuki; Onoue, Satomi; Otsu, Shigeyuki; Tozuka, Yuichi

2016-12-15

The tri-component system curcumin/α-glucosyl stevia (Stevia-G)/polyvinylpyrrolidone (PVP) was developed to improve the oral bioavailability and physicochemical properties of curcumin (CUR). The tri-component CUR formulation with Stevia-G and PVP was prepared with freeze-drying. The tri-component CUR system exhibited 13,000-fold higher solubility of CUR than the equilibrium solubility of CUR for 24h, indicating a stable tri-composite structure involving CUR. CUR could be converted into an amorphous form in the presence of Stevia-G and PVP by freeze-drying. The photo-degradation of CUR in the tri-component system was negligible even under an amorphous state of CUR. After oral administration in rats, the oral absorption of the tri-component CUR formulation (20mgCUR/kg) was 6.7-fold higher than that of crystalline CUR. The tri-component CUR formulation would therefore be a promising option to improve physicochemical properties and oral absorption of CUR. Copyright © 2016 Elsevier Ltd. All rights reserved.
Improved bioavailability and antiasthmatic efficacy of poorly soluble curcumin-solid dispersion granules obtained using fluid bed granulation.

PubMed

Jang, Dong-Jin; Kim, Sung Tae; Lee, Kooyeon; Oh, Euichaul

2014-01-01

The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin-13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR.
Influence of clay minerals on curcumin properties: Stability and singlet oxygen generation

NASA Astrophysics Data System (ADS)

Gonçalves, Joyce L. S.; Valandro, Silvano R.; Poli, Alessandra L.; Schmitt, Carla C.

2017-09-01

Curcumin (CUR) has showed promising photophysical properties regarding to biological and chemical sciences. However, the main barrier for those applications are their low solubility and stability in aqueous solution. The effects of two different clay minerals, the montmorillonite (SWy-2) and the Laponite RD (Lap) nanoclay, on the stabilization of Curcumin were investigated. Their effects were compared with two well-established environments (acidic and neutral aqueous media). CUR/clay hybrids were prepared using a simple and fast method, where CUR solution was added into clay suspensions, to obtain well dispersed hybrids in water. The degradation process of CUR and CUR/clays hybrids was investigated using UV-Vis spectroscopic. For both studied hybrids, the CUR degradation process was suppressed by the presence of the clay particles. Furthermore, the Lap showed a great stabilization effect than SWy-2. This behavior was due to the smaller particle size and higher exfoliation ability of Lap, providing a large surface for CUR adsorption compared to SWy-2. The degradation process of CUR solutions and CUR/clay hybrids was also studied in the presence of light. CUR photodegradation process was faster not only in the aqueous solution but also in the clay suspension compared to those studied in the dark. The presence of clay particles accelerated the photodegradation of CUR due to the products formation in the reactions between CUR and oxygen radicals. Our results showed that the singlet oxygen quantum yield (ΦΔ) of CUR were about 59% higher in the clay suspensions than CUR in aqueous solution. Therefore, the formation of CUR/clay hybrids, in particularly with Lap, suppressed the degradation in absence light of CUR and increased the singlet oxygen generation, which makes this hybrids of CUR/clay a promising material to enlarge the application of CUR in the biological sciences.

High drug payload curcumin nanosuspensions stabilized by mPEG-DSPE and SPC: in vitro and in vivo evaluation.

PubMed

Hong, Jingyi; Liu, Yingying; Xiao, Yao; Yang, Xiaofeng; Su, Wenjing; Zhang, Mingzhu; Liao, Yonghong; Kuang, Haixue; Wang, Xiangtao

2017-11-01

Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability. This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy. Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer. CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of -19.00 ± 1.31 mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC 0-24 and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p < 0.01). These results suggest that CUR-NSps might represent a promising drug formulation for intravenous administration of CUR for the treatment of cancer.
Medical Surveillance Monthly Report (MSMR). Volume 4, Number 4, May/June 1998

DTIC Science & Technology

1998-06-01

Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 04 / No. 04 7...transmitted diseases, US Army medical treatment facilities* May, 1998 Reporting Chlamydia Urethritis non-spec. Gonorrhea Herpes Simplex Syphilis Prim/Sec... Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Month 1998 Month 1998 Month 1998
Medical Surveillance Monthly Report (MSMR). Volume 3, Number 6, September 1997

DTIC Science & Technology

1997-09-01

1997 Prepared by the Medical Surveillance Activity, Directorate of Epidemiology and Disease Surveillance, United States Army Center for Health...Gonorrhea Herpes Simplex Syphilis Prim/Sec Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur...clinics. Not all sites reporting. Date of Report: 7-Sep-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis
Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

PubMed Central

Jiang, Shan; Zhu, Rongrong; He, Xiaolie; Wang, Jiao; Wang, Mei; Qian, Yechang; Wang, Shilong

2017-01-01

Curcumin (Cur) is a promising photosensitizer that could be used in photodynamic therapy. However, its poor solubility and hydrolytic instability limit its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) in order to improve its therapeutic activity. The Cur-loaded SLNs (Cur-SLNs) were prepared using an emulsification and low-temperature solidification method. The functions of Cur and Cur-SLNs were studied on the non-small cell lung cancer A549 cells for photodynamic therapy. The results revealed that Cur-SLNs induced ~2.27-fold toxicity higher than free Cur at a low concentration of 15 μM under light excitation, stocking more cell cycle at G2/M phase. Cur-SLNs could act as an efficient drug delivery system to increase the intracellular concentration of Cur and its accumulation in mitochondria; meanwhile, the hydrolytic stability of free Cur could be improved. Furthermore, Cur-SLNs exposed to 430 nm light could produce more reactive oxygen species to induce the disruption of mitochondrial membrane potential. Western blot analysis revealed that Cur-SLNs increased the expression of caspase-3, caspase-9 proteins and promoted the ratio of Bax/Bcl-2. Overall, the results from these studies demonstrated that the SLNs could enhance the phototoxic effects of Cur. PMID:28053531
Preparation of Curcumin-Piperazine Coamorphous Phase and Fluorescence Spectroscopic and Density Functional Theory Simulation Studies on the Interaction with Bovine Serum Albumin.

PubMed

Pang, Wenzhe; Lv, Jie; Du, Shuang; Wang, Jiaojiao; Wang, Jing; Zeng, Yanli

2017-09-05

In the present study, a new coamorphous phase (CAP) of bioactive herbal ingredient curcumin (CUR) with high solubilitythe was screened with pharmaceutically acceptable coformers. Besides, to provide basic information for the best practice of physiological and pharmaceutical preparations of CUR-based CAP, the interaction between CUR-based CAP and bovine serum albumin (BSA) was studied at the molecular level in this paper. CAP of CUR and piperazine with molar ratio of 1:2 was prepared by EtOH-assisted grinding. The as-prepared CAP was characterized by powder X-ray diffraction, modulated temperature differential scanning calorimetry, thermogravimetric analysis, Fourier-transform infrared, and solid-state 13 C nuclear magnetic resonance. The 1:2 CAP stoichioimetry was sustained by C═O···H hydrogen bonds between the N-H group of the piperazine and the C═O group of CUR; piperazine stabilized the diketo structure of CUR in CAP. The dissolution rate of CUR-piperazine CAP in 30% ethanol-water was faster than that of CUR; the t 50 values were 243.1 min for CUR and 4.378 min for CAP. Furthermore, interactions of CUR and CUR-piperazine CAP with BSA were investigated by fluorescence spectroscopy and density functional theory (DFT) calculation. The binding constants (K b ) of CUR and CUR-piperazine CAP with BSA were 10.0 and 9.1 × 10 3 L mol -1 at 298 K, respectively. Moreover, DFT simulation indicated that the interaction energy values of hydrogen-bonded interaction in the tryptophan-CUR and tryptophan-CUR-piperazine complex were -26.1 and -17.9 kJ mol -1 , respectively. In a conclusion, after formation of CUR-piperazine CAP, the interaction forces between CUR and BSA became weaker.
Medical Surveillance Monthly Report (MSMR). Volume 3, Number 4, June 1997

DTIC Science & Technology

1997-06-01

STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 03...Simplex Syphilis Prim/Sec Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Month 1997...97 Chlamydia Gonorrhea Syphilis Jun-95 Sep-95 Dec-95 Mar-96 Jun-96 Sep-96 Dec-96 Mar-97 * Reports are included from main and satellite clinics. Not
Complete genome sequences of curli-negative and curli-positive isolates of foodborne Escherichia coli O157:H7 strain 86-24

USDA-ARS?s Scientific Manuscript database

Escherichia coli O157:H7 strain 86-24 does not produce curli fimbriae, but can give rise to curli-positive isolates at a variable frequency. Here, we report the whole-genome sequences of curli-negative and curli-positive isolates of strain 86-24....
Complete Genome Sequences of Curli-Negative and Curli-Positive Isolates of Foodborne Escherichia coli O157:H7 Strain 86-24

PubMed Central

Bayles, Darrell O.; Alt, David P.; Looft, Torey

2016-01-01

Escherichia coli O157:H7 strain 86-24 does not produce curli fimbriae, but gives rise to curli-positive isolates at a variable frequency. Here, we report the complete genome sequences of curli-negative and curli-positive isolates of strain 86-24. PMID:27979932
Comparison of the colloidal stability, bioaccessibility and antioxidant activity of corn protein hydrolysate and sodium caseinate stabilized curcumin nanoparticles.

PubMed

Wang, Yong-Hui; Yuan, Yang; Yang, Xiao-Quan; Wang, Jin-Mei; Guo, Jian; Lin, Yuan

2016-07-01

The aims of this work were to construct corn protein hydrolysate (CPH)-based curcumin nanoparticles (Cur NPs) and to compare the colloidal stability, bioaccessibility and antioxidant activity of the Cur NPs stabilized CPH and sodium caseinate (NaCas) respectively. The results indicated that Cur solubility could be considerably improved after the Cur NPs fabrication. The spectroscopy results demonstrated that the solubilization of Cur should be attributed to its complexation with CPH or NaCas. The Cur NPs exhibited good colloidal stability after 1 week's storage but showed smaller (40 nm) size in CPH than in NaCas (100 nm). After lyophilization, the Cur NPs powders showed good rehydration properties and chemical stability, and compared with NaCas, the size of Cur NPs stabilized by CPH was still smaller. Additionally, the Cur NPs exhibited higher chemical stability against the temperature compared with free Cur, and the CPH could protect Cur from degradation more efficiently. Comparing with NaCas, the Cur NPs stabilized by CPH exhibited better bioaccessibility and antioxidant activity. This study demonstrated that CPH may be better than NaCas in Cur NPs fabrication and it opens up the possibility of using hydrophobic protein hydrolysate to construct the NPs delivery system.
Medical Surveillance Monthly Report (MSMR). Volume 5, Number 1, January/February 1999

DTIC Science & Technology

1999-02-01

Syphilis Latent Syphilis Tertiary Syphilis Congenital MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Month 1999 Month...group A inv. 1 0 0 0 1 Hantavirus infection 0 0 0 1 1 Syphilis , congenital 0 0 1 0 1 Heat exhaustion 6 82 118 4 210 Syphilis , latent 2 13 6 12 33...transmitted diseases, US Army medical treatment facilities* January, 1999 Reporting Chlamydia Urethritis non-spec. Gonorrhea Syphilis Prim/Sec
Complete Genome Sequences of Curli-Negative and Curli-Positive Isolates of Foodborne Escherichia coli O157:H7 Strain 86-24.

PubMed

Sharma, Vijay K; Bayles, Darrell O; Alt, David P; Looft, Torey

2016-12-15

Escherichia coli O157:H7 strain 86-24 does not produce curli fimbriae, but gives rise to curli-positive isolates at a variable frequency. Here, we report the complete genome sequences of curli-negative and curli-positive isolates of strain 86-24. Copyright © 2016 Sharma et al.
PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms.

PubMed

Xie, Xiaoxia; Tao, Qing; Zou, Yina; Zhang, Fengyi; Guo, Miao; Wang, Ying; Wang, Hui; Zhou, Qian; Yu, Shuqin

2011-09-14

The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity. Thus, encapsulating hydrophobic drugs on PLGA polymer is a promising method for sustained and controlled drug delivery with improved bioavailability of Biopharmaceutics Classification System (BCS) class IV, such as CUR.
Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

PubMed Central

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829
Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

PubMed

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.
Liposomal curcumin and its application in cancer

PubMed Central

Lee, Robert J; Zhao, Ling

2017-01-01

Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy. PMID:28860764
Liposomal curcumin and its application in cancer.

PubMed

Feng, Ting; Wei, Yumeng; Lee, Robert J; Zhao, Ling

2017-01-01

Curcumin (CUR) is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy.
A trade-off between solubility enhancement and physical stability upon simultaneous amorphization and nanonization of curcumin in comparison to amorphization alone.

PubMed

Wong, Jerome Jie Long; Yu, Hong; Lim, Li Ming; Hadinoto, Kunn

2018-03-01

The numerous health benefits of curcumin (CUR) have not been fully realized due to its low aqueous solubility, resulting in poor bioavailability. While amorphization of CUR via amorphous solid dispersion (ASD) represents a well-established CUR solubility enhancement strategy, simultaneous amorphization and nanonization of CUR via amorphous CUR nanoparticles (or nano-CUR in short) have emerged only recently as the plausibly superior alternative to ASD. Herein we examined for the first time the amorphous nano-CUR versus the ASD of CUR in terms of their (1) in vitro solubility enhancement capability and (2) long-term physical stability. The ASD of CUR was prepared by spray drying with hydroxypropylmethylcellulose (HPMC) acting as crystallization inhibitor. The amorphous nano-CUR was investigated in both its (i) aqueous suspension and (ii) dry-powder forms in which the latter was prepared by spray drying with adjuvants (i.e. HPMC, trehalose, and soy lecithin). The results showed that the amorphous nano-CUR (in both its aqueous suspension and dry-powder forms) exhibited superior solubility enhancement to the ASD of CUR attributed to its faster dissolution rates. This was despite the ASD formulation contained a larger amount of HPMC. The superior solubility enhancement, however, came at the expense of low physical stability, where the amorphous nano-CUR showed signs of transformation to crystalline after three-month accelerated storage, which was not observed with the ASD. Thus, despite its inferior solubility enhancement, the conventional ASD of CUR was found to represent the more feasible CUR solubility enhancement strategy. Copyright © 2018 Elsevier B.V. All rights reserved.
Core-shell nanofibers of curcumin/cyclodextrin inclusion complex and polylactic acid: Enhanced water solubility and slow release of curcumin.

PubMed

Aytac, Zeynep; Uyar, Tamer

2017-02-25

Core-shell nanofibers were designed via electrospinning using inclusion complex (IC) of model hydrophobic drug (curcumin, CUR) with cyclodextrin (CD) in the core and polymer (polylactic acid, PLA) in the shell (cCUR/HPβCD-IC-sPLA-NF). CD-IC of CUR and HPβCD was formed at 1:2 molar ratio. The successful formation of core-shell nanofibers was revealed by TEM and CLSM images. cCUR/HPβCD-IC-sPLA-NF released CUR slowly but much more in total than PLA-CUR-NF at pH 1 and pH 7.4 due to the restriction of CUR in the core of nanofibers and solubility improvement shown in phase solubility diagram, respectively. Improved antioxidant activity of cCUR/HPβCD-IC-sPLA-NF in methanol:water (1:1) is related with the solubility enhancement achieved in water based system. The slow reaction of cCUR/HPβCD-IC-sPLA-NF in methanol is associated with the shell inhibiting the quick release of CUR. On the other hand, cCUR/HPβCD-IC-sPLA-NF exhibited slightly higher rate of antioxidant activity than PLA-CUR-NF in methanol:water (1:1) owing to the enhanced solubility. To conclude, slow release of CUR was achieved by core-shell nanofiber structure and inclusion complexation of CUR with HPβCD provides high solubility. Briefly, electrospinning of core-shell nanofibers with CD-IC core could offer slow release of drugs as well as solubility enhancement for hydrophobic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.
Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles.

PubMed

Kheiri Manjili, Hamidreza; Ghasemi, Parisa; Malvandi, Hojjat; Mousavi, Mir Sajjad; Attari, Elahe; Danafar, Hossein

2017-07-01

Curcumin (CUR) has been associated with anti-inflammatory, antimicrobial, antioxidant, anti-amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability. To progress the bioavailability and water solubility of CUR, we synthesized five series of mono methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG-PCL) diblock copolymers. The structure of the copolymers was characterized by H NMR, FTIR, DSC and GPC techniques. In this study, CUR was encapsulated within micelles through a single-step nano-precipitation method, leading to formation of CUR-loaded mPEG-PCL (CUR/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxicity of void CUR, mPEG-PCL and CUR/mPEG-PCL micelles was compared to each other by performing MTT assay of the treated MCF-7 and 4T1 cell line. Study of the in vivo pharmacokinetics of the CUR-loaded micelles was also carried out on selected copolymers in comparison with CUR solution formulations. The results showed that the zeta potential of CUR-loaded micelles was about -11.5mV and the average size was 81.0nm. CUR was encapsulated into mPEG-PCL micelles with loading capacity of 20.65±0.015% and entrapment efficiency of 89.32±0.34%. The plasma AUC (0-t), t 1/2 and C max of CUR micelles were increased by 52.8, 4.63 and 7.51-fold compared to the CUR solution, respectively. In vivo results showed that multiple injections of CUR-loaded micelles could prolong the circulation time and increase the therapeutic efficacy of CUR. These results suggested that mPEG-PCL micelles would be a potential carrier for CUR. Copyright © 2016 Elsevier B.V. All rights reserved.
Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

PubMed

Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

2016-11-01

Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Serine protease activity of Cur l 1 from Curvularia lunata augments Th2 response in mice.

PubMed

Tripathi, Prabhanshu; Kukreja, Neetu; Singh, B P; Arora, Naveen

2009-05-01

Studies with mite allergens demonstrated that proteolytic activity augments allergic airway inflammation. This knowledge is limited to few enzyme allergens. The objective of this study is to investigate the effect of serine protease Cur l 1 from Curvularia lunata in airway inflammation/hyper-responsiveness. Cur l 1 was purified and inactivated using a serine protease inhibitor. Balb/c mice were sensitized with enzymatically active Cur l 1 or C. lunata extract. Sensitized mice were given booster dose on day 14 with active or inactivated Cur l 1. Intranasal challenge was given on day 28, 29, and 30. Airway hyper-responsiveness was measured by plethysmography. Blood, bronchoalveolar lavage fluid (BALF), spleen, and lungs from mice were analyzed for cellular infiltration, immunoglobulins, and cytokine levels. Mice challenged with enzymatically active Cur l 1 demonstrated significantly higher airway inflammation than inactive Cur l 1 group mice (p < 0.01). There was a significant difference in serum IgE and IgG1 levels among mice immunized with active Cur l 1 and inactive Cur l 1 (p < 0.01). IL-4 and IL-5 were higher in BALF and splenocyte culture supernatant of active Cur l 1 than inactive Cur l 1 mice. Lung histology revealed increased eosinophil infiltration, goblet cell hyperplasia and mucus secretion in active group. Proteolytic activity of Cur l 1 plays an important role in airway inflammation and the inactivated Cur l 1 has potential to be explored for immunotherapy.
Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer

NASA Astrophysics Data System (ADS)

Zhang, Yumin; Yang, Cuihong; Wang, Weiwei; Liu, Jinjian; Liu, Qiang; Huang, Fan; Chu, Liping; Gao, Honglin; Li, Chen; Kong, Deling; Liu, Qian; Liu, Jianfeng

2016-02-01

Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.
Curcumin-guided nanotherapy: a lipid-based nanomedicine for targeted drug delivery in breast cancer therapy.

PubMed

Lin, Mingzhen; Teng, Lili; Wang, Yang; Zhang, Jiaxin; Sun, Xianglian

2016-05-01

Delivery of anti-cancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment. In this study, folate (FA) decorated nanostructured lipid carriers (NLCs) were constructed as nanomedicine for the delivery of curcumin (CUR). CUR-loaded NLCs (CUR-NLCs) were prepared. FA containing polyethylene glycol (PEG)-distearoylphosphatidylethanolamine (DSPE) (FA-PEG-DSPE) was synthesized and used for the decoration of CUR-NLCs. Their particle size, zeta potential, and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study FA decorated CUR-NLCs (FA-CUR-NLCs) was tested in MCF-7 human breast cancer cells (MCF-7 cells). In vivo anti-tumor efficacies of the carriers were evaluated on mice bearing breast cancer model. The optimum FA-CUR-NLCs formulations with the particle size of 127 nm and with a +13 mV surface charge. The growth of MCF-7 cells in vitro was obviously inhibited. FA-CUR-NLCs also displayed the best anti-tumor activity than other formulations in vivo. The results demonstrated that FA-CUR-NLCs were efficient in selective delivery to cancer cells over-expressing FA receptors (FRs). Also FA-CUR-NLCs transfer CUR to the breast cancer cells, enhance the anti-tumor capacity. Thus, FA-CUR-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.
Adherence of curli producing Shiga-toxigenic Escherichia coli to baby spinach leaves

USDA-ARS?s Scientific Manuscript database

Cellular appendages, such as curli fibers have been suggested to be involved in STEC persistence in fresh produce as these curli are critical in biofilm formation and adherence to animal cells. We determined the role of curli in attachment of STEC on spinach leaves. The curli expression by wild-ty...
Iodinated curcumin bearing dermal cream augmented drug delivery, antimicrobial and antioxidant activities.

PubMed

Manchanda, Gagandeep; Sodhi, Rupinder Kaur; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

2018-01-01

Curcumin (Cur) exhibits weak microbicidal activity owing to high lipophilicity and low cell permeability. Therefore, in the present investigation, Cur was iodinated using elemental iodine (I 2 ) to synthesise Cur-I 2 powder that was later formulated as Cur-I 2 dermal cream and characterised in vitro for antimicrobial and antioxidant activities. Electrophilic addition of I 2 saturated the olefinic bonds of Cur, as confirmed by UV/visible spectroscopy, FT-IR, 1 H NMR and DSC techniques. In addition, in vitro skin permeation and retention analysis indicated that Cur-I 2 cream followed the first order and Higuchi model for drug release through the rat skin. The minimum inhibitory concentration (MIC) of Cur-I 2 powder was measured to be 60 and 90 µg/ml significantly (p < 0.05) lower than 150 and 120 µg/ml of Cur against Staphylococcus aureus and Escherichia coli, respectively. Moreover, Cur-I 2 also exhibited strong antioxidant potential. Cur-I 2 cream warrants further in vivo study to scale up the technology for clinical translation.
Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Bauer, Nichole A; Chauhan, Neeraj; Kumar, Deepak; Jaggi, Meena; Chauhan, Subhash C

2012-01-01

The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed. MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated. MNP-CUR exhibited individual particle grain size of ~9 nm and hydrodynamic average aggregative particle size of ~123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR. MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.
Bending energy penalty enhances the adhesive strength of functional amyloid curli to surfaces

NASA Astrophysics Data System (ADS)

Zhang, Yao; Wang, Ao; DeBenedictis, Elizabeth P.; Keten, Sinan

2017-11-01

The functional amyloid curli fiber, a major proteinaceous component of biofilm extracellular matrices, plays an important role in biofilm formation and enterobacteriaceae adhesion. Curli nanofibers exhibit exceptional underwater adhesion to various surfaces, have high rigidity and strong tensile mechanical properties, and thus hold great promise in biomaterials. The mechanisms of how curli fibers strongly attach to surfaces and detach under force remain elusive. To investigate curli fiber adhesion to surfaces, we developed a coarse-grained curli fiber model, in which the protein subunit CsgA (curli specific gene A) self-assembles into the fiber. The coarse-grained model yields physiologically relevant and tunable bending rigidity and persistence length. The force-induced desorption of a single curli fiber is examined using coarse-grained modeling and theoretical analysis. We find that the bending energy penalty arising from high persistence length enhances the resistance of the curli fiber against desorption and thus strengthens the adhesion of the curli fiber to surfaces. The CsgA-surface adhesion energy and the curli fiber bending rigidity both play crucial roles in the resistance of curli fiber against desorption from surfaces. To enable the desorption process, the applied peeling force must overcome both the interfacial adhesion energy and the energy barrier for bending the curli fiber at the peeling front. We show that the energy barrier to desorption increases with the interfacial adhesion energy, however, the bending induced failure of a single curli fiber limits the work of adhesion if the proportion of the CsgA-surface adhesion energy to the CsgA-CsgA cohesive energy becomes large. These results illustrate that the optimal adhesion performance of nanofibers is dictated by the interplay between bending, surface energy and cohesive energy. Our model provides timely insight into enterobacteriaceae adhesion mechanisms as well as future designs of engineered curli fiber based adhesives.
Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells.

PubMed

Dash, Tapan K; Konkimalla, V Badireenath

2017-02-01

Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells. Four different curcumin formulations were prepared namely DMSO assisted curcumin nano-dispersion (CurD, 260 nm), liposomal curcumin (CurL, 165 nm), MPEG-PCL micellar curcumin (CurM, 18 nm) and cyclodextrin encapsulated curcumin (CurN, 37 nm). The formulations were subjected to particle characterizations (size, zeta potential, release studies), followed by biological assays such as cellular uptake, P-gp inhibitory activity and reversal of DOX resistance by co-treatment with DOX. Curcumin uptake in K562N and K562R cells was mildly reduced when treated with CurL and CurM, while for CurD and CurN the uptake remained equivalent. However, CurL retained P-gp inhibitory activity of curcumin and with a considerable chemo-sensitizing effect but CurM showed no P-gp inhibitory activity. CurN retained above biological activities, but requires a secondary carrier under in vivo conditions. From the results, CurM was found to be most suitable for solubilization of curcumin where as CurL can be considered as most suitable nano-formulation for reversal of DOX resistance.
Natural rpoS mutations contribute to population heterogeneity in Escherichia coli O157:H7 strains linked to the 2006 US spinach-associated outbreak.

PubMed

Carter, Michelle Qiu; Louie, Jacqueline W; Huynh, Steven; Parker, Craig T

2014-12-01

We previously reported significantly different acid resistance between curli variants derived from the same Escherichia coli O157:H7 strain, although the curli fimbriae were not associated with this phenotypic divergence. Here we investigated the underlying molecular mechanism by examining the genes encoding the common transcriptional regulators of curli biogenesis and acid resistance. rpoS null mutations were detected in all curli-expressing variants of the 2006 spinach-associated outbreak strains, whereas a wild-type rpoS was present in all curli-deficient variants. Consequently curli-expressing variants were much more sensitive to various stress challenges than curli-deficient variants. This loss of general stress fitness appeared solely to be the result of rpoS mutation since the stress resistances could be restored in curli-expressing variants by a functional rpoS. Comparative transcriptomic analyses between the curli variants revealed a large number of differentially expressed genes, characterized by the enhanced expression of metabolic genes in curli-expressing variants, but a marked decrease in transcription of genes related to stress resistances. Unlike the curli-expressing variants of the 1993 US hamburger-associated outbreak strains (Applied Environmental Microbiology 78: 7706-7719), all curli-expressing variants of the 2006 spinach-associated outbreak strains carry a functional rcsB gene, suggesting an alternative mechanism governing intra-strain phenotypic divergence in E. coli O157:H7. Published by Elsevier Ltd.
Curcumin complexation with cyclodextrins by the autoclave process: Method development and characterization of complex formation.

PubMed

Hagbani, Turki Al; Nazzal, Sami

2017-03-30

One approach to enhance curcumin (CUR) aqueous solubility is to use cyclodextrins (CDs) to form inclusion complexes where CUR is encapsulated as a guest molecule within the internal cavity of the water-soluble CD. Several methods have been reported for the complexation of CUR with CDs. Limited information, however, is available on the use of the autoclave process (AU) in complex formation. The aims of this work were therefore to (1) investigate and evaluate the AU cycle as a complex formation method to enhance CUR solubility; (2) compare the efficacy of the AU process with the freeze-drying (FD) and evaporation (EV) processes in complex formation; and (3) confirm CUR stability by characterizing CUR:CD complexes by NMR, Raman spectroscopy, DSC, and XRD. Significant differences were found in the saturation solubility of CUR from its complexes with CD when prepared by the three complexation methods. The AU yielded a complex with expected chemical and physical fingerprints for a CUR:CD inclusion complex that maintained the chemical integrity and stability of CUR and provided the highest solubility of CUR in water. Physical and chemical characterizations of the AU complexes confirmed the encapsulated of CUR inside the CD cavity and the transformation of the crystalline CUR:CD inclusion complex to an amorphous form. It was concluded that the autoclave process with its short processing time could be used as an alternate and efficient methods for drug:CD complexation. Copyright © 2017 Elsevier B.V. All rights reserved.
A DEIM Induced CUR Factorization

DTIC Science & Technology

2015-09-18

CUR approximate matrix factorization based on the Discrete Empirical Interpolation Method (DEIM). For a given matrix A, such a factorization provides a...CUR approximations based on leverage scores. 1 Introduction This work presents a new CUR matrix factorization based upon the Discrete Empirical...SUPPLEMENTARY NOTES 14. ABSTRACT We derive a CUR approximate matrix factorization based on the Discrete Empirical Interpolation Method (DEIM). For a given
Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy

PubMed Central

Trigo Gutierrez, Jeffersson Krishan; Zanatta, Gabriela Cristina; Ortega, Ana Laura Mira; Balastegui, Maria Isabella Cuba; Sanitá, Paula Volpato; Pavarina, Ana Cláudia; Barbugli, Paula Aboud

2017-01-01

Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR. PMID:29107978
Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity.

PubMed

Popat, Amirali; Karmakar, Surajit; Jambhrunkar, Siddharth; Xu, Chun; Yu, Chengzhong

2014-05-01

Curcumin (CUR), a naturally derived anti-cancer cocktail is arguably the most widely studied neutraceutical. Despite a lot of promises, it is yet to reach the market as an active anti-cancer formulation. In the present study, we have prepared highly soluble (3 mg/ml) CUR-γ-hydroxypropyl cyclodextrin (CUR-CD) hollow spheres. CUR-CD hollow spheres were prepared by a novel and scalable spray drying method. CUR-CD was then encapsulated into positively charged biodegradable chitosan (CUR-CD-CS) nanoparticles. The CUR-CD-CS nanoparticles were characterised by TEM, SEM, DLS, drug loading and in vitro release. We tested the efficacy of these CUR-CD-CS nanoparticles in SCC25 cell lines using MTT assay and investigated its cellular uptake mechanism. We also studied Oligo DNA loading in CUR-CD-CS nanoparticles and its delivery via confocal imaging and FACS analysis. Our results demonstrated that CUR-CD-CS nanoparticles showed superior in vitro release performance and higher cytotoxicity in SCC25 cell line amongst all tested formulations. The cytotoxicity results were corroborated by cell cycle analysis and apoptosis test, showing nearly 100% apoptotic cell death in the case of CUR-CD-CS nanoparticles. Compared to CS nanoparticles, CS-CD nanoformulation showed higher cellular delivery of Cy3-Oligo DNA which was tested quantitatively using flowcytometry analysis, indicating that CD not only enhanced CUR solubility but also boosted the cellular uptake. Our study shows that rationally designed bio-degradable natural biomaterials have great potential as next generation nano-carriers for hydrophobic drug delivery such as CUR with potential of dual drug-gene delivery. Copyright © 2014 Elsevier B.V. All rights reserved.
Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy.

PubMed

Xie, Jiajiang; Fan, Zhongxiong; Li, Yang; Zhang, Yinying; Yu, Fei; Su, Guanghao; Xie, Liya; Hou, Zhenqing

2018-01-01

We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy. A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff's base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR). The prepared MTX-Imine-M-CUR nanoparticles were composed of an inner hydrophobic DSPE/CUR core and an outside hydrophilic bishydroxyl poly (ethyleneglycol) (PEG) shell with a self-targeting MTX prodrug corona. The imine linker between 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethyleneglycol)-2000] and MTX, as a dynamic covalent bond, was strong enough to remain intact in physiological pH, even though it is rapidly cleaved in acidic pH. The MTX-Imine-M-CUR could codeliver MTX and CUR selectively and efficiently into the cancer cells via folate receptor-mediated endocytosis followed by the rapid intracellular release of CUR and the active form of MTX via the acidity of endosomes/lysosomes. Moreover, the MTX-Imine-M-CUR resulted in significantly higher in vitro and in vivo anticancer activity than pH-insensitive DSPE-PEGAmide-MTX assembling nanoparticles loaded with CUR (MTX-Amide-M-CUR), MTX unconjugated DSPE-PEG assembling micellar nanoparticles loaded with CUR (M-CUR), combination of both free drugs, and individual free drugs. The smart system provided a simple, yet feasible, drug delivery strategy for targeted combination chemotherapy.
A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability.

PubMed

Wang, Yutong; Wang, Changyuan; Zhao, Jing; Ding, Yanfang; Li, Lei

2017-01-01

Nanosuspension is one of the most promising strategies to improve the oral bioavailability of insoluble drugs. The existing techniques applied to produce nanosuspensions are classified as "bottom-up" or "top-down" methods, or a combination of both. Curcumin (CUR), a Biopharmaceutics Classification System (BCS) class IV substance, is a promising drug candidate in view of its good bioactivity, but its use is limited due to its poor solubility and permeability. In the present study, CUR nanosuspensions were developed to enhance CUR oral bioavailability using a cost-effective method different from conventional techniques. The physicochemical properties of CUR nanosuspensions were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The crystalline state of CUR in different nanosuspensions analyzed using differential scanning calorimeter (DSC) and X-ray diffraction analysis (PXRD) confirmed its amorphous state. In vitro dissolution degree of the prepared CUR nanosuspensions using TPGS or Brij78 as stabilizer was greatly increased. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 3.18 and 3.7 times after administration of CUR/TPGS nanosuspensions or CUR/Brij78 nanosuspensions, when compared with the administration of CUR suspension. CUR nanosuspensions produced by our cost-effective method could improve its oral bioavailability. In addition, the low-cost and time-saving method reported here is highly suitable for a fast and inexpensive preparation. Copyright © 2016 Elsevier Inc. All rights reserved.
Visible Light-Cured Glycol Chitosan Hydrogel Containing a Beta-Cyclodextrin-Curcumin Inclusion Complex Improves Wound Healing In Vivo.

PubMed

Yoon, Sun-Jung; Hyun, Hoon; Lee, Deok-Won; Yang, Dae Hyeok

2017-09-10

Scarless wound healing is ideal for patients suffering from soft tissue defects. In this study, we prepared a novel wet dressing (β-CD-ic-CUR/GC) based on the visible light-cured glycol chitosan (GC) hydrogel and inclusion complex between beta-cyclodextrin (β-CD) and curcumin (CUR). We also evaluated its efficacy in the acceleration of wound healing as compared to that of CUR-loaded GC (CUR/GC). The conjugation of glycidyl methacrylate (GM) to GC for photo-curing was confirmed by ¹H-NMR measurement, and the photo-cured GC hydrogel was characterized by the analyses of rheology, swelling ratio, SEM and degradation rate. After visible light irradiation, the surface/cross-sectional morphologies and storage (G')/loss (G'') moduli revealed the formation of hydrogel with interconnected porosity. The dressing β-CD-ic-CUR/GC exhibited a controlled release of 90% CUR in a sustained manner for 30 days. On the other hand, CUR/GC showed CUR release of 16%. β-CD acted as an excipient in improving the water-solubility of CUR and affected the release behavior of CUR. The in vivo animal tests including measurement of the remaining unhealed wound area and histological analyses showed that β-CD-ic-CUR/GC may have potential as a wet dressing agent to enhance soft tissue recovery in open fractures.
Problems encountered by BA Cur graduates and recommendations for enhancing learner support.

PubMed

Ehlers, V

2000-12-01

Distance education is becoming ever more important in providing continuing post basic, and especially postgraduate, education to practising professional persons, including nurses. As more and more institutions in the Republic of South Africa offer distance education courses to nurses, it is essential to take note of the positive and negative experiences of successful graduates of these programmes, in order to enhance the learning opportunities, and the success rate of nurses pursuing such distance education courses. A brief historical overview is provided about the University of South Africa (Unisa) and about the Department of Advanced Nursing Sciences at this distance education university. This background information should assist the reader in contextualising the research findings. Questionnaires were posted to all Unisa's 1998 BA Cur graduates. The research report focuses on the 1998 BA Cur (nursing) graduates' biographic data, their experiences of pursuing distance education post basic nursing courses, their positive and negative perceptions of these experiences and their recommendations for enhancing other students' success.
Expression of Curli by Escherichia coli O157:H7 Strains Isolated from Patients during Outbreaks Is Different from Similar Strains Isolated from Leafy Green Production Environments.

PubMed

Ravva, Subbarao V; Sarreal, Chester Z; Cooley, Michael B

2016-01-01

We previously reported that the strains of Escherichia coli O157:H7 (EcO157) that survived longer in austere soil environment lacked expression of curli, a fitness trait linked with intestinal colonization. In addition, the proportion of curli-positive variants of EcO157 decreased with repeated soil exposure. Here we evaluated 84 and 176 clinical strains from outbreaks and sporadic infections in the US, plus 211 animal fecal and environmental strains for curli expression. These shiga-toxigenic strains were from 328 different genotypes, as characterized by multi-locus variable-number tandem-repeat analysis (MLVA). More than half of the fecal strains (human and animal) and a significant proportion of environmental isolates (82%) were found to lack curli expression. EcO157 strains from several outbreaks linked with the consumption of contaminated apple juice, produce, hamburgers, steak, and beef were also found to lack curli expression. Phylogenetic analysis of fecal strains indicates curli expression is distributed throughout the population. However, a significant proportion of animal fecal isolates (84%) gave no curli expression compared to human fecal isolates (58%). In addition, analysis of environmental isolates indicated nearly exclusive clustering of curli expression to a single branch of the minimal spanning tree. This indicates that curli expression depends primarily upon the type of environmental exposure and the isolation source, although genotypic differences also contribute to clonal variation in curli. Furthermore, curli-deficient phenotype appears to be a selective trait for survival of EcO157 in agricultural environments.
Effects of chitosan molecular weight on the physical and dissolution characteristics of amorphous curcumin-chitosan nanoparticle complex.

PubMed

Yu, Hong; Nguyen, Minh-Hiep; Hadinoto, Kunn

2018-01-01

To investigate the effects of varying molecular weight (MW) of chitosan (CHI) used in the complexation with curcumin (CUR) on the physical and dissolution characteristics of the amorphous CUR-CHI nanoparticle complex produced. Amorphous CUR-CHI nanoparticle complex (or CUR nanoplex in short) recently emerged as a promising bioavailability enhancement strategy of CUR attributed to its fast dissolution, supersaturation generation capability, and simple preparation. Existing CUR nanoplex prepared using low MW CHI, however, exhibited poor colloidal stability during storage. Herein we hypothesized that the colloidal stability could be improved by using CHI of higher MW. The effects of this approach on the nanoplex's other characteristics were simultaneously investigated. The CUR nanoplex was prepared by electrostatically driven self-assembled complexation between CUR and oppositely charged CHI of three different MWs (i.e. low, medium, and high). Besides colloidal stability, the effects of MW variation were investigated for the nanoplex's (1) other physical characteristics (i.e. size, zeta potential, CUR payload, amorphous state stability), (2) preparation efficiency (i.e. CUR utilization rate, yield), and (3) dissolutions under sink condition and supersaturation generation. CUR nanoplex prepared using CHI of high MW exhibited improved colloidal stability, larger size, superior morphology, and prolonged supersaturation generation. On the other hand, the effects of MW variation on the payload, amorphous state stability, preparation efficiency, and dissolution under sink condition were found to be insignificant. Varying MW of CHI used was an effective means to improve certain aspects of the CUR nanoplex characteristics with minimal adverse effects on the others.
Enhanced Bioavailability and Anticancer Effect of Curcumin-Loaded Electrospun Nanofiber: In Vitro and In Vivo Study

NASA Astrophysics Data System (ADS)

Wang, Chuan; Ma, Chao; Wu, Zhenkai; Liang, He; Yan, Peng; Song, Jia; Ma, Nan; Zhao, Qinghua

2015-11-01

Nanofibers have attracted increasing attention in drug delivery and other biomedical applications due to their some special properties. The present study aims to prepare a fiber-based nanosolid dispersion system to enhance the bioavailability of curcumin (CUR). CUR-loaded polyvinyl pyrrolidone (CUR@PVP) nanofibers were successfully prepared via electrospinning. Scanning electron microscopy (SEM) was employed to observe the morphology of the nanofibers, and the SEM image showed that the drug-loaded nanofibers were smooth, and no CUR clusters were found on the surface of the nanofibers. The results of X-ray diffraction (XRD) demonstrated that the CUR was evenly distributed in the nanofibers in an amorphous state. Fourier transform infrared (FTIR) spectroscopy analysis indicated that intermolecular hydrogen bonding occurred between the CUR and the polymer matrix. In vitro dissolution profiles showed that CUR@PVP nanofiber could be quickly dissolved in phosphate-buffered saline (PBS) solution, while negligible dissolution was observed in pure CUR sample. Importantly, in vitro cell viability assays and in vivo animal tests revealed that the nanosolid dispersion system dramatically enhanced the bioavailability and showed effective anticancer effect of the CUR.

Galactosylated pullulan-curcumin conjugate micelles for site specific anticancer activity to hepatocarcinoma cells.

PubMed

Sarika, P R; James, Nirmala Rachel; Nishna, N; Anil Kumar, P R; Raj, Deepa K

2015-09-01

Galactosylated pullulan-curcumin conjugate (LANH2-Pu Ald-Cur SA) is developed for target specific delivery of curcumin to hepatocarcinoma cells by five step synthetic strategy, which includes oxidation of pullulan (Pu Ald), introduction of amino group to the targeting ligand (LANH2), grafting of the LANH2 to Pu Ald, modification of curcumin (Cur SA) and conjugation of Cur SA to pullulan. Nongalactosylated pullulan-curcumin conjugate (Pu-Cur SA) is also prepared to compare the enhancement in cytotoxicity offered by the targeting group. Both LANH2-Pu Ald-Cur SA and Pu-Cur SA conjugates could self assemble to micelle in water with hydrodynamic diameters of 355±9nm and 363±10nm, respectively. Both conjugates show spherical morphology and enhance stability of curcumin in physiological pH. Compared to Pu-Cur SA, LANH2-Pu Ald-Cur SA exhibits higher toxicity and internalization towards HepG2 cells. This indicates the enhanced uptake of LANH2-Pu Ald-Cur SA conjugate via ASGPR (asialoglycoprotein receptor) mediated endocytosis into HepG2 cells. Copyright © 2015 Elsevier B.V. All rights reserved.
Adapting current Arden Syntax knowledge for an object oriented event monitor.

PubMed

Choi, Jeeyae; Lussier, Yves A; Mendoça, Eneida A

2003-01-01

Arden Syntax for Medical Logic Module (MLM)1 was designed for writing and sharing task-specific health knowledge in 1989. Several researchers have developed frameworks to improve the sharability and adaptability of Arden Syntax MLMs, an issue known as "curly braces" problem. Karadimas et al proposed an Arden Syntax MLM-based decision support system that uses an object oriented model and the dynamic linking features of the Java platform.2 Peleg et al proposed creating a Guideline Expression Language (GEL) based on Arden Syntax's logic grammar.3 The New York Presbyterian Hospital (NYPH) has a collection of about 200 MLMs. In a process of adapting the current MLMs for an object-oriented event monitor, we identified two problems that may influence the "curly braces" one: (1) the query expressions within the curly braces of Arden Syntax used in our institution are cryptic to the physicians, institutional dependent and written ineffectively (unpublished results), and (2) the events are coded individually within a curly braces, resulting sometimes in a large number of events - up to 200.
Curcumin-encapsulated polymeric micelles suppress the development of colon cancer in vitro and in vivo.

PubMed

Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng; Gong, Changyang

2015-05-18

To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.
Enhanced 4T1 breast carcinoma anticancer activity by co-delivery of doxorubicin and curcumin with core-shell drug-carrier based on heparin modified poly(L-lactide) grafted polyethylenimine cationic nanoparticles.

PubMed

Guo, Oingfa; Li, Xiaolu; Yang, Yi; Wei, Jing; Zhao, Qian; Luo, Feng; Qian, Zhiyong

2014-02-01

Use of single chemotherapy agents has shown some limitations in anti-tumor treatment, such as development of drug resistance, severe adverse reactions and limited regime for therapeutic use. Combination of two or more therapeutic drugs is a feasible strategy to overcome these limitations. This paper reports study of co-delivery by core-shell nanoparticles (NPs) with hydrophobic PLLA core loaded with curcumin (Cur) and hydrophilic heparin shell adsorbing Doxorubicin (DOX). Characterizations of Cur-PEA NPs, Cur-PEA/heparin NPs and DOX adsorbing into Cur-PEA/heparin NPs (DOX-Cur NPs) were also investigated by transmission electron microscope (TEM) and Malvern Zetasizer. Studies on cellular uptake of DOX-Cur NPs demonstrated that both drugs were effectively taken up by 4T1 tumor cells. Furthermore, DOX-Cur NPs suppressed 4T1 tumor cells growth more efficiently than either DOX or Cur alone at the same concentrations, as measured by flow cytometry (FCM). We found out that intravenous injection of DOX-Cur NPs efficiently inhibited growth of subcutaneous 4T1 breast carcinoma in vivo (p < 0.01) and prolonged survival of the treated 4T1 breast carcinoma mice. Moreover, the pathological damage to the cardiac tissue in mice treated with DOX-Cur NPs was significantly less severe than that of mice treated with free DOX. This study suggested that DOX-Cur NPs may have promising applications in breast carcinoma therapy.
Curcumin protects against cigarette smoke-induced cognitive impairment and increased acetylcholinesterase activity in rats.

PubMed

Jaques, Jeandre Augusto dos Santos; Rezer, João Felipe Peres; Carvalho, Fabiano Barbosa; da Rosa, Michelle Melgarejo; Gutierres, Jessié Martins; Gonçalves, Jamile Fabbrin; Schmatz, Roberta; de Bairros, André Valle; Mazzanti, Cinthia Melazzo; Rubin, Maribel Antonello; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

2012-07-16

Cigarette smoke, a widely spread habit, is associated with a decline in cognitive function and studies have demonstrated that curcumin (Cur), an Indian spice, possesses a strong neuroprotective potential. Considering the relevance of investigating dietary compounds this study aimed to investigate the effect of Cur on memory and acetylcholinesterase (AChE) activity in brain structures and blood of cigarette smoke-exposed rats. Male Wistar rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. The experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: Vehicle (corn oil), Cur 12.5 mg/kg, Cur 25 mg/kg and Cur 50 mg/kg. In the second, the animals were divided into 5 groups: Vehicle (corn oil), Smoke, Smoke plus Cur 12.5 mg/kg, Smoke plus Cur 25 mg/kg and Smoke plus Cur 50 mg/kg. Treatment with Cur significantly prevented the decreased latency and cholinergic alterations in cigarette smoke-exposed rats. These AChE alterations could suggest a role in the memory impairment promoted by cigarette smoke-exposure and point toward the potential of Cur to modulate cholinergic neurotransmission and, consequently, improve cognition deficits induced by smoke. This study suggests that the dietary compound Cur may be involved in cholinergic system modulation and as a consequence exert an effect on learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.
Medical Surveillance Monthly Report (MSMR). Volume 1, Number 3, June 1995

DTIC Science & Technology

1995-06-01

Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 MSMR2 June, 1995 Executive Editor COL John F. Brundage, MD, MPH Director, Epidemiology ...neces- sarily those of the Department of the Army. Prepared by the Medical Surveil- lance Activity, Directorate of Epidemiology and Disease...Gonorrhea Herpes Simplex Syphilis Prim/Sec Syphilis Latent Urethritis non-spec. Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur
Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles for Cervical Cancer Therapy: Formulation, Characterization, and InVitro and InVivo Evaluation.

PubMed

Wang, Jiao; Liu, Qiang; Yang, Linnan; Xia, Xiaofei; Zhu, Rongrong; Chen, Shengguang; Wang, Mei; Cheng, Liming; Wu, Xianzheng; Wang, Shilong

2017-12-01

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.
Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

PubMed

Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

2015-01-01

Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.
Curcumin Delivery by Poly(Lactide)-Based Co-Polymeric Micelles: An In Vitro Anticancer Study.

PubMed

Kumari, Preeti; Swami, Muddineti Omkara; Nadipalli, Sravan Kumar; Myneni, Srividya; Ghosh, Balaram; Biswas, Swati

2016-04-01

This work describes the synthesis of block co-polymeric micelles, methoxy-poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA) to encapsulate Curcumin (CUR), thereby improving the dispersibility and chemical stability of curcumin, prolonging its cellular uptake and enhancing its bioavailability. CUR-mPEG-PLA micelles, was prepared using the thin-film hydration method and evaluated in vitro. The preparation process was optimized with a central composite design (CCD). Micelles were characterized by size, transmission electron microscopy, loading capacity, and critical micelle concentration (CMC). The cytotoxicity of CUR-mPEG-PLA micelles was investigated against murine melanoma cells, B16F10 and human breast cancer cells, MDA-MB-231. The average size of the CUR-mPEG-PLA micelles was 110 ± 5 nm with polydispersity index in the range of 0.15-0.31, and the encapsulating efficiency for CUR was 91.89 ± 1.2, and 11.06 ± 0.8% for drug-loading. Sustained release of CUR from micelles was observed with 9.73% CUR release from micelles compared to 64.24% release of free curcumin in first 6 h under sink condition. The CUR-mPEG-PLA was efficiently taken up by the cancer cells, B16F10 and MDA-MB-231. Following 24 h incubation, CUR-mPEG-PLA induced higher cytotoxicity compared to free CUR in MDA-MB-231 cell lines indicating exposure of higher dose of free CUR to cells lead to up-regulation of drug efflux mechanisms leading to decreased cell death in case of free CUR administration. Our results indicate that the proposed micellar system has the potential to serve as an efficient carrier for CUR by effectively solubilizing, stabilizing and delivering the drug in a controlled manner to the cancer cells.
Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer

PubMed Central

Zhu, Wen-Ting; Liu, Sheng-Yao; Wu, Lei; Xu, Hua-Li; Wang, Jun; Ni, Guo-Xin; Zeng, Qing-Bing

2017-01-01

Background It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA) polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI) in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the migration and invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG–PLA micelles inhibited human umbilical vein endothelial cells migration, invasion and corresponding tube formation, implying the antiangiogenesis ability. Its enhanced antitumor mechanism may be related to the reduced expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as well as the increased expression of Bax. Conclusion The mPEG–PLA copolymer micelles can serve as an efficient carrier for CUR. The CUR/mPEG–PLA micelles have promising clinical potential in treating NSCLC. PMID:28435247
Preparation of curcumin self-micelle solid dispersion with enhanced bioavailability and cytotoxic activity by mechanochemistry.

PubMed

Zhang, Qihong; Polyakov, Nikolay E; Chistyachenko, Yulia S; Khvostov, Mikhail V; Frolova, Tatjana S; Tolstikova, Tatjana G; Dushkin, Alexandr V; Su, Weike

2018-11-01

An amorphous solid dispersion (SD) of curcumin (Cur) with disodium glycyrrhizin (Na 2 GA) was prepared by mechanical ball milling. Curcumin loaded micelles were self-formed by Na 2 GA when SD dissolved in water. The physical properties of Cur SD in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscope. The characteristics of the sample solutions were analyzed by reverse phase HPLC, UV-visible spectroscopy, 1 H NMR spectroscopy, gel permeation LC, and transmission electron microscopy. In vitro cytotoxic tests demonstrated that Cur SD induced higher cytotoxicity against glioblastoma U-87 MG cells than free Cur. Besides, an improvement of membrane permeability of Cur SD was confirmed by parallel artificial membrane permeability assay. Further pharmacokinetic study of this SD formulation in rat showed a significant ∼19-fold increase of bioavailability as comparing to free Cur. Thus, Cur SD provide a more potent and efficacious formulation for Cur oral delivery.
CD44-targeted hyaluronic acid-curcumin prodrug protects renal tubular epithelial cell survival from oxidative stress damage.

PubMed

Hu, Jing-Bo; Li, Shu-Juan; Kang, Xu-Qi; Qi, Jing; Wu, Jia-Hui; Wang, Xiao-Juan; Xu, Xiao-Ling; Ying, Xiao-Ying; Jiang, Sai-Ping; You, Jian; Du, Yong-Zhong

2018-08-01

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H 2 O 2 -pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.
(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markham, Jack; Liang, Jun; Levina, Aviva

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less
(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

DOE PAGES

Markham, Jack; Liang, Jun; Levina, Aviva; ...

2017-01-23

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less
Curly Top Disease of Tomato

USDA-ARS?s Scientific Manuscript database

Curly top disease, caused by viruses in the genus, Curtovirus, has impacted western US agriculture for over a century; and is a significant threat to tomato production. The two most abundant curtovirus species today are Beet severe curly top virus (BSCTV) and Beet mild curly top virus (BMCTV) but ot...
Solid Dispersion of Curcumin as Polymeric Films for Bioenhancement and Improved Therapy of Rheumatoid Arthritis.

PubMed

Mande, Prashant P; Bachhav, Sagar S; Devarajan, Padma V

2016-08-01

The aim of our study was development of advanced third generation Curcumin self microemulsifying composition solid dispersion (Cur SMEC-SD) with high drug loading, improved stability, rapid in-vitro dissolution and enhanced bioavailability for improved therapy of rheumatoid arthritis. The Cur SMEC-SD comprising polymers (KollidonVA64[KVA], Eudragits, HPMC and Soluplus) and self microemulsifying composition of surfactant:co-surfactant:oil were coated onto rapidly disintegrating inert tablet core. SDs evaluated for stability, in-vitro release and bioenhancement. Cur SMEC-SDs exhibited high Cur loading of 45% w/w and microemulsion formation with globule size (~100 nm) irrespective of polymers. Among the polymers, SD with KVA revealed exceptionally low contact angle (7°C) and rapid in-vitro release (t50%-6.45 min). No crystallization was evident as confirmed by SEM, DSC and XRD and is attributed to SMEC aided solubilization/amorphisation, and interaction of KVA with Cur seen in the FTIR spectra. Stability was confirmed as per ICH guidelines. Remarkable bioenhancement with Cur SMEC-SD was confirmed by the > four fold and a two fold compared to Cur and Cur-SD without SMEC respectively. High efficacy ~ 80% compared to Indomethacin, seen with rheumatoid arthritis (RA) induced rats coupled with no adverse toxicity. The advanced third generation Cur SMEC-SD presents a practical technological advancement and suggests Cur SMEC-SD as promising alternative for RA therapy.
Mitogen-activated protein kinase Hog1 is activated in response to curcumin exposure in the budding yeast Saccharomyces cerevisiae.

PubMed

Azad, Gajendra Kumar; Singh, Vikash; Thakare, Mayur Jankiram; Baranwal, Shivani; Tomar, Raghuvir Singh

2014-12-19

Curcumin (CUR), an active polyphenol derived from the spice turmeric, has been traditionally used for centuries in ancient Indian medicine to treat a number of diseases. The physiological effects of CUR have been shown to be diverse; however, the target molecules and pathways that CUR affects have yet to be fully described. Here, we demonstrate for the first time that the budding yeast mitogen-activated protein kinase (MAPK) Hog1 is essential for the response to CUR. Moreover, CUR-induced Hog1 phosphorylation was rescued by supplementation of iron to the growth medium. Hog1 was rapidly phosphorylated upon CUR treatment, but unlike the response to hyperosmotic shock (0.8 M NaCl), it remains activated for an extended period of time. A detailed analysis of HOG pathway mutants revealed that Pbs2p, Ptc2p, and Ssk2p are required for optimal CUR-induced Hog1 phosphorylation. We also observed a Hog1 dependent transcriptional response to CUR treatment that involved the up-regulation of glycerol-3-phosphate dehydrogenase 1 (GPD1), a factor that is essential for the hyperosmotic stress response. Our present finding revealed the role of Hog1 MAPK in regulation of CUR-induced transcriptional response. We anticipate that our finding will enhance the understanding on the molecular mode of action of CUR on S. cerevisiae.
Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

PubMed

Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

2014-01-01

Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p < 0.001 for TOS and OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p < 0.001 for all comparisons). Histopathological examination revealed less severe lesions in CUR group than in the control group. CUR administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta I/R rat model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy

NASA Astrophysics Data System (ADS)

Xiao, Bo; Han, Moon Kwon; Viennois, Emilie; Wang, Lixin; Zhang, Mingzhen; Si, Xiaoying; Merlin, Didier

2015-10-01

Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy. Electronic supplementary information (ESI) available: Representative flow cytometry plots of cells incubated with or without cationic CPT/CUR-NPs (1 : 1) for 3 h; Cytotoxicity of blank chitosan-coated NPs and blank HA-functionalized NPs at different concentrations against Colon-26 cells after 48 h of co-incubation. See DOI: 10.1039/c5nr04831a
Curcumin-loaded mixed micelles: preparation, optimization, physicochemical properties and cytotoxicity in vitro.

PubMed

Duan, Yuwei; Wang, Juan; Yang, Xiaoye; Du, Hongliang; Xi, Yanwei; Zhai, Guangxi

2015-01-01

Although curcumin (CUR) can inhibit proliferation and induce apoptosis of tumors, the poor water solubility restricted its clinical application. The aim of this study was to improve the aqueous solubility of CUR and make more favorable changes to bioactivity by preparing curcumin-loaded phospholipid-sodium deoxycholate-mixed micelles (CUR-PC-SDC-MMs). CUR-PC-SDC-MMs were prepared by the thin-film dispersion method. Based on the results of single factor exploration, the preparation technology was optimized using the central composite design-response surface methodology with drug loading and entrapment efficiency (EE%) as indicators. The images of transmission electron microscopy showed that the optimized CUR-PC-SDC-MMs were spherical and well dispersed. The average size of the mixed micelles was 66.5 nm, the zeta potential was about -26.96 mV and critical micelle concentration was 0.0087 g/l. CUR was encapsulated in PC-SDC-MMs with loading capacity of 13.12%, EE% of 87.58%, and the solubility of CUR in water was 3.14 mg/ml. The release results in vitro showed that the mixed micelles presented sustained release behavior compared to the propylene glycol solution of CUR. The IC50 values of CUR-loaded micelles and free drug in human breast carcinoma cell lines were 4.10 μg/ml and 6.93 µg/ml, respectively. It could be concluded from the above results that the CUR-PC-SDC-MMs system might serve as a promising nanocarrier to improve the solubility and bioactivity of CUR.

Identification and characterization of multiple curcumin synthases from the herb Curcuma longa.

PubMed

Katsuyama, Yohei; Kita, Tomoko; Horinouchi, Sueharu

2009-09-03

Curcuminoids are pharmaceutically important compounds isolated from the herb Curcuma longa. Two additional type III polyketide synthases, named CURS2 and CURS3, that are capable of curcuminoid synthesis were identified and characterized. In vitro analysis revealed that CURS2 preferred feruloyl-CoA as a starter substrate and CURS3 preferred both feruloyl-CoA and p-coumaroyl-CoA. These results suggested that CURS2 synthesizes curcumin or demethoxycurcumin and CURS3 synthesizes curcumin, bisdemethoxycurcumin and demethoxycurcumin. The availability of the substrates and the expression levels of the three different enzymes capable of curcuminoid synthesis with different substrate specificities might influence the composition of curcuminoids in the turmeric and in different cultivars.
Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices.

PubMed

Li, Bin; Konecke, Stephanie; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

2013-10-15

Amorphous solid dispersions (ASD) of curcumin (Cur) in cellulose derivative matrices, hydroxypropylmethylcellulose acetate succinate (HPMCAS), carboxymethylcellulose acetate butyrate (CMCAB), and cellulose acetate adipate propionate (CAAdP) were prepared in order to investigate the structure-property relationship and identify polymer properties necessary to effectively increase Cur aqueous solution concentration. XRD results indicated that all investigated solid dispersions were amorphous, even at a 9:1 Cur:polymer ratio. Both stability against crystallization and Cur solution concentration from these ASDs were significantly higher than those from physical mixtures and crystalline Cur. Remarkably, curcumin was also stabilized against chemical degradation in solution. Chemical stabilization was polymer-dependent, with stabilization in CAAdP>CMCAB>HPMCAS>PVP, while matrices enhanced solution concentration as PVP>HPMCAS>CMCAB≈CAAdP. HPMCAS/Cur dispersions have useful combinations of pH-triggered release profile, chemical stabilization, and strong enhancement of Cur solution concentration. Copyright © 2013 Elsevier Ltd. All rights reserved.
Evaluation of an oral carrier system in rats: bioavailability and gastrointestinal absorption properties of curcumin encapsulated PBCA nanoparticles

NASA Astrophysics Data System (ADS)

Sun, Min; Zhao, Lixia; Guo, Chenyu; Cao, Fengliang; Chen, Huanlei; Zhao, Liyan; Tan, Qi; Zhu, Xiuqing; Zhu, Fanping; Ding, Tingting; Zhai, Yingjie; Zhai, Guangxi

2012-02-01

A new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of curcumin (CUR), a poorly soluble drug. The formulation was optimized by orthogonal design and the optimal PBCNs loading CUR exhibited a spherical shape under transmission electron microscopy with a range of 40-400 nm. Physicochemical state of CUR in PBCN was investigated by X-ray diffraction and the possible structure changes occurring in CUR after conjugating with polybutylcyanoacrylate were studied with FTIR. The results indicated that CUR in PBCN was in a non-crystalline state and CUR was encapsulated in PBCN without chemical reaction. The oral pharmacokinetic study was conducted in rats and the relative bioavailability of CUR encapsulated PBCNs to the crude CUR was more than 800%. The in situ absorption experiment in rat intestine indicated the absorption was first order with passive diffusion mechanism. The absorption results in various segments of intestine showed that the main absorption sites were ileum and colon. It can be concluded that PBCNs as an oral carrier can significantly improve the oral absorption of a poorly soluble drug.
Novel star-type methoxy-poly(ethylene glycol) (PEG)-poly(ɛ-caprolactone) (PCL) copolymeric nanoparticles for controlled release of curcumin

NASA Astrophysics Data System (ADS)

Feng, Runliang; Zhu, Wenxia; Song, Zhimei; Zhao, Liyan; Zhai, Guangxi

2013-06-01

To improve curcumin's (CURs) water solubility and release property, a novel star methoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with MPEG, epichlorohydrin, and ɛ-caprolactone as raw materials. The structure of the novel copolymer was characterized by 1H NMR, FT-IR, and GPC. The results of FT-IR and differential scanning calorimeter of CUR-loaded nanoparticles (NPs) prepared by dialysis method showed that CUR was successfully encapsulated into the SMP12 copolymeric NPs with 98.2 % of entrapment efficiency, 10.91 % of drug loading, and 88.4 ± 11.2 nm of mean particle diameter in amorphous forms. The dissolubility of nanoparticulate CUR was increased by 1.38 × 105 times over CUR in water. The obtained blank copolymer showed no hemolysis. A sustained CUR release to a total of approximately 56.13 % was discovered from CUR-NPs in 40 % of ethanol saline solution within 72 h on the use of dialysis method. The release behavior fitted the ambiexponent and biphasic kinetics equation. In conclusion, the copolymeric NPs loading CUR might serve as a potential nanocarrier to improve the solubility and release property of CUR.
The Production of Curli Amyloid Fibers Is Deeply Integrated into the Biology of Escherichia coli

PubMed Central

Smith, Daniel R.; Price, Janet E.; Burby, Peter E.; Blanco, Luz P.; Chamberlain, Justin; Chapman, Matthew R.

2017-01-01

Curli amyloid fibers are the major protein component of the extracellular matrix produced by Enterobacteriaceae during biofilm formation. Curli are required for proper biofilm development and environmental persistence by Escherichia coli. Here, we present a complete and vetted genetic analysis of functional amyloid fiber biogenesis. The Keio collection of single gene deletions was screened on Congo red indicator plates to identify E. coli mutants that had defective amyloid production. We discovered that more than three hundred gene products modulated curli production. These genes were involved in fundamental cellular processes such as regulation, environmental sensing, respiration, metabolism, cell envelope biogenesis, transport, and protein turnover. The alternative sigma factors, σS and σE, had opposing roles in curli production. Mutations that induced the σE or Cpx stress response systems had reduced curli production, while mutant strains with increased σS levels had increased curli production. Mutations in metabolic pathways, including gluconeogenesis and the biosynthesis of lipopolysaccharide (LPS), produced less curli. Regulation of the master biofilm regulator, CsgD, was diverse, and the screen revealed several proteins and small RNAs (sRNA) that regulate csgD messenger RNA (mRNA) levels. Using previously published studies, we found minimal overlap between the genes affecting curli biogenesis and genes known to impact swimming or swarming motility, underlying the distinction between motile and sessile lifestyles. Collectively, the diversity and number of elements required suggest curli production is part of a highly regulated and complex developmental pathway in E. coli. PMID:29088115
Nanoparticle Self-Assembled Grain Like Curcumin Conjugated ZnO: Curcumin Conjugation Enhances Removal of Perylene, Fluoranthene, and Chrysene by ZnO

PubMed Central

Moussawi, Rasha N.; Patra, Digambara

2016-01-01

Curcumin conjugated ZnO, referred as Zn(cur)O, nanostructures have been successfully synthesized, these sub-micro grain-like structures are actually self-assemblies of individual needle-shaped nanoparticles. The nanostructures as synthesized possess the wurtzite hexagonal crystal structure of ZnO and exhibit very good crystalline quality. FT-Raman and TGA analysis establish that Zn(cur)O is different from curcumin anchored ZnO (ZnO@cur), which is prepared by physically adsorbing curcumin on ZnO surfaces. Chemically Zn(cur)O is more stable than ZnO@cur. Diffuse reflectance spectroscopy indicates Zn(cur)O have more impurities compared to ZnO@cur. The solid-state photoluminescence of Zn(cur)O has been investigated, which demonstrates that increase of curcumin concentration in Zn(cur)O suppresses visible emission of ZnO prepared through the same method, this implies filling ZnO defects by curcumin. However, at excitation wavelength 425 nm the emission is dominated by fluorescence from curcumin. The study reveals that Zn(cur)O can remove to a far extent high concentrations of perylene, fluoranthene, and chrysene faster than ZnO. The removal depends on the extent of curcumin conjugation and is found to be faster for PAHs having smaller number of aromatic rings, particularly, it is exceptional for fluoranthene with 93% removal after 10 minutes in the present conditions. The high rate of removal is related to photo-degradation and a mechanism has been proposed. PMID:27080002
Real-time optotracing of curli and cellulose in live Salmonella biofilms using luminescent oligothiophenes.

PubMed

Choong, Ferdinand X; Bäck, Marcus; Fahlén, Sara; Johansson, Leif Bg; Melican, Keira; Rhen, Mikael; Nilsson, K Peter R; Richter-Dahlfors, Agneta

2016-01-01

Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research.
Real-time optotracing of curli and cellulose in live Salmonella biofilms using luminescent oligothiophenes

PubMed Central

Choong, Ferdinand X; Bäck, Marcus; Fahlén, Sara; Johansson, Leif BG; Melican, Keira; Rhen, Mikael; Nilsson, K Peter R; Richter-Dahlfors, Agneta

2016-01-01

Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research. PMID:28721253
Antifungal curcumin promotes chitin accumulation associated with decreased virulence of Sporothrix schenckii.

PubMed

Huang, Lilin; Zhang, Jing; Song, Tianzhang; Yuan, Liyan; Zhou, Junjie; Yin, Hongling; He, Tailong; Gao, Wenchao; Sun, Yao; Hu, Xuchu; Huang, Huaiqiu

2016-05-01

Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR-treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice. Copyright © 2016 Elsevier B.V. All rights reserved.
Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin

PubMed Central

Li, Chong; Zhang, Yan; Su, Tingting; Feng, Lianlian; Long, Yingying; Chen, Zhangbao

2012-01-01

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability. PMID:23233804
Silica-coated flexible liposomes as a nanohybrid delivery system for enhanced oral bioavailability of curcumin.

PubMed

Li, Chong; Zhang, Yan; Su, Tingting; Feng, Lianlian; Long, Yingying; Chen, Zhangbao

2012-01-01

We investigated flexible liposomes as a potential oral drug delivery system. However, enhanced membrane fluidity and structural deformability may necessitate liposomal surface modification when facing the harsh environment of the gastrointestinal tract. In the present study, silica-coated flexible liposomes loaded with curcumin (CUR-SLs) having poor water solubility as a model drug were prepared by a thin-film method with homogenization, followed by the formation of a silica shell by the sol-gel process. We systematically investigated the physical properties, drug release behavior, pharmacodynamics, and bioavailability of CUR-SLs. CUR-SLs had a mean diameter of 157 nm and a polydispersity index of 0.14, while the apparent entrapment efficiency was 90.62%. Compared with curcumin-loaded flexible liposomes (CUR-FLs) without silica-coatings, CUR-SLs had significantly higher stability against artificial gastric fluid and showed more sustained drug release in artificial intestinal fluid as determined by in vitro release assays. The bioavailability of CUR-SLs and CUR-FLs was 7.76- and 2.35-fold higher, respectively, than that of curcumin suspensions. Silica coating markedly improved the stability of flexible liposomes, and CUR-SLs exhibited a 3.31-fold increase in bioavailability compared with CUR-FLs, indicating that silica-coated flexible liposomes may be employed as a potential carrier to deliver drugs with poor water solubility via the oral route with improved bioavailability.
Cellulose modulates biofilm formation by counteracting curli-mediated colonization of solid surfaces in Escherichia coli.

PubMed

Gualdi, Luciana; Tagliabue, Letizia; Bertagnoli, Stefano; Ieranò, Teresa; De Castro, Cristina; Landini, Paolo

2008-07-01

In enterobacteria, the CsgD protein activates production of two extracellular structures: thin aggregative fimbriae (curli) and cellulose. While curli fibres promote biofilm formation and cell aggregation, the evidence for a direct role of cellulose as an additional determinant for biofilm formation is not as straightforward. The MG1655 laboratory strain of Escherichia coli only produces limited amounts of curli and cellulose; however, ectopic csgD expression results in strong stimulation of curli and cellulose production. We show that, in a csgD-overexpressing derivative of MG1655, cellulose production negatively affects curli-mediated surface adhesion and cell aggregation, thus acting as a negative determinant for biofilm formation. Consistent with this observation, deletion of the bcsA gene, necessary for cellulose production, resulted in a significant increase in curli-dependent adhesion. We found that cellulose production increased tolerance to desiccation, suggesting that the function of cellulose might be related to resistance to environmental stresses rather than to biofilm formation. Production of the curli/cellulose network in enterobacteria typically takes place at low growth temperature (<32 degrees C), but not at 37 degrees C. We show that CsgD overexpression can overcome temperature-dependent control of the curli-encoding csgBA operon, but not of the cellulose-related adrA gene, suggesting very tight temperature control of cellulose production in E. coli MG1655.
RcsB contributes to the distinct stress fitness between Escherichia coli O157:H7 curli variants of 1993 hamburger-associated outbreak strains

USDA-ARS?s Scientific Manuscript database

Curli are adhesive fimbriae of Enterobactericaeae and are involved in surface attachment, cell aggregation and biofilm formation. We previously reported that natural curli variants of E. coli O157:H7 (EcO157) displayed distinct acid resistance; however, this difference was not linked to the curli fi...
Effect of curtovirus species competitiveness in host plants on transmission and incidence of Beet severe curly top virus and Beet mild curly top virus

USDA-ARS?s Scientific Manuscript database

Curly top disease, caused by viruses in the genus Curtovirus, causes significant economic losses for sugarbeet and other crops throughout the western United States. Recent studies demonstrated the two most abundant curtovirus species in the US are Beet severe curly top virus (BSCTV) and Beet mild c...
Interaction between curcumin and human serum albumin in the presence of excipients and the effect of binding on curcumin photostability.

PubMed

Vukićević, Milica; Tønnesen, Hanne Hjorth

2016-01-01

Curcumin (Cur) is known to bind to human serum albumin (HSA) which may lead to a reduced phototoxic effect of the compound in the presence of serum or saliva. The influence of excipients on the Cur-HSA binding was studied by HSA florescence quenching and Cur absorption and emission spectroscopy in the presence and absence of the selected excipients. Photostabilty of Cur in the presence of HSA was evaluated, as well as the effect of excipients on HSA bound Cur photodegradation. Cyclodextrins (CDs) (2-hydroxypropyl-β-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin) and polymers (polyethylene glycol 400, PEG 400 and Pluronic F-127, PF-127) were selected for the study. CDs and PF-127 seem to decrease Cur binding to HSA, probably through competitive binding. Cur was still bound to HSA in polyethylene glycol (PEG) solutions at the highest investigated concentration (5% w/v). However, high PEG concentration appears to have effect on the protein conformation, as shown by the fluorescence quenching study. Low Cur photostability in the presence of HSA could be improved by the addition of hydroxylpropyl-γ-cyclodextrin (HPγCD) to the samples, whereas PEG and PF-127 showed no effect.
Collagen-cellulose nanocrystal scaffolds containing curcumin-loaded microspheres on infected full-thickness burns repair.

PubMed

Guo, Rui; Lan, Yong; Xue, Wei; Cheng, Biao; Zhang, Yuanming; Wang, Changyong; Ramakrishna, Seeram

2017-12-01

Burn infection is a serious problem that delays wound healing and leads to death. Curcumin (Cur) has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activity. However, its instability, extremely low aqueous solubility and bioavailability in physiological fluids may make it difficult to maintain local Cur concentrations above the minimum inhibitory concentration for burn infection treatment. The objective of this study was to construct complexes of Cur/gelatin microspheres (GMs) and porous collagen (Coll)-cellulose nanocrystals (CNCs) composite scaffolds for full-thickness burn infection treatment. The Cur/GMs/Coll-CNCs scaffolds had high porosity, available pore size, and a long and sustained Cur release profile. Furthermore, the composite scaffold exhibited remarkably strong antibacterial activity. Hence, we evaluated the wound-healing effects and antibacterial properties of Cur/GMs/Coll-CNCs scaffolds in a rat full-thickness burn infection model. The Cur/GMs/Coll-CNCs scaffold was able to prevent not only local inflammation but also accelerated dermis regeneration. Thus, we conclude that Cur/GMs/Coll-CNCs scaffolds can act as an effective dermal regeneration template for full-thickness burn wound infection healing in rats models. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Solubility profiles, hydration and desolvation of curcumin complexed with γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin

NASA Astrophysics Data System (ADS)

Shityakov, Sergey; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Roewer, Norbert; Förster, Carola; Broscheit, Jens

2017-04-01

In this study, we investigated curcumin (CUR) solubility profiles and hydration/desolvation effects of this substance formulated with γ-cyclodextrin (γ-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) excipients. The CUR/HP-γ-CD complex was found to be more stable in solution with the highest apparent stability constant for CUR/HP-γ-CD (Kc = 1.58*104 M-1) as the more soluble form in distilled water. The in silico calculations, including molecular docking, Monte Carlo (MC), and molecular dynamics (MD) simulations, indicated that water molecules play an important role in host-guest complexation mediating the CUR binding to cyclodextrins via hydrogen bond formations. The CUR hydration/desolvation effects contributed to the complex formation by elevating the CUR binding affinity to both CDs. The CUR/HP-γ-CD complex after the CUR hydration was determined with a minimal Gibbs free energy of binding (ΔGbind = -9.93 kcal*mol-1) due to the major hydrophobic (vdW) forces. Overall, the results of this study can aid a development of cyclodextrin-based drug delivery vectors, signifying the importance of water molecules during the formulation processes.
Enhancement of Oral Bioavailability of Curcumin by a Novel Solid Dispersion System.

PubMed

Hu, Liandong; Shi, Yanjing; Li, Jian Heng; Gao, Na; Ji, Jing; Niu, Feng; Chen, Queting; Yang, Xiaoning; Wang, Shaocheng

2015-12-01

The objective of this study was to improve the solubility and bioavailability of curcumin by a new curcumin dripping pills (Cur-DPs) formulation using melt mixing methods. The optimal formulation consisted of Polyethoxylated 40 hydrogenated castor oil (Cremophor RH40), Poloxamer 188, and Polyethylene glycol 4000 (PEG 4000). Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) were used to verify the forming of Cur-DPs. All the physical characterization information proved the formation of Cur-DPs, and the results demonstrated the superiority of the dripping pills in dissolution rates. The pharmacokinetic study of Cur-DPs was performed in rats compared to the pure curcumin suspension. The oral bioavailability of poorly water-soluble curcumin was successfully improved by CUR-DPs. And the stability of prepared Cur-DP was also in a good state in 3 months. These results identified the Cur-DPs was an effective new approach for pharmaceutical application.
Construction and characterization of curcumin nanoparticles system

NASA Astrophysics Data System (ADS)

Sun, Weitong; Zou, Yu; Guo, Yaping; Wang, Lu; Xiao, Xue; Sun, Rui; Zhao, Kun

2014-03-01

This study was aimed at developing a nanoparticles system for curcumin, a widely used traditional Chinese medicine, but with the disadvantage of poor aqueous solubility. The objective was intended to improve in vitro release characteristics, enhance blood and gastrointestinal stability, increase bioavailability and pharmacological activities. Curcumin nanoparticles system (Cur-NS) was prepared by ionotropic gelation technique. Cur-NS was characterized by particle size, zeta potential, drug entrapment efficiency, drug loading, and physical stability, respectively. Cur-NS presented controlled release properties, and the release properties of Cur from NS were fit non-Fickian mechanism, controlled by the expected diffusional release and the erosion or solubilization from the crosslink layer of polymer carrier. In addition, the pharmacokinetic study in rats revealed a notable improved oral bioavailability of Cur, and the anti-tumor activity in vivo of Cur-NS on tumor growth was investigated. Cur-NS significantly inhibited tumor effect compared with non-vehicle group, thus making it a potential candidate for cancer therapy.
Nucleation and growth of a bacterial functional amyloid at single fiber resolution

PubMed Central

Feuillie, Cécile; Jonckheere, Wim; Valotteau, Claire; Dufrêne, Yves F.; Remaut, Han

2017-01-01

Curli are functional amyloids produced by proteobacteria like Escherichia coli, as part of the extracellular matrix that holds cells together into biofilms. The molecular events during curli nucleation and fiber extension remain largely unknown. Combining observations from curli amyloidogenesis in bulk solutions with real-time in situ nanoscopic imaging at the single fiber level, we show that curli display polar growth, and detect two kinetic regimes of fiber elongation. Single fibers exhibit stop-and-go dynamics characterized by bursts of steady-state growth alternated with periods of stagnation. At high subunit concentrations fibers show constant, unperturbed burst growth. Curli follow a one-step nucleation process, where monomers contemporaneously fold and oligomerize into minimal fiber units that have growth characteristics identical to the mature fibrils. Kinetic data and interaction studies of curli fibrillation in the presence of the natural inhibitor CsgC show the inhibitor binds curli fibers and predominantly acts at the level of fiber elongation. PMID:28628096

Transient spectra study on photo-dynamics of curcumin

NASA Astrophysics Data System (ADS)

Qian, Tingting; Wang, Mei; Wang, Jiao; Zhu, Rongrong; He, Xiaolie; Sun, Xiaoyu; Sun, Dongmei; Wang, Qingxiu; Wang, ShiLong

2016-09-01

A novel mechanism of DNA damage induced by photosensitized curcumin (Cur) was explored using laser flash photolysis, pulse radiolysis and gel electrophoresis. Cur neutral radical (Currad) was confirmed as an identical product in photo-sensitization of Cur by laser flash photolysis and pulse radiolysis. A series of reaction rate constants between Currad and nucleic acid bases/nucleotides were determined by pulse radiolysis. Gel electrophoresis was carried out to investigate damage induced by photosensitized Cur to biologically active DNA. The results indicate that the damage to DNA may be caused by Currad produced from the photosensitization of Cur.
Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq.

PubMed

Guo, Yue; Su, Zheng-Yuan; Zhang, Chengyue; Gaspar, John M; Wang, Rui; Hart, Ronald P; Verzi, Michael P; Kong, Ah-Ng Tony

2017-07-01

Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA+1% CUR were given to mice from 1week prior to the AOM injection until the experiment was terminated 22weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR. Copyright © 2017 Elsevier Inc. All rights reserved.
Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

PubMed

Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

2018-05-03

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Trastuzumab- and Fab' fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo.

PubMed

Duan, Dongyu; Wang, Aiping; Ni, Ling; Zhang, Liping; Yan, Xiuju; Jiang, Ying; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

2018-01-01

Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab' (antigen-binding fragments cut from TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs. Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.
Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue.

PubMed

Zhang, Xuemei; Li, Xuejuan; Hua, Hongchen; Wang, Aiping; Liu, Wanhui; Li, Youxin; Fu, Fenghua; Shi, Yanan; Sun, Kaoxiang

2017-01-01

Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs). The cyclic hexapeptide c(RGDf(N-me) VK)-C (cHP) has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly(d,l-lactide-co-glycolide) (PEG-PLGA) conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs) was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells. The targeted cHP/Cur-NPs, c(RGDf(N-me)VK)-C-modified Cur-NPs, exhibited improved binding, uptake, and penetration abilities than non-targeting NPs for glioma cells, cell spheres, and glioma tissue. In conclusion, c(RGDf(N-me)VK)-C can serve as an effective targeting ligand, and cHP/Cur-NPs can be exploited as a potential drug delivery system for targeting gliomas.
Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage.

PubMed

Hassani, S; Sepand, M R; Jafari, A; Jaafari, J; Rezaee, R; Zeinali, M; Tavakoli, F; Razavi-Azarkhiavi, K

2015-06-01

There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues. © The Author(s) 2014.
Nanotechnology-based treatment for chemotherapy-resistant breast cancer

NASA Astrophysics Data System (ADS)

Abouzeid, Abraham H.; Patel, Niravkumar R.; Rachman, Ilya M.; Senn, Sean; Torchilin, Vladimir P.

2014-08-01

Background: Treatment of metastatic cancer remains a formidable clinical challenge. Better therapeutic options with improved tissue penetration and tumor cell uptake are urgently needed. Targeted nanotherapy, for improved delivery, and combinatory drug administration aimed at inhibiting chemo-resistance may be the solution. Purpose: The study was performed to evaluate the therapeutic efficacy of polymeric PEG-PE micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against MDA-MB-231 human breast adenocarcinoma cells both in vitro and in vivo. Methods: MDA-MB-231 DOX-resistant cells were treated with non-targeted and GLUT1-targeted CUR and DOX micelles as a single agent or in combination. Tumor cells were also inoculated in female nude mice. Established tumors were treated with the micellar formulations at a dose of 6 mg/kg CUR and 1 mg/kg DOX every 2 d for a total of 7 injections. Results: CUR+DOX-loaded micelles decorated with GLUT1 had a robust killing effect even at low doses of DOX in vitro. At the doses chosen, non-targeted CUR and CUR+DOX micelles did not exhibit significant tumor inhibition versus control. However, GLUT1-CUR and GLUT1-CUR+DOX micelles showed a significant tumor inhibition effect with an improvement in survival. Conclusion: We showed a dramatic improvement in efficacy between the non-targeted and GLUT1-targeted formulations both in vitro and in vivo. Also, importantly, the addition of CUR to the micelle, has restored sensitivity to DOX, with resultant tumor growth inhibition. Hence, we confirmed that GLUT1-CUR+DOX micelles are effective in vitro and in vivo and deserve further investigation.
Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue

PubMed Central

Zhang, Xuemei; Li, Xuejuan; Hua, Hongchen; Wang, Aiping; Liu, Wanhui; Li, Youxin; Fu, Fenghua; Shi, Yanan; Sun, Kaoxiang

2017-01-01

Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs). The cyclic hexapeptide c(RGDf(N-me) VK)-C (cHP) has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly(d,l-lactide-co-glycolide) (PEG-PLGA) conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs) was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells. The targeted cHP/Cur-NPs, c(RGDf(N-me)VK)-C-modified Cur-NPs, exhibited improved binding, uptake, and penetration abilities than non-targeting NPs for glioma cells, cell spheres, and glioma tissue. In conclusion, c(RGDf(N-me)VK)-C can serve as an effective targeting ligand, and cHP/Cur-NPs can be exploited as a potential drug delivery system for targeting gliomas. PMID:28848349
Synergistic role of curli and cellulose in cell adherence and biofilm formation of attaching and effacing Escherichia coli and identification of Fis as a negative regulator of curli.

PubMed

Saldaña, Zeus; Xicohtencatl-Cortes, Juan; Avelino, Fabiola; Phillips, Alan D; Kaper, James B; Puente, José L; Girón, Jorge A

2009-04-01

Curli are adhesive fimbriae of Escherichia coli and Salmonella enterica. Expression of curli (csgA) and cellulose (bcsA) is co-activated by the transcriptional activator CsgD. In this study, we investigated the contribution of curli and cellulose to the adhesive properties of enterohaemorragic (EHEC) O157:H7 and enteropathogenic E. coli (EPEC) O127:H6. While single mutations in csgA, csgD or bcsA in EPEC and EHEC had no dramatic effect on cell adherence, double csgAbcsA mutants were significantly less adherent than the single mutants or wild-type strains to human colonic HT-29 epithelial cells or to cow colon tissue in vitro. Overexpression of csgD (carried on plasmid pCP994) in a csgD mutant, but not in the single csgA or bscA mutants, led to significant increase in adherence and biofilm formation in EPEC and EHEC, suggesting that synchronized over-production of curli and cellulose enhances bacterial adherence. In line with this finding, csgD transcription was activated significantly in the presence of cultured epithelial cells as compared with growth in tissue culture medium. Analysis of the influence of virulence and global regulators in the production of curli in EPEC identified Fis (factor for inversion stimulation) as a, heretofore unrecognized, negative transcriptional regulator of csgA expression. An EPEC E2348/69Deltafis produced abundant amounts of curli whereas a double fis/csgD mutant yielded no detectable curli production. Our data suggest that curli and cellulose act in concert to favour host colonization, biofilm formation and survival in different environments.
Synthesis, characterization and in vitro/in vivo evaluation of novel reduction-sensitive hybrid nano-echinus-like nanomedicine.

PubMed

Wang, Kaili; Guo, Chunjing; Zou, Shaohua; Yu, Yueming; Fan, Xinxin; Wang, Bingjie; Liu, Mengna; Fang, Lei; Chen, Daquan

2018-04-27

To remedy the problems resulting from the usage of anti-cancer drugs in cancer chemotherapy, such as deficient drug concentration in tumour cells, low water-solubility and non-specific distribution of antitumour drugs, a kind of reduction-sensitive polymer prodrug of curcumin (Cur) containing in the nano-echinus was synthesized and designed. The nano-echinus-like nanomedicine presented synergistic effect with glycyrrhetic acid (GA) and oligomeric hyaluronic (HA) for targeting and combating HepG2 human liver cancer cell. Firstly, a kind of small molecular prodrug of Cur, dithiodipropionic acid-Cur (-SS-Cur), was chemically conjugated onto the side chain of the conjugated glycyrrhetic acid- oligomeric hyaluronic (GA-HA) to generate an amphiphilic polymeric prodrug of Cur, GA-HA-SS-Cur. The obtained GA-HA-SS-Cur prodrug and subsidiary material mPEG-DSPE could self-assemble into a sea urchin-like micelles in aqueous media and release Cur rapidly in response to glutathion (GSH). Then, Cur was loaded into the nano-echinus with a particle size of (118.1 ± 0.2 nm) and drug-loading efficiency of (8.03 ± 2.1%). The structure of GA-HA-SS-Cur was characterized by 1 H-NMR in this report. The morphology of micelles was observed with a transmission electron microscope (TEM). Subsequently, the reduction-sensitivity of the nano-echinus was confirmed by the changes in in-vitro drug release after different concentrations of GSH treatment. Besides, the cellular uptake behaviour and MTT assays of the nano-echinus were investigated, suggesting that the nano-echinus was of desirable safety and could be taken into HepG2 cells in a time-dependent manner. Later, anti-tumour efficacy in vivo revealed the effective inhibition of tumour growth.
The comprehensive electrophysiological study of curcuminoids on delayed-rectifier K+ currents in insulin-secreting cells.

PubMed

Kuo, Ping-Chung; Yang, Chia-Jung; Lee, Yu-Chi; Chen, Pei-Chun; Liu, Yen-Chin; Wu, Sheng-Nan

2018-01-15

Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique. CUR suppressed the amplitude of delayed-rectifier K + current (I K(DR) ) in a time-, state- and concentration-dependent manner in these cells and the inhibition was not reversed by diazoxide, nicorandil or chlorotoxin. The value of dissociation constant for CUR-induced suppression of I K(DR) in INS-1 cells was 1.26μM. Despite the inability of CUR to alter the activation rate of I K(DR) , it accelerated current inactivation elicited by membrane depolarization. Increasing CUR concentrations shifted the inactivation curve of I K(DR) to hyperpolarized potential and slowed the recovery of I K(DR) inactivation. CUR, DMC, and BDMC all exerted depressant actions on I K(DR) amplitude to a similar magnitude, although DMC and BDMC did not increase current inactivation clearly. CUR slightly suppressed the peak amplitude of voltage-gated Na + current. CUR, DMC and BDMC depolarized the resting potential and increased firing frequency of action potentials. The CUR-mediated decrease of I K(DR) and the increase of current inactivation also occurred in βTC-6 INS-1 cells. Taken these results together, these effects may be one of the possible mechanisms contributing their insulin-releasing effect. Copyright © 2017 Elsevier B.V. All rights reserved.
Cytotoxicity of curcumin silica nanoparticle complexes conjugated with hyaluronic acid on colon cancer cells.

PubMed

Singh, Surya Prakash; Sharma, Mrinalini; Gupta, Pradeep Kumar

2015-03-01

We report results of our investigations on the cytotoxic efficacy of Organically modified silica nanoparticle (SiNp)-curcumin complex conjugated with hyaluronic acid (HA) (HA-SiNp-cur) and HA free SiNp-cur complex in human colon carcinoma (colo-205) cells. Curcumin was loaded in SiNp and resulting complexes were conjugated with HA, which has a strong affinity for cancer cells expressing CD44. After conjugation with HA, the average size of the SiNp-cur nanoparticles increased from 45 nm to 70 nm, and zeta potential changed to -33 mV from -26 mV. Compared to free curcumin and SiNp-cur, curcumin in HA-SiNp was more stable. The uptake and cytotoxicity of curcumin delivered through HA-SiNp-cur was significantly higher in monolayer and spheroids as compared to free curcumin and HA free SiNp-cur. Concomitantly, HA-SiNp-cur complex treatment resulted in higher inhibition of growth and migration of cells in spheroids. Further, incubation of colo-205 cancer cells with an excess of HA impaired the uptake of HA-SiNp-cur confirming the involvement of receptor mediated endocytosis in the uptake of HA conjugated nanocomplex. Time dependent increase in the fluorescence of curcumin observed in the release media when HA-SiNp-cur was incubated with hyaluronidase suggests involvement of enzyme in release of curcumin from nanoparticle. Copyright © 2014 Elsevier B.V. All rights reserved.
Curcumin-polymeric nanoparticles against colon-26 tumor-bearing mice: cytotoxicity, pharmacokinetic and anticancer efficacy studies.

PubMed

Chaurasia, Sundeep; Chaubey, Pramila; Patel, Ravi R; Kumar, Nagendra; Mishra, Brahmeshwar

2016-01-01

Curcumin (CUR), can inhibit proliferation and induce apoptosis of tumor cells, its extreme insolubility and limited bioavailability restricted its clinical application. An innovative polymeric nanoparticle of CUR has been developed to enhance the bioavailability and anti-cancer efficacy of CUR, in vitro and in vivo. Cationic copolymer Eudragit E 100 was selected as carrier, which can enhance properties of poor bioavailable chemotherapeutic drugs (CUR). The CUR-loaded Eudragit E 100 nanoparticles (CENPs) were prepared by emulsification-diffusion-evaporation method. The in vitro cytotoxicity study of CENPs was carried out using sulphorhodamine B assay. Pharmacokinetic and anti-cancer efficacy of CENPs was investigated in Wister rats as well as colon-26 tumor-bearing mice after oral administration. CENPs showed acceptable particle size and percent entrapment efficiency. In vitro cytotoxicity studies in terms of 50% cell growth inhibition values demonstrated ∼19-fold reduction when treated with CENPs as compared to pure CUR. ∼91-fold increase in Cmax and ∼95-fold increase in AUC0-12h were observed indicating a significant enhancement in the oral bioavailability of CUR when orally administered as CENPs compared to pure CUR. The in vivo anti-cancer study performed with CENPs showed a significant increase in efficacy compared with pure CUR, as observed by tumor volume, body weight and survival rate. The results clearly indicate that the developed polymeric nanoparticles offer a great potential to improve bioavailability and anticancer efficacy of hydrophobic chemotherapeutic drug.
Developing and Evaluating In Vitro Effect of Poly(Ethylene Glycol) Conjugated Curcumin on Human Cancer Cell Lines.

PubMed

Tung, Bui Thanh; Hai, Nguyen Thanh; Son, Phan Ke

2016-01-01

Curcumin has been shown to possess strong cytotoxic effect against various cancer cell lines. However, curcumin has not applied as a drug for treatment of cancer yet due to low solubility in water and low bioavailability. The aims of this study were to prepare a new polyethylene glycol (PEG) conjugated curcumin and to evaluate its antitumor activity in vitro. PEG-CUR was prepared by the reaction between curcumin and PEG. PEG-CUR which was characterized by SEM, TEM, FTIR, DSC and 1H NMR analysis. The physicochemical parameters of PEG-CUR such as zeta potential, size distribution, solubility and percentage of curcumin were also investigated. Our results showed that the percentage of curcumin in PEG-CUR was 13.26 ± 1.25 %. PEG-CUR has nanosize values of 96.3 nm and the zeta potential values of - 48.4 mV. The PEG-CUR showed significantly increasing curcumin's solubility in water and another medium such as in 0,1 N HCl, phosphate buffer pH 4.5 and pH 6.8 solution and n-octanol. Our data also have shown cytotoxicity effect of PEG-CUR was much greater than curcumin-free in two different HepG2 and HCT116 cancer cell lines. It could be concluded from our results that the PEG-CUR may be a potential candidate for cancer treatment. Further studies are needed to evaluate the antitumor efficacy of PEG-CUR in vivo.
Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.

PubMed

Zhao, Yinbo; Lin, Dayong; Wu, Fengbo; Guo, Li; He, Gu; Ouyang, Liang; Song, Xiangrong; Huang, Wei; Li, Xiang

2014-09-29

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg-Gly-Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD-lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))-mPEG (methoxyl poly(ethylene- glycol)), RGD-polyethylene glycol (PEG)-cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD-lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD-lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD-lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD-lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD-lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD-lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD-lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.
Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: current state-of-the-art.

PubMed

Ahmad, Mohammad Zaki; Alkahtani, Saad Ahmed; Akhter, Sohail; Ahmad, Farhan Jalees; Ahmad, Javed; Akhtar, Mohammad Shabib; Mohsin, Nehal; Abdel-Wahab, Basel A

2016-01-01

Comprehensive pharmacological screening of curcumin (CUR) has given the evidence that it is an excellent naturally occurring therapeutic moiety for cancer. It is very well tolerated with insignificant toxicity even after high doses of oral administration. Irrespective of its better quality as an anticancer agent, therapeutic application of CUR is hampered by its extremely low-aqueous solubility and poor bioavailability, rapid clearance and low-cellular uptake. A simple means of breaking up the restrictive factor of CUR is to perk-up its aqueous solubility, improve its bioavailability, protect it from degradation, and metabolism and potentiate its targeting capacity towards the cancer cell. The development in the field of nanomedicine has made excellent progresses toward enhancing the bioavailability of lipophilic drugs like CUR. Nanoparticles (NPs) are capable to deliver the CUR at specific area and thereby prevent it from physiological degradation and systemic clearance. In recent year, an assortment of nanomedicine-based novel drug delivery system has been designed to potentiate the bioavailability of CUR towards anticancer therapy. In this review, we discuss the recent development in the field of nanoCUR (NanoCur), including polymeric micelles, liposome, polymeric NPs, nanoemulsion, nanosuspension, solid lipid NPs (SLNPs), polymer conjugates, nanogel, etc. in anticancer application.
Effects of manure-application practices on curli production by Escherichia coli transported through soil

NASA Astrophysics Data System (ADS)

Truhlar, A. M.; Salvucci, A. E.; Siler, J. D.; Richards, B. K.; Geohring, L.; Walter, M. T.; Hay, A. G.

2014-12-01

The release of Escherichia coli into the environment from untreated manure can pose a threat to human health. Environmental survival of E. coli has been linked to extracellular fibers called curli. We investigated the effect of manure management (surface application followed by incorporation versus immediate incorporation) on the relative abundance of curli-producing E. coli in subsurface drainage effluent. Samples were collected from three dairy farms. The proportion of curli-producing E. coli in the manure storage facilities was uniform across the farms. However, the abundance of curli-producing E. coli was much greater (P < 0.05) in the tile drains of farms performing surface application of manure than in the tile drain of the farm that incorporated manure. This field result was corroborated by controlled soil column experiments; the abundance of curli-producing E. coli in soil column effluents was greater (P < 0.05) when manure was surface-applied than when it was incorporated. Our findings suggest selection pressures resulting from the different manure application methods affected curli production by E. coli isolates transported through soil. Given the importance of curli production in pathogenesis, this work highlights the effect that manure management strategies may have on pathogenesis-associated phenotypes of bacteria in agricultural subsurface runoff.
Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

PubMed Central

Lin, Jianwen; Zheng, Zhenyang; Shi, Xiaolei; Di, Wei; Qi, Weiwei; Zhu, Yingting; Zhou, Guijuan; Fang, Yannan

2014-01-01

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1. PMID:24983737
Enhanced oral bioavailability and antiasthmatic efficacy of curcumin using redispersible dry emulsion.

PubMed

Jang, Dong-Jin; Kim, Sung Tae; Oh, Euichaul; Lee, Kooyeon

2014-01-01

Dry emulsion containing curcumin (DE-CUR) was prepared for oral delivery of poorly water-soluble curcumin, and its oral bioavailability and antiasthmatic efficacy was evaluated. After comparison of the solubility of curcumin in various oils, Plurol® Oleique CC497 was selected to be the oil phase due to its higher solubility of CUR than other oils. A dry emulsion prepared by spray-drying of a homogenized oil-in-water emulsion was well-reconstituted in water, fabricating similar particle distribution and in vitro release to that of a dispersed homogeneous emulsion before spraying. The release of DE-CUR was much higher than that of curcumin (85.3 vs. 1.7% release at 60 min). Consequently, DE-CUR resulted in 12.0- and 7.1-fold higher Cmax and AUC0-24h than curcumin. In a murine asthma model, DE-CUR effectively suppressed airway hyperresponsiveness and levels of T-helper cytokines such as interleukin-4, inteleukin-5, and interleukin-13. These findings demonstrate that the DE-CUR shows a potential for the development of functional foods or medicines including CUR.
A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

PubMed Central

Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

2017-01-01

Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy. PMID:28281678

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers.

PubMed

Wang, Fengling; Chen, Jin; Dai, Wenting; He, Zhengmin; Zhai, Dandan; Chen, Weidong

2017-09-01

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L-1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.
A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

NASA Astrophysics Data System (ADS)

Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

2017-03-01

Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.
Modulating bacterial and gut mucosal interactions with engineered biofilm matrix proteins.

PubMed

Duraj-Thatte, Anna M; Praveschotinunt, Pichet; Nash, Trevor R; Ward, Frederick R; Joshi, Neel S

2018-02-22

Extracellular appendages play a significant role in mediating communication between bacteria and their host. Curli fibers are a class of bacterial fimbria that is highly amenable to engineering. We demonstrate the use of engineered curli fibers to rationally program interactions between bacteria and components of the mucosal epithelium. Commensal E. coli strains were engineered to produce recombinant curli fibers fused to the trefoil family of human cytokines. Biofilms formed from these strains bound more mucins than those producing wild-type curli fibers, and modulated mucin rheology as well. When treated with bacteria producing the curli-trefoil fusions mammalian cells behaved identically in terms of their migration behavior as when they were treated with the corresponding soluble trefoil factors. Overall, this demonstrates the potential utility of curli fibers as a scaffold for the display of bioactive domains and an untapped approach to rationally modulating host-microbe interactions using bacterial matrix proteins.
The Functional Curli Amyloid Is Not Based on In-register Parallel β-Sheet Structure*

PubMed Central

Shewmaker, Frank; McGlinchey, Ryan P.; Thurber, Kent R.; McPhie, Peter; Dyda, Fred; Tycko, Robert; Wickner, Reed B.

2009-01-01

The extracellular curli proteins of Enterobacteriaceae form fibrous structures that are involved in biofilm formation and adhesion to host cells. These curli fibrils are considered a functional amyloid because they are not a consequence of misfolding, but they have many of the properties of protein amyloid. We confirm that fibrils formed by CsgA and CsgB, the primary curli proteins of Escherichia coli, possess many of the hallmarks typical of amyloid. Moreover we demonstrate that curli fibrils possess the cross-β structure that distinguishes protein amyloid. However, solid state NMR experiments indicate that curli structure is not based on an in-register parallel β-sheet architecture, which is common to many human disease-associated amyloids and the yeast prion amyloids. Solid state NMR and electron microscopy data are consistent with a β-helix-like structure but are not sufficient to establish such a structure definitively. PMID:19574225
Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

PubMed

Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

2016-05-06

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.
Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability.

PubMed

Parikh, Ankit; Kathawala, Krishna; Song, Yunmei; Zhou, Xin-Fu; Garg, Sanjay

2018-05-29

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.
Comparative Neuroprotective Effects of Dietary Curcumin and Solid Lipid Curcumin Particles in Cultured Mouse Neuroblastoma Cells after Exposure to Aβ42

PubMed Central

2017-01-01

Aggregation of amyloid beta protein (Aβ) and phosphorylated tau (p-Tau) plays critical roles in pathogenesis of Alzheimer's disease (AD). As an antiamyloid natural polyphenol, curcumin (Cur) has a potential role in prevention of neurodegeneration in AD. However, due to limited absorption of the dietary Cur, the solid lipid Cur particles (SLCP) have been suggested as being more effective for AD therapy. In the present study, we compared the role of dietary Cur and SLCP on oxidative stress, neuronal death, p-Tau level, and certain cell survival markers in vitro, after exposure to Aβ42. Mouse neuroblastoma cells were exposed to Aβ42 for 24 h and incubated with or without dietary Cur and/or SLCP. Reactive oxygen species (ROS), apoptotic cell death, p-Tau, and tau kinase (including GSK-3β and cell survival markers, such as total Akt, phosphorylated Akt, and PSD95 levels) were investigated. SLCP showed greater permeability than dietary Cur in vitro, decreased ROS production, and prevented apoptotic death. In addition, SLCP also inhibited p-Tau formation and significantly decreased GSK-3β levels. Further, the cell survival markers, such as total Akt, p-Akt, and PSD95 levels, were more effectively maintained by SLCP than dietary Cur in Aβ42 exposed cells. Therefore, SLCP may provide greater neuroprotection than dietary Cur in Alzheimer's disease. PMID:28567323
Characteristics and cytotoxicity of folate-modified curcumin-loaded PLA-PEG micellar nano systems with various PLA:PEG ratios.

PubMed

Phan, Quoc Thong; Le, Mai Huong; Le, Thi Thu Huong; Tran, Thi Hong Ha; Xuan, Phuc Nguyen; Ha, Phuong Thu

2016-06-30

Targeting delivery system use natural drugs for tumor cells is an appealing platform help to reduce the side effects and enhance the therapeutic effects of the drug. In this study, we synthesized curcumin (Cur) loaded (D, L Poly lactic - Poly ethylenglycol) micelle (Cur/PLA-PEG) with the ratio of PLA/PEG of 3:1 2:1 1:1 1:2 and 1:3 (w/w) and another micelle modified by folate (Cur/PLA-PEG-Fol) for targeting cancer therapy. The PLA-PEG copolymer was synthesized by ring opening polymerization method. After loading onto the micelle, solubility of Cur increased from 0.38 to 0.73mgml(-1). The average size of prepared Cur/PLA-PEG micelles was from 60 to 69nm (corresponding to the ratio difference of PLA/PEG) and the drug encapsulating efficiency was from 48.8 to 91.3%. Compared with the Cur/PLA-PEG micelles, the size of Cur/PLA-PEG-Fol micelles were from 80 to 86nm and showed better in vitro cellular uptake and cytotoxicity towards HepG2 cells. The cytotoxicity of the NPs however depends much on the PEG component. The results demonstrated that Folate-modified micelles could serve as a potential nano carrier to improve solubility, anti-cancer activity of Cur and targeting ability of the system. Copyright © 2016 Elsevier B.V. All rights reserved.
Novel Dual Mitochondrial and CD44 Receptor Targeting Nanoparticles for Redox Stimuli-Triggered Release

NASA Astrophysics Data System (ADS)

Wang, Kaili; Qi, Mengjiao; Guo, Chunjing; Yu, Yueming; Wang, Bingjie; Fang, Lei; Liu, Mengna; Wang, Zhen; Fan, Xinxin; Chen, Daquan

2018-02-01

In this work, novel mitochondrial and CD44 receptor dual-targeting redox-sensitive multifunctional nanoparticles (micelles) based on oligomeric hyaluronic acid (oHA) were proposed. The amphiphilic nanocarrier was prepared by (5-carboxypentyl)triphenylphosphonium bromide (TPP), oligomeric hyaluronic acid (oHA), disulfide bond, and curcumin (Cur), named as TPP-oHA-S-S-Cur. The TPP targeted the mitochondria, the antitumor drug Cur served as a hydrophobic core, the CD44 receptor targeting oHA worked as a hydrophilic shell, and the disulfide bond acted as a connecting arm. The chemical structure of TPP-oHA-S-S-Cur was characterized by 1HNMR technology. Cur was loaded into the TPP-oHA-S-S-Cur micelles by self-assembly. Some properties, including the preparation of micelles, morphology, redox sensitivity, and mitochondrial targeting, were studied. The results showed that TPP-oHA-S-S-Cur micelles had a mean diameter of 122.4 ± 23.4 nm, zeta potential - 26.55 ± 4.99 mV. In vitro release study and cellular uptake test showed that TPP-oHA-S-S-Cur micelles had redox sensibility, dual targeting to mitochondrial and CD44 receptor. This work provided a promising smart multifunctional nanocarrier platform to enhance the solubility, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs.
Tunable pH and redox-responsive drug release from curcumin conjugated γ-polyglutamic acid nanoparticles in cancer microenvironment.

PubMed

Pillarisetti, Shameer; Maya, S; Sathianarayanan, S; Jayakumar, R

2017-11-01

Tunable pH and redox responsive polymer was prepared using γ-polyglutamic acid (γ-PGA) with linker 3-mercaptopropionic acid (3-MPA) (γ-PGA_SH) via oxidation to obtain redox responsive disulfide (γ-PGA_SS) backbone and adipic acid dihydrazide (ADH) (γ-PGA_SS_ADH) with hydrazide functional group for pH responsiveness. Further curcumin (Cur) was conjugated through hydrazone bond of the γ-PGA_SS_ADH via Schiff base reaction to obtain (γ-PGA_SS_ADH_Cur). The prepared systems were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Qq-TOF-MS/MS) and Solid state nuclear magnetic resonance (SS NMR) techniques. γ-PGA_SS_ADH_Cur formed self-assembled core shell nanoparticles (NPs) in existence of stabilized aqueous medium. γ-PGA_SS_ADH_Cur NPs maintained its stability in physiological condition. NPs tunable Cur release and cytotoxicity were observed for γ-PGA_SS_ADH_Cur NPs in both acidic and redox conditions mimicking the cancer microenvironment. γ-PGA_SS_ADH_Cur NPs uptake study showed via endocytosis mechanism resulted in the lysosomal entrapment of these NPs within the cell. γ-PGA_SS_ADH_Cur NPs exhibited a dual stimuli responsive drug delivery and can be used as a smart and potential drug delivery system in cancer microenvironment. Copyright © 2017 Elsevier B.V. All rights reserved.
A pH-responsive carboxylic β-1,3-glucan polysaccharide for complexation with polymeric guests.

PubMed

Lien, Le Thi Ngoc; Shiraki, Tomohiro; Dawn, Arnab; Tsuchiya, Youichi; Tokunaga, Daisuke; Tamaru, Shun-ichi; Enomoto, Naoya; Hojo, Junichi; Shinkai, Seiji

2011-06-07

The helix-forming nature of β-1,3-glucan polysaccharides is a characteristic that has potential for producing gene carriers, bio-nanomaterials and other chiral nanowires. Herein, carboxylic curdlan (CurCOOH) bearing the β-1,3-polyglucuronic acid structure was successfully prepared from β-1,3-glucan polysaccharide curdlan (Cur) by one-step oxidation using a 4-acetamido-TEMPO/NaClO/NaClO(2) system as the oxidant. The resulting high-molecular-weight CurCOOH was proved to bear the 6-COOH group in 100% purity. The optical rotatory dispersion (ORD) spectra indicated that the obtained CurCOOH behaves as a water-soluble single-strand in various pH aqueous media. This advantage has allowed us to use CurCOOH as a polymeric host to form various macromolecular complexes. For example, complexation of CurCOOH with single-walled carbon nanotubes (SWNTs) resulted in a water-soluble one-dimensional architecture, which formed a dispersion in aqueous solution that was stable for several months, and much more stable than SWNTs complexes of the similar negatively-charged polyacrylic acid (PAA) and polymethacrylic acid (PMAA). It was shown that in the complex, SWNTs are effectively wrapped by a small amount of CurCOOH, enabling them to avoid electrostatic repulsion. This pH-responsive CurCOOH formed a very stable complex with cationic water-soluble polythiophenes (PT-1), which was stabilized not only by the hydrophobic interaction but also by the electrostatic attraction between trimethylammonium cations in PT-1 and dissociated anionic COO(-) groups in CurCOOH. The included PT-1 became CD-active only in the neutral to basic pH region, and the positive Cotton effect suggested that the conjugated main chain is twisted in the right-handed direction. We also found that CurCOOH can interact with polycytidylic acid (poly(C)) only under high NaCl concentrations, the binding and release of which could be controlled by a change in the salt concentration. We believe, therefore, that CurCOOH bearing a dissociable COOH group can act as a new potential polymeric host to construct novel polymeric complexes applicable for gene carriers, biosensors, chiral polymer assemblies, etc.
Trastuzumab- and Fab′ fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo

PubMed Central

Ni, Ling; Zhang, Liping; Yan, Xiuju; Jiang, Ying; Mu, Hongjie; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

2018-01-01

Introduction Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from TMAB)-modified NPs (Fab′-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. Material and methods The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab′-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results The release kinetics showed that both Fab′-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab′-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab′-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2−) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab′-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab′-Cur-NPs was higher than that of TMAB-Cur-NPs. Conclusion Fab′ fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery. PMID:29606874
Development of Food-Grade Curcumin Nanoemulsion and its Potential Application to Food Beverage System: Antioxidant Property and In Vitro Digestion.

PubMed

Joung, Hee Joung; Choi, Mi-Jung; Kim, Jun Tae; Park, Seok Hoon; Park, Hyun Jin; Shin, Gye Hwa

2016-03-01

Curcumin nanoemulsions (Cur-NEs) were developed with various surfactant concentrations by using high pressure homogenization and finally applied to the commercial milk system. Characterization of Cur-NEs was performed by measuring the droplet size and polydispersity index value at different Tween 20 concentrations. The morphology of the Cur-NEs was observed by confocal laser scanning microscopy and transmission electron microscopy. Antioxidant activity and in vitro digestion ability were tested using 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, pH-stat method, and thiobarbituric acid reactive substances assays. Cur-NEs were found to be physically stable for 1 mo at room temperature. The surfactant concentration affects particle formation and droplet size. The mean droplet size decreased from 122 to 90 nm when surfactant concentration increased 3 times. Cur-NEs had shown an effective oxygen scavenging activity. Cur-NEs-fortified milk showed significantly lower lipid oxidation than control (unfortified) milk and milk containing curcumin-free nanoemulsions. These properties make Cur-NEs suitable systems for the beverage industry. © 2016 Institute of Food Technologists®
[Inflammatory cytokines and oxidative stress markers in the inhibition of osteoarthritis by curcumin].

PubMed

Liu, Jun; He, Xiaole; Zhen, Ping; Zhou, Shenghu; Li, Xusheng

2016-05-25

Objective: To observe the influence of matrix metalloproteinases-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), CD47, L-selectin and advanced oxidation proteinproducts (AOPP) in osteoarthritis and the intervention of curcumin. Methods: A total of 20 male C57BL/6 mice (10.05-15.00 g) were randomly divided into control group, OA group, Cur25 group and Cur50 group (intraperitoneal injected 25 μmol/L or 50 μmol/L of curcumin everyday after modeling). After 4 weeks treatment, we observed the morphological changes of the gross specimen by immunohistochemical method, and observed the ultrastructure of cartilage tissue under electron microscope. The expression of MMP-2, MCP-1 and CD47 were detected by western blotting, and L-selectin and AOPP were detected by ELISA and spectrophotometer, respectively. Results: In the cartilage tissue morphology, the chondrocytes of OA group showed obvious change, while Cur25 and Cur50 groups maintained the good cartilage cell membrane intact. Compared with control group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in OA group, Cur25 group and Cur50 group were increased (all P <0.05), while CD47 levels were decreased (all P <0.05). Compared with OA group, the expressions of MMP-2, MCP-1, L-selectin and AOPP in Cur25 group and Cur50 group were decreased (all P <0.05), while CD47 levels were increased (all P <0.05), and such changes were more significant in Cur50 group (all P <0.05). Conclusion: The MMP-2, MCP-1, CD47, L-selectin and AOPP are closely associated with the pathology course of OA. Curcumin has protection effect on cartilage, which can relieve joint cartilage degeneration, reduce cartilage inflammation and increase the metabolic activity of chondrocytes.
SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

PubMed

Yang, Yang; Duan, Weixun; Lin, Yan; Yi, Wei; Liang, Zhenxing; Yan, Juanjuan; Wang, Ning; Deng, Chao; Zhang, Song; Li, Yue; Chen, Wensheng; Yu, Shiqiang; Yi, Dinghua; Jin, Zhenxiao

2013-12-01

Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling. © 2013 Elsevier Inc. All rights reserved.
Geomorphic evidence of active tectonics in the San Gorgonio Pass region of the San Andreas Fault system: an example of discovery-based research in undergraduate teaching

NASA Astrophysics Data System (ADS)

Reinen, L. A.; Yule, J. D.

2014-12-01

Student-conducted research in courses during the first two undergraduate years can increase learning and improve student self-confidence in scientific study, and is recommended for engaging and retaining students in STEM fields (PCAST, 2012). At Pomona College, incorporating student research throughout the geology curriculum tripled the number of students conducting research prior to their senior year that culminated in a professional conference presentation (Reinen et al., 2006). Here we present an example of discovery-based research in Neotectonics, a second-tier course predominantly enrolling first-and second-year students; describe the steps involved in the four week project; and discuss early outcomes of student confidence, engagement and retention. In the San Gorgonio Pass region (SGPR) in southern California, the San Andreas fault undergoes a transition from predominantly strike-slip to a complex system of faults with significant dip-slip, resulting in diffuse deformation and raising the question of whether a large earthquake on the San Andreas could propagate through the region (Yule, 2009). In spring 2014, seven students in the Neotectonics course conducted original research investigating quantifiable geomorphic evidence of tectonic activity in the SGPR. Students addressed questions of [1] unequal uplift in the San Bernardino Mountains, [2] fault activity indicated by stream knick points, [3] the role of fault style on mountain front sinuosity, and [4] characteristic earthquake slip determined via fault scarp degradation models. Students developed and revised individual projects, collaborated with each other on methods, and presented results in a public forum. A final class day was spent reviewing the projects and planning future research directions. Pre- and post-course surveys show increases in students' self-confidence in the design, implementation, and presentation of original scientific inquiries. 5 of 6 eligible students participated in research the following summer, the same 5 enrolled in the follow-up course for Fall 2014, and one student changed her major from the social sciences in order to conduct geology senior thesis research. PCAST: http://www.whitehouse.gov/administration/eop/ostp/pcast/docsreports Reinen et al., CUR-Quarterly, 2006. Yule, Geology, 2009.
Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma.

PubMed

Sharma, S; Zhuang, Y; Ying, Z; Wu, A; Gomez-Pinilla, F

2009-07-21

Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.
Fabrication of a Soybean Bowman-Birk Inhibitor (BBI) Nanodelivery Carrier To Improve Bioavailability of Curcumin.

PubMed

Liu, Chun; Cheng, Fenfen; Yang, Xiaoquan

2017-03-22

Curcumin is a poorly water-soluble drug, and its oral bioavailability is very low. Here, a novel self-assembly nanoparticle delivery carrier has been successfully developed by using soybean Bowman-Birk inhibitor (BBI) to improve the solubility, bioaccessibility, and oral absorption of curcumin. BBI is a unique protein, which can be resistant to the pH range and proteolytic enzymes in the gastrointestinal tract (GIT), bioavailable, and not allergenic. The encapsulation efficiencies (EE) and the loading capacities (LC) of curcumin in the curcumin-loaded BBI nanoparticles (Cur-BBI-NPs, size = 90.09 nm, PDI = 0.103) were 86.17 and 10.31%, respectively. The in vitro bioaccessibility of Cur-BBI-NPs was superior to that of curcumin-loaded sodium caseinate (SC) nanoparticles (Cur-SC-NPs) (as control). Moreover, Cur-BBI-NPs significantly enhanced the bioavailability of curcumin in rats compared with Cur-SC-NPs, and the clathrin-mediated endocytosis pathway probably contributed to the favorable bioavailability of Cur-BBI-NPs, as revealed by the cellular uptake inhibition study.
Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis.

PubMed

Lai, Ching-Shu; Wu, Jia-Ching; Yu, Shih-Feng; Badmaev, Vladimir; Nagabhushanam, Kalyanam; Ho, Chi-Tang; Pan, Min-Hsiung

2011-12-01

Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been demonstrated to be anti-cancerogenic and anti-angiogenic and prevents type II diabetes. In this present study, we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)-induced colon carcinogenesis in mice. All mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and examined. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti-inflammatory activity by decreasing the levels of inducible NOS and COX-2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM-induced Wnt-1 and β-catenin protein expression, as well as the phosphorylation of GSK-3β in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin-43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary THC against AOM-induced colonic tumorigenesis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Tocotrienol Nanoemulsion Platform of Curcumin Elicit Elevated Apoptosis and Augmentation of Anticancer Efficacy against Breast and Ovarian Carcinomas.

PubMed

Steuber, Nelson; Vo, Kathy; Wadhwa, Ritambhara; Birch, Jordan; Iacoban, Paulina; Chavez, Pedro; Elbayoumi, Tamer A

2016-10-26

Vitamin E (VE) tocotrienols (T3), recognized for their cancer-specific anti-proliferative and pro-apoptotic activities, have been previously fabricated into bio-active nanoemulsion (NE) formulations. Here, our viscosity-adapted δ-T3 NE platform was developed to additionally incorporate curcumin (CUR), which is known for its potent suppression of signaling pathways involved in malignant cell growth, survival and metastasis. Thanks to efficient 70:30 wt % surfactant mix of Lutrol F-127:VE-TPGS, in conjunction with optimal CUR loading, a prototype CUR in δ-T3 NE was successfully prepared. Model CUR/δ-T3 NE demonstrated excellent nano-scale aspects (mean particle size = 261 nm, PDI = 0.27, and ζ-potential = -35 mV), pharmaceutical stability, and controlled release properties. Suitability for systemic administration was also verified via standardized in vitro biocompatibility and hemocompatibility assays. In two human cancer cells (MCF-7 and OVCAR-8), our CUR/δ-T3 NE prominently suppressed constitutive NF-κB activation, and significantly induced apoptosis. Finally, the combined CUR/δ-T3 NE produced superior cytotoxicity profiles, in concentration- and time-dependent manners ( p ≤ 0.05), at least three to four folds lower IC 50 than in closest CUR control. The strong synergism, estimated in both cultured carcinomas, revealed the augmented therapeutic efficacy of our CUR/δ-T3 NE combined platform, supporting its strong potential towards pharmaceutical development for cancer therapy.

Common Rule Revisions: The Saga Continues

EPA Science Inventory

The Common Rule regulations that govern human subjects research were revised in 2017, after a 6-year rulemaking process. Changes were made in many areas, including informed consent, continuing review, exemptions and multi-site research, with an effective date of January 2018 (cur...
Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...
Foliar insecticides for the control of curly top in Idaho sugar beet, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. The neonicotiono...
Beet curly top resistance in USDA-ARS plant introduction lines, 2017

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...
Production and regulation of functional amyloid curli fimbriae by Shiga toxin-producing Escherichia coli

USDA-ARS?s Scientific Manuscript database

Functional amyloid, in the form of adhesive fimbrial proteins termed curli, was first described in Salmonella and Escherichia coli. Curli fibers adhere to various host cells and structural proteins, interact with components of the host immune system, and participate in biofilm formation. Shiga toxin...
Beet curly top resistance in USDA-ARS plant introduction lines, 2016

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to iden...
Beet curly top resistance in USDA-ARS Kimberly germplasm lines, 2015

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify no...
Improving intestinal absorption and oral bioavailability of curcumin via taurocholic acid-modified nanostructured lipid carriers.

PubMed

Tian, Cihui; Asghar, Sajid; Wu, Yifan; Chen, Zhipeng; Jin, Xin; Yin, Lining; Huang, Lin; Ping, Qineng; Xiao, Yanyu

2017-01-01

The expression of multiple receptors on intestinal epithelial cells enables an actively targeted carrier to significantly enhance the oral delivery of payloads. Conjugating the receptors' ligands on the surfaces of a particulate-delivery system allows site-specific targeting. Here, we used taurocholic acid (TCA) as a ligand for uptake of nanostructured lipid carriers (NLCs) mediated by a bile-acid transporter to improve oral bioavailability of curcumin (Cur). First, synthesis of TCA-polyethylene glycol 100-monostearate (S100-TCA) was carried out. Then, the physical and chemical properties of S100-TCA-modified Cur-loaded NLCs (Cur-TCA NLCs) with varying levels of S100-TCA modifications were investigated. Small particle size (<150 nm), high drug encapsulation (>90%), drug loading (about 3%), negative ζ-potential (-7 to -3 mV), and sustained release were obtained. In situ intestinal perfusion studies demonstrated improved absorption rate and permeability coefficient of Cur-TCA NLCs. Depending on the degree of modification, Cur-TCA NLCs displayed about a five- to 15-fold higher area under the curve in rats after oral administration than unmodified Cur NLCs, which established that the addition of S100-TCA to the NLCs boosted absorption of Cur. Further investigations of TCA NLCs might reveal a bright future for effective oral delivery of poorly bioavailable drugs.
Experimental investigation and oral bioavailability enhancement of nano-sized curcumin by using supercritical anti-solvent process.

PubMed

Anwar, Mohammed; Ahmad, Iqbal; Warsi, Musarrat H; Mohapatra, Sharmistha; Ahmad, Niyaz; Akhter, Sohail; Ali, Asgar; Ahmad, Farhan J

2015-10-01

The biomedical applications of curcumin (CUR) are limited due to its poor oral bioavailability. In this work, CUR nanoparticles were successfully prepared by combining the supercritical anti-solvent (SAS) process with Tween 80 as a solubilizing agent and permeation enhancer. Different processing parameters that can govern the mean particle size and size distribution of nanoparticles were well investigated by manipulating the types of solvents, mixing vessel pressure, mixing vessel temperature, CO2 flow rate, solution flow rate and solution concentration. Solid state characterization was done by Fourier Transform infrared spectroscopy, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy, and powder X-ray diffraction study. Solubility and dissolution profile of SAS-processed CUR were found to be significantly increased in comparison with native CUR. Further, a validated ultra-performance liquid chromatographic method with quadrupole-time of flight-mass spectrometry was developed to investigate the pharmacokinetic parameters after a single oral dose (100mg/kg) administration of CUR (before/after SAS-processed) in male Wistar rats. From the plasma concentration vs. time profile graph, oral bioavailability of SAS-processed CUR was found to be increased approximately 11.6-fold (p<0.001) as compared to native CUR. Copyright © 2015 Elsevier B.V. All rights reserved.
Preparation and anti-cancer activity of polymer-encapsulated curcumin nanoparticles

NASA Astrophysics Data System (ADS)

Thu Ha, Phuong; Huong Le, Mai; Nhung Hoang, Thi My; Thu Huong Le, Thi; Quang Duong, Tuan; Tran, Thi Hong Ha; Tran, Dai Lam; Phuc Nguyen, Xuan

2012-09-01

Curcumin (Cur) is a yellow compound isolated from rhizome of the herb curcuma longa. Curcumin possesses antioxidant, anti-inflammatory, anti-carcinogenic and antimicrobial properties, and suppresses proliferation of many tumor cells. However, the clinical application of curcumin in cancer treatment is considerably limited due to its serious poor delivery characteristics. In order to increase the hydrophilicity and drug delivery capability, we encapsulated curcumin into copolymer PLA-TPGS, 1,3-beta-glucan (Glu), O-carboxymethyl chitosan (OCMCs) and folate-conjugated OCMCs (OCMCs-Fol). These polymer-encapsulated curcumin nanoparticles (Cur-PLA-TPGS, Cur-Glu, Cur-OCMCs and Cur-OCMCs-Fol) were characterized by infrared (IR), fluorescence (FL), photoluminescence (PL) spectra, field emission scanning electron microscopy (FE-SEM), and found to be spherical particles with an average size of 50-100 nm, being suitable for drug delivery applications. They were much more soluble in water than not only free curcumin but also other biodegradable polymer-encapsulated curcumin nanoparticles. The anti-tumor promoting assay was carried out, showing the positive effects of Cur-Glu and Cur-PLA-TPGS on tumor promotion of Hep-G2 cell line in vitro. Confocal microscopy revealed that the nano-sized curcumin encapsulated by polymers OCMCs and OCMCs-Fol significantly enhanced the cellular uptake (cancer cell HT29 and HeLa).
Characterization of Interactions between Curcumin and Different Types of Lipid Bilayers by Molecular Dynamics Simulation.

PubMed

Lyu, Yuan; Xiang, Ning; Mondal, Jagannath; Zhu, Xiao; Narsimhan, Ganesan

2018-03-01

Curcumin (CUR) is a natural food ingredient with known ability to target microbial cell membrane. In this study, the interactions of CUR with different types of model lipid bilayers (POPE, POPG, POPC, DOPC, and DPPE), mixtures of model lipid bilayers (POPE/POPG), and biological membrane mimics (Escherichia coli and yeast) were investigated by all-atom explicit solvent molecular dynamics (MD) simulation. CUR readily inserts into different types of model lipid bilayer systems in the liquid crystalline state, staying in the lipid tails region near the interface of lipid head and lipid tail. Parallel orientation to the membrane surface is found to be more probable than perpendicular for CUR, as indicated by the tilt angle distribution. This orientation preference is less significant as the fraction of POPE is increased in the system, likely due to the better water solvation of perpendicular orientation in the POPE bilayer. In E. coli and yeast bilayers, tilt angle distributions were similar to that for POPE/POPG mixed bilayer, with water hydration number around CUR for the former being higher. Insertion of CUR resulted in membrane thinning. The results from these simulations provide insights into the possible differences in membrane disrupting activity of CUR against different types of microorganisms.
Seed Transmission of Beet Curly Top Virus and Beet Curly Top Iran Virus in a Local Cultivar of Petunia in Iran

PubMed Central

Anabestani, Ameneh; Behjatnia, Seyed Ali Akbar; Izadpanah, Keramat; Tabein, Saeid

2017-01-01

Beet curly top virus (BCTV) and beet curly top Iran virus (BCTIV) are known as the causal agents of curly top disease in beet and several other dicotyledonous plants in Iran. These viruses are transmitted by Circulifer species, and until now, there has been no confirmed report of their seed transmission. A percentage (38.2–78.0%) of the seedlings developed from the seeds of a petunia local cultivar under insect-free conditions showed stunting, interveinal chlorosis, leaf curling, and vein swelling symptoms, and were infected by BCTV when tested by PCR. Presence of BCTV in seed extracts of petunia local cultivar was confirmed by PCR and IC-PCR, followed by sequencing. Agroinoculation of curly top free petunia plants with a BCTV infectious clone resulted in BCTV infection of plants and their developed seeds. These results show the seed infection and transmission of BCTV in a local cultivar of petunia. Similar experiments performed with BCTIV showed that this virus is also seed transmissible in the same cultivar of petunia, although with a lower rate (8.8–18.5%). Seed transmission of curly top viruses may have significant implications in the epidemiology of these viruses. PMID:29035342
Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

PubMed

Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

2017-01-01

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.
Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury.

PubMed

Kalani, Anuradha; Chaturvedi, Pankaj; Kamat, Pradip K; Maldonado, Claudio; Bauer, Philip; Joshua, Irving G; Tyagi, Suresh C; Tyagi, Neetu

2016-10-01

We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo cur ), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo cur for 7days. Similarly, two sham groups were made and one group received MESC-exo cur treatment. The study determined that MESC-exo cur treatment reduced neurological score, infarct volume and edema following IR-injury. As compared to untreated IR group, MESC-exo cur treated-IR group showed reduced inflammation and N-methyl-d-aspartate receptor expression. Treatment of MESC-exo cur also reduced astrocytic GFAP expression and alleviated the expression of NeuN positive neurons in IR-injured mice. In addition, MESC-exo cur treatment restored vascular endothelial tight (claudin-5 and occludin) and adherent (VE-cadherin) junction proteins in IR-injured mice as compared to untreated IR-injured mice. These results suggest that combining the potentials of embryonic stem cell exosomes and curcumin can help neurovascular restoration following ischemia-reperfusion injury in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.
Potential therapeutic and protective effect of curcumin against stroke in the male albino stroke-induced model rats.

PubMed

Zhang, Yuanyuan; Yan, Yi; Cao, Yi; Yang, Yongtao; Zhao, Qing; Jing, Rui; Hu, Jiayi; Bao, Juan

2017-08-15

The present study was carried out to understand the therapeutic effect of curcumin (CUR) against stroke in the experimental animal model. The study investigates the healing effect of CUR on mitochondrial dysfunction and inflammation. Male albino, Wistar strain rats were used for the induction of middle cerebral artery occlusion (MCAO), and reperfusion. Enzyme-linked immunosorbent assay (ELISA) was used for the determination of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the brain region. Western blot analysis was used to determine the protein expression levels of Bax, Bcl-2, p53, and Sirt1. The water level was determined in brain region by using standard method. Experimental results indicated that the use of CUR significantly reduced brain edema and water content. IL-6 and TNF-α were significantly reduced in the brain region following use of CUR. Mitochondrial membrane potential (MMP) also reduced significantly after CUR treatment. Protein expression of p53 and Bax were significantly reduced, whereas Bcl-2 and Sirt1 were increased following CUR treatment. Taking all these data together, it is suggested that the use of CUR may be a potential therapeutic agent for the treatment of stroke. Copyright © 2017 Elsevier Inc. All rights reserved.
Formulation optimization, characterization, and evaluation of in vitro cytotoxic potential of curcumin loaded solid lipid nanoparticles for improved anticancer activity.

PubMed

Rompicharla, Sri Vishnu Kiran; Bhatt, Himanshu; Shah, Aashma; Komanduri, Neeraja; Vijayasarathy, Dhanya; Ghosh, Balaram; Biswas, Swati

2017-11-01

The aim of the present research was to develop a novel, biocompatible, amenable to industrial scale up and affordable solid lipid nanoparticles (SLN) preparation of curcumin and evaluate the therapeutic efficacy in vitro using cancer cells. We have incorporated cholesterol as the lipid to prepare SLN along with the Poloxamer-188 as stabilizer. High shear homogenization was used to prepare the SLN and formulation was optimized using Quality by Design The optimized Chol CUR SLN exhibited a narrow size distribution with a particle size of 166.4±3.5nm. Percentage encapsulation (%EE) was found to be 76.9±1.9%. The SLN were further characterized by DSC, FTIR, XRD and drug release. In vitro cell studies in MDA-MB-231 (Human Breast cancer) cell line revealed that the Chol CUR SLN showed superior cytotoxicity and uptake in comparison to the free curcumin. Furthermore, Chol CUR SLN induced a significantly higher apoptosis compared to free CUR treatment. These results indicated that the curcumin encapsulated in Chol SLN was able to significantly improve the cytotoxic potential and induction of apoptosis in MDA-MB-231 cells. The promising result from our study could lead a further exploration of this nanoparticle formulation to be utilized clinically for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.
Transepithelial Transport of Curcumin in Caco-2 Cells Is significantly Enhanced by Micellar Solubilisation.

PubMed

Frank, Jan; Schiborr, Christina; Kocher, Alexa; Meins, Jürgen; Behnam, Dariush; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

2017-03-01

Curcumin, the active constituent of Curcuma longa L. (family Zingiberaceae), has gained increasing interest because of its anti-cancer, anti-inflammatory, anti-diabetic, and anti-rheumatic properties associated with good tolerability and safety up to very high doses of 12 g. Nanoscaled micellar formulations on the base of Tween 80 represent a promising strategy to overcome its low oral bioavailability. We therefore aimed to investigate the uptake and transepithelial transport of native curcumin (CUR) vs. a nanoscaled micellar formulation (Sol-CUR) in a Caco-2 cell model. Sol-CUR afforded a higher flux than CUR (39.23 vs. 4.98 μg min -1 cm -2 , respectively). This resulted in a higher P app value of 2.11 × 10 -6 cm/s for Sol-CUR compared to a P app value of 0.56 × 10 -6 cm/s for CUR. Accordingly a nearly 9.5 fold higher amount of curcumin was detected on the basolateral side at the end of the transport experiments after 180 min with Sol-CUR compared to CUR. The determined 3.8-fold improvement in the permeability of curcumin is in agreement with an up to 185-fold increase in the AUC of curcumin observed in humans following the oral administration of the nanoscaled micellar formulation compared to native curcumin. The present study demonstrates that the enhanced oral bioavailability of micellar curcumin formulations is likely a result of enhanced absorption into and increased transport through small intestinal epithelial cells.
Curcumin improves regulatory T cells in gut-associated lymphoid tissue of colitis mice

PubMed Central

Zhao, Hai-Mei; Xu, Rong; Huang, Xiao-Ying; Cheng, Shao-Min; Huang, Min-Fang; Yue, Hai-Yang; Wang, Xin; Zou, Yong; Lu, Ai-Ping; Liu, Duan-Yong

2016-01-01

AIM: To explore the probable pathway by which curcumin (Cur) regulates the function of Treg cells by observing the expression of costimulatory molecules of dendritic cells (DCs). METHODS: Experimental colitis was induced by administering 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)/ethanol solution. Forty male C57BL/6 mice were randomly divided into four groups: normal, TNBS + Cur, TNBS + mesalazine (Mes) and TNBS groups. The mice in the TNBS + Cur and TNBS +Mes groups were treated with Cur and Mes, respectively, while those in the TNBS group were treated with physiological saline for 7 d. After treatment, the curative effect of Cur was evaluated by colonic weight, colonic length, weight index of the colon, and histological observation and score. The levels of CD4+CD25+Foxp3+ T cells (Treg cells) and costimulatory molecules of DCs were measured by flow cytometry. Also, related cytokines were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cur alleviated inflammatory injury of the colonic mucosa, decreased colonic weigh and histological score, and restored colonic length. The number of Treg cells was increased, while the secretion of TNF-α, IL-2, IL-6, IL-12 p40, IL-17 and IL-21 and the expression of costimulatory molecules (CD205, CD54 [ICAM-1], TLR4, CD252[OX40 L], CD256 [RANK] and CD254 [RANK L]) of DCs were notably inhibited in colitis mice treated with Cur. CONCLUSION: Cur potentially modulates activation of DCs to enhance the suppressive functions of Treg cells and promote the recovery of damaged colonic mucosa in inflammatory bowel disease. PMID:27340353
Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier

NASA Astrophysics Data System (ADS)

Chen, Daquan; Song, Xiaoyan; Wang, Kaili; Guo, Chunjing; Yu, Yueming; Fan, Huaying; Zhao, Feng

2017-12-01

In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H-NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential - 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.
Length of efficacy for control of curly top in sugar beet with seed foliar insecticides

USDA-ARS?s Scientific Manuscript database

Curly top in sugar beet caused by Beet curly top virus (BCTV) is an important yield limiting disease that can be reduced via neonicotinoid and pyrethroid insecticides. However the length of efficacy of these insecticides is poorly understood, so a series of field experiments was conducted with the ...

Influence of curli expression on biofilm formation and attachment to plant surface by shiga toxigenic E. coli

USDA-ARS?s Scientific Manuscript database

Shiga-toxigenic Escherichia coli O157:H7 (STEC) outbreaks have been linked to consumption of fresh produce. Bacteria extracellular appendages, such as curli fibers and cellulose may play critical role in STEC biofilm formation and adherence to plant surface. We determined cellulose and curli product...
Beet curly top resistance in USDA-ARS Kimberly sugar beet germplasm lines, 2016

USDA-ARS?s Scientific Manuscript database

Curly top caused by Beet curly top virus is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify no...
Impact of curly top host plants on accumulation, competitiveness, and durability of curtovirus species.

USDA-ARS?s Scientific Manuscript database

Curly top disease, caused by viruses in the genus, Curtovirus, has affected sugarbeet production throughout much of the West for over a century; however, over that period the viruses responsible for causing the disease have changed. The two curly top virus species currently affecting production, Bee...
Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

USDA-ARS?s Scientific Manuscript database

We previously showed that curcumin (CUR) may increase lipid accumulation in cultured THP-1 monocytes/macrophages, but tetrahydrocurcumin (THC), an in vivo metabolite of CUR, had no such effect. In the present study, we have hypothesized that different cellular uptake and/or metabolism of CUR and THC...
Management of curly top in sugarbeet with seed and foliar insecticides

USDA-ARS?s Scientific Manuscript database

Curly top in sugarbeet can result in severe yield losses and is caused by Beet severe curly top virus (BSCTV) and other closely related Curtovirus spp. which are vectored by the beet leafhopper. Neonicotinoid seed treatments (Cruiser, NipsIt, and Poncho) have been shown to be an effective supplemen...
Management of curly top in sugar beet with seed and foliar insecticides

USDA-ARS?s Scientific Manuscript database

Curly top in sugar beet can result in severe yield losses and is caused by Beet severe curly top virus (BSCTV) and other closely related Curtovirus spp. which are vectored by the beet leafhopper. Neonicotinoid seed treatments (Cruiser, NipsIt, and Poncho) have been shown to be an effective suppleme...
Structural characterization, formation mechanism and stability of curcumin in zein-lecithin composite nanoparticles fabricated by antisolvent co-precipitation.

PubMed

Dai, Lei; Sun, Cuixia; Li, Ruirui; Mao, Like; Liu, Fuguo; Gao, Yanxiang

2017-12-15

Curcumin (Cur) exhibits a range of bioactive properties, but its application is restrained due to its poor water solubility and sensitivity to environmental stresses. In this study, zein-lecithin composite nanoparticles were fabricated by antisolvent co-precipitation technique for delivery of Cur. The result showed that the encapsulation efficiency of Cur was significantly enhanced from 42.03% in zein nanoparticles to 99.83% in zein-lecithin composite nanoparticles. The Cur entrapped in the nanoparticles was in an amorphous state confirmed by differential scanning calorimetry and X-ray diffraction. Fourier transform infrared analysis revealed that hydrogen bonding, electrostatic interaction and hydrophobic attraction were the main interactions among zein, lecithin, and Cur. Compared with single zein and lecithin nanoparticles, zein-lecithin composite nanoparticles significantly improved the stability of Cur against thermal treatment, UV irradiation and high ionic strength. Therefore, zein-lecithin composite nanoparticles could be a potential delivery system for water-insoluble bioactive compounds with enhanced encapsulation efficiency and chemical stability. Copyright © 2017 Elsevier Ltd. All rights reserved.
Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

NASA Astrophysics Data System (ADS)

Shao, Xiao-Ru; Wei, Xue-Qin; Zhang, Shu; Fu, Na; Lin, Yun-Feng; Cai, Xiao-Xiao; Peng, Qiang

2017-08-01

Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein, we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm, comparable physical stabilities and analogous in vitro release profiles. Interestingly, the chemical stability of liposomal curcumin in 50% fetal bovine serum and its anticancer efficacy in vitro are both micro-environmental pH-dependent (Cur-LP-2.5 > Cur-LP-5.0 > Cur-LP-7.4). This serum stability still has space to be further enhanced to improve the applicability of Cur-LP. In conclusion, creating an acidic micro-environment in the internal chamber of liposome is feasible and efficient to improve the chemical stability of pH-sensitive payloads.
CD14 Protein Acts as an Adaptor Molecule for the Immune Recognition of Salmonella Curli Fibers*

PubMed Central

Rapsinski, Glenn J.; Newman, Tiffanny N.; Oppong, Gertrude O.; van Putten, Jos P. M.; Tükel, Çagla

2013-01-01

Amyloids, protein aggregates with a cross β-sheet structure, contribute to inflammation in debilitating disorders, including Alzheimer's disease. Enteric bacteria also produce amyloids, termed curli, contributing to inflammation during infection. It has been demonstrated that curli and β-amyloid are recognized by the immune system via the Toll-like receptor (TLR) 2/TLR1 complex. Here we investigated the role of CD14 in the immune recognition of bacterial amyloids. We used HeLa 57A cells, a human cervical cancer cell line containing a luciferase reporter gene under the control of an NF-κB promoter. When HeLa 57A cells were transiently transfected with combinations of human expression vectors containing genes for TLR2, TLR1, and CD14, membrane-bound CD14 enhanced NF-κB activation through the TLR2/TLR1 complex stimulated with curli fibers or recombinant CsgA, the curli major subunit. Similarly, soluble CD14 augmented the TLR2/TLR1 response to curli fibers in the absence of membrane-bound CD14. We further revealed that IL-6 and nitric oxide production were significantly higher by wild-type (C57BL/6) bone marrow-derived macrophages compared with TLR2-deficient or CD14-deficient bone marrow-derived macrophages when stimulated with curli fibers, recombinant CsgA, or synthetic CsgA peptide, CsgA-R4–5. Binding assays demonstrated that recombinant TLR2, TLR1, and CD14 bound purified curli fibers. Interestingly, CD14-curli interaction was specific to the fibrillar form of the amyloid, as demonstrated by using synthetic CsgA peptides proficient and deficient in fiber formation, respectively. Activation of the TLR2/TLR1/CD14 trimolecular complex by amyloids provides novel insights for innate immunity with implications for amyloid-associated diseases. PMID:23548899
Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

PubMed Central

Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

2016-01-01

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287
Antagonism between curcumin and the topoisomerase II inhibitor etoposide

PubMed Central

Saleh, Ekram M.; El-awady, Raafat A; Eissa, Nadia A.; Abdel-Rahman, Wael M.

2012-01-01

The use of combinations of chemotherapy and natural products has recently emerged as a new method of cancer therapy, relying on the capacity of certain natural compounds to trigger cell death with low doses of chemotherapeutic agents and few side effects. The current study aims to evaluate the modulatory effects of curcumin (CUR), Nigella sativa (NS) and taurine on etoposide (ETP) cytotoxicity in a panel of cancer cell lines and to identify their underlying mechanisms. CUR alone showed potent antitumor activity, but surprisingly, its interaction with ETP was antagonistic in four out of five cancer cell lines. Neither taurine nor Nigella sativa affect the sensitivity of cancer cells to ETP. Examination of the DNA damage response machinery (DDR) showed that both ETP and CUR elicited DNA double-strand breaks (DSB) and evoked γ-H2AX foci formation at doses as low as 1 µg/ml. Cell cycle analysis revealed S phase arrest after ETP or CUR application, whereas co-treatment with ETP and CUR led to increased arrest of the cell cycle in S phase (MCF-7 cells) or the accumulation of cells in G2/M phases (HCT116, and HeLa cells). Furthermore, cotreatment with ETP and CUR resulted in modulation of the level of DNA damage induction and repair compared with either agent alone. Electron microscopic examination demonstrated that different modalities of cell death occurred with each treatment. CUR alone induced autophagy, apoptosis and necrosis, whereas ETP alone or in combination with CUR led to apoptosis and necrosis. Conclusions: Cotreatment with ETP and CUR resulted in an antagonistic interaction. This antagonism is related, in part, to the enhanced arrest of tumor cells in both S and G2/M phases, which prevents the cells from entering M-phase with damaged DNA and, consequently, prevents cell death from occurring. This arrest allows time for the cells to repair DNA damage so that cell cycle -arrested cells can eventually resume cell cycle progression and continue their physiological program. PMID:22895066
Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis.

PubMed

Sharma, Monika; Manoharlal, Raman; Negi, Arvind Singh; Prasad, Rajendra

2010-08-01

We have shown previously that pure polyphenol curcumin I (CUR-I) shows antifungal activity against Candida species. By employing the chequerboard method, filter disc and time-kill assays, in the present study we demonstrate that CUR-I at non-antifungal concentration interacts synergistically with azoles and polyenes. For this, pure polyphenol CUR-I was tested for synergy with five azole and two polyene drugs - fluconazole (FLC), miconazole, ketoconazole (KTC), itraconazole (ITR), voriconazole (VRC), nystatin (NYS) and amphotericin B (AMB) - against 21 clinical isolates of Candida albicans with reduced antifungal sensitivity, as well as a drug-sensitive laboratory strain. Notably, there was a 10-35-fold drop in the MIC(80) values of the drugs when CUR-I was used in combination with azoles and polyenes, with fractional inhibitory concentration index (FICI) values ranging between 0.09 and 0.5. Interestingly, the synergistic effect of CUR-I with FLC and AMB was associated with the accumulation of reactive oxygen species, which could be reversed by the addition of an antioxidant such as ascorbic acid. Furthermore, the combination of CUR-I and FLC/AMB triggered apoptosis that could also be reversed by ascorbic acid. We provide the first evidence that pure CUR-I in combination with azoles and polyenes represents a novel therapeutic strategy to improve the activity of common antifungals.
Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability.

PubMed

Onoue, Satomi; Takahashi, Haruki; Kawabata, Yohei; Seto, Yoshiki; Hatanaka, Junya; Timmermann, Barbara; Yamada, Shizuo

2010-04-01

Considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders, however, the therapeutic potential of curcumin could often be limited by its poor solubility, bioavailability, and photostability. To overcome these drawbacks, efficacious formulations of curcumin, including nanocrystal solid dispersion (CSD-Cur), amorphous solid dispersion (ASD-Cur), and nanoemulsion (NE-Cur), were designed with the aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the prepared formulations were characterized by scanning/transmission electron microscope for morphological analysis, laser diffraction, and dynamic light scattering for particle size analysis, and polarized light microscope, powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. In dissolution tests, all curcumin formulations exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin. Significant improvement in pharmacokinetic behavior was observed in the newly developed formulations, as evidenced by 12- (ASD-Cur), 16- (CSD-Cur), and 9-fold (NE-Cur) increase of oral bioavailability. Upon photochemical characterization, curcumin was found to be photoreactive and photodegradable in the solution state, possibly via type 2 photochemical reaction, whereas high photochemical stability was seen in the solid formulations, especially CSD-Cur. On the basis of these observations, taken together with dissolution and pharmacokinetic behaviors, CSD strategy would be efficacious to enhance bioavailability of curcumin with high photochemical stability. 2009 Wiley-Liss, Inc. and the American Pharmacists Association
Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in Cultured Human Glioblastoma Cells than Does Natural Curcumin

PubMed Central

Al-Gharaibeh, Abeer; Kolli, Nivya

2017-01-01

Despite recent advancements in cancer therapies, glioblastoma multiforme (GBM) remains largely incurable. Curcumin (Cur), a natural polyphenol, has potent anticancer effects against several malignancies, including metastatic brain tumors. However, its limited bioavailability reduces its efficiency for treating GBM. Recently, we have shown that solid lipid Cur particles (SLCPs) have greater bioavailability and brain tissue penetration. The present study compares the efficiency of cell death by Cur and/or SLCPs in cultured GBM cells derived from human (U-87MG) and mouse (GL261) tissues. Several cell viability and cell death assays and marker proteins (MTT assay, annexin-V staining, TUNEL staining, comet assay, DNA gel electrophoresis, and Western blot) were investigated following the treatment of Cur and/or SLCP (25 μM) for 24–72 h. Relative to Cur, the use of SLCP increased cell death and DNA fragmentation, produced longer DNA tails, and induced more fragmented nuclear lobes. In addition, cultured GBM cells had increased levels of caspase-3, Bax, and p53, with decreases in Bcl2, c-Myc, and both total Akt, as well as phosphorylated Akt, when SLCP, rather Cur, was used. Our in vitro work suggests that the use of SLCP may be a promising strategy for reversing or preventing GBM growth, as compared to using Cur. PMID:29359011
Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis.

PubMed

Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

2015-01-01

Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.
Beet curly top virus strains associated with sugar beet in Idaho, Oregon, and a survey collection

USDA-ARS?s Scientific Manuscript database

Curly top of sugar beet is a serious yield limiting disease in semi-arid production areas caused by Beet curly top virus (BCTV) and vectored by the beet leafhopper (Circulifer tennellus). The primary means of control for BCTV is host resistance, but effectiveness of resistance can vary among BCTV s...
Natural rpoS mutations contribute to the phenotypic heterogeneity of clonal populations in Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

We previously reported the distinct acid resistance between the curli-producing (C+) and curli-deficient (C-) variants of E. coli O157:H7, although the curli fimbriae were not associated with this intra-strain phenotypic divergence. Here we investigated the underlying molecular mechanism by examinin...
Curli fimbriae are conditionally required in Escherichia coli O157:H7 for initial attachment and biofilm formation

USDA-ARS?s Scientific Manuscript database

Several species of enteric pathogens produce curli fimbriae, which may affect their interaction with surfaces and other microbes in nonhost environments. Here we used two E. coli O157:H7 outbreak strains with distinct genotypes to understand the role of curli in surface attachment and biofilm format...
Phage insertion in mlrA and variations in rpoS limit curli expression and biofilm formation in Escherichia coli serotype O157:H7

USDA-ARS?s Scientific Manuscript database

Biofilm formation in Escherichia coli is a tightly controlled process requiring the expression of adhesive curli fibers and certain polysaccharides such as cellulose. The transcriptional regulator CsgD is central to biofilm formation, controlling the expression of the curli structural and export pro...
Transpositional inactivation of gadW enhances curli production and biofilm formation in Enterohemorrhagic Escherichia coli O157:H7

USDA-ARS?s Scientific Manuscript database

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 has been shown to produce variants that either express or are repressed in the expression of curli fimbriae promoting bacterial attachment, aggregation, and biofilm formation. The variant expression of curli fimbriae in some instances could result fr...

Curcumin-functionalized silk biomaterials for anti-aging utility.

PubMed

Yang, Lei; Zheng, Zhaozhu; Qian, Cheng; Wu, Jianbing; Liu, Yawen; Guo, Shaozhe; Li, Gang; Liu, Meng; Wang, Xiaoqin; Kaplan, David L

2017-06-15

Curcumin is a natural antioxidant that is isolated from turmeric (Curcuma longa) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. Copyright © 2017 Elsevier Inc. All rights reserved.
Long-Circulating Curcumin-Loaded Liposome Formulations with High Incorporation Efficiency, Stability and Anticancer Activity towards Pancreatic Adenocarcinoma Cell Lines In Vitro.

PubMed

Mahmud, Mohamed; Piwoni, Adriana; Filipczak, Nina; Janicka, Martyna; Gubernator, Jerzy

2016-01-01

The incorporation of hydrophobic drugs into liposomes improve their bioavailability and leads to increased stability and anticancer activity, along with decreased drug toxicity. Curcumin (Cur) is a natural polyphenol compound with a potent anticancer activity in pancreatic adenocarcinoma (PA). In the present study, different types of Cur-loaded liposomal formulations were prepared and characterized in terms of size, shape, zeta potential, optimal drug-to-lipid ratio and stability at 4°C, 37°C; and in human plasma in vitro. The best formulation in terms of these parameters was PEGylated, cholesterol-free formulation based upon hydrogenated soya PC (HSPC:DSPE-PEG2000:Cur, termed H5), which had a 0.05/10 molar ratio of drug-to-lipid, was found to be stable and had a 96% Cur incorporation efficiency. All Cur-loaded liposomal formulations had potent anticancer activity on the PA cancer cell lines AsPC-1 and BxPC-3, and were less toxic to a normal cell line (NHDF). Furthermore, apoptosis-induction induced by Cur in PA cells was associated with morphological changes including cell shrinkage, cytoplasmic blebbing, irregularity in shape and the externalization of cell membrane phosphatidylserine, which was preceded by an increase in intracellular reactive oxygen species (ROS) generation and caspase 3/7 activation. Because the liposomal formulations tested here, especially the H5 variant which exhibited slow release of the Cur in the human plasma test, the formulation may be stable enough to facilitate the accumulation of pharmacologically active amounts of Cur in target cancer tissue by EPR. Therefore, our formulations could serve as a promising therapeutic approach for pancreatic cancer and other cancers.
Beet curly top virus strains associated with sugar beet in Idaho, Oregon, and a Western U.S. collection

USDA-ARS?s Scientific Manuscript database

Curly top of sugar beet is a serious, yield limiting disease in semi-arid production areas caused by Beet curly top virus (BCTV) and transmitted by the beet leafhopper. One of the primary means of control for BCTV in sugar beet is host resistance but effectiveness of resistance can vary among BCTV ...
Stx1 prophage excision in Escherichia coli strain PA20 confers strong curli and biofilm formation by restoring native mlrA

USDA-ARS?s Scientific Manuscript database

Prophage insertions in Escherichia coli O157:H7 mlrA contribute to the low expression of curli fimbriae and biofilm observed in many clinical isolates. Varying levels of CsgD-dependent curli/biofilm expression are restored to strains bearing prophage insertions in mlrA by mutation of regulatory gene...
Role of curli and cellulose expression by Escherichia coli O157:H7 on the cell’s ability to attach to spinach

USDA-ARS?s Scientific Manuscript database

Shiga-toxigenic Escherichia coli O157:H7 (STEC) outbreaks have been linked to consumption of fresh produce. Cellular appendages, such as curli fibers have been suggested to be involved in STEC persistence in fresh produce as these curli are critical in biofilm formation and adherence to animal cell...
Determination of acidity constants of curcumin in aqueous solution and apparent rate constant of its decomposition

NASA Astrophysics Data System (ADS)

Bernabé-Pineda, Margarita; Ramírez-Silva, María. Teresa; Romero-Romo, Mario; González-Vergara, Enrique; Rojas-Hernández, Alberto

2004-04-01

The stability of curcumin (H 3Cur) in aqueous media is improved when the systems in which it is present are at high pH values (higher than 11.7), fitting a model describable by a pseudo-zero order with a rate constant k' for the disappearance of the Cur 3- species of 1.39 (10 -9) M min -1. There were three acidity constants measured for the curcumin as follows: p KA3=10.51±0.01 corresponding to the equilibrium HCur 2-=Cur 3-+H +, a p KA2=9.88±0.02 corresponding to the equilibrium H 2Cur -=HCur -2+H +. These p KA values were attributed to the hydrogen of the phenol part of the curcumin, while the p KA1=8.38±0.04 corresponds to the equilibrium H 3Cur=H 2Cur -+H + and is attributed the acetylacetone type group. Formation of quinoid structures play an important role in the tautomeric forms of the curcumin in aqueous media, which makes the experimental values differ from the theoretically calculated ones, depending on the conditions adopted in the study.
MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1.

PubMed

Fan, Haoning; Shao, Meng; Huang, Shaohui; Liu, Ying; Liu, Jie; Wang, Zhiyuan; Diao, Jianxin; Liu, Yuanliang; Tong, L I; Fan, Qin

2016-06-01

Curcumin (Cur) exhibits radiosensitization effects to a variety of malignant tumors. The present study investigates the radiosensitizing effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the radiosensitizing effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the radiosensitizing effect in vivo . A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3' UTR of MDR1. The clonogenic assay showed that Cur enhanced the radiosensitivity of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo , resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a radiosensitizing effect on NPC cells in vivo and in vitro ; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote radiosensitivity of NPC cells.
Curli Temper Adherence of Escherichia coli O157:H7 to Squamous Epithelial Cells from the Bovine Recto-Anal Junction in a Strain-Dependent Manner

PubMed Central

Carter, Michelle Q.; Sharma, Vijay K.; Stasko, Judith A.; Giron, Jorge A.

2016-01-01

ABSTRACT Our recent studies have shown that intimin and the locus of enterocyte effacement-encoded proteins do not play a role in Escherichia coli O157:H7 (O157) adherence to the bovine recto-anal junction squamous epithelial (RSE) cells. To define factors that play a contributory role, we investigated the role of curli, fimbrial adhesins commonly implicated in adherence to various fomites and plant and human epithelial cells, in O157 adherence to RSE cells. Specifically, we examined (i) wild-type strains of O157; (ii) curli variants of O157 strains; (iii) isogenic curli deletion mutants of O157; and (iv) adherence inhibition of O157 using anti-curlin sera. Results of these experiments conducted under stringent conditions suggest that curli do not solely contribute to O157 adherence to RSE cells and in fact demonstrate a modulating effect on O157 adherence to RSE cells in contrast to HEp-2 cells (human epidermoid carcinoma of the larynx cells with HeLa contamination). The absence of curli and presence of blocking anti-curli antibodies enhanced O157-RSE cell interactions among some strains, thus alluding to a spatial, tempering effect of curli on O157 adherence to RSE cells when present. At the same time, the presence or absence of curli did not alter RSE cell adherence patterns of another O157 strain. These observations are at variance with the reported role of curli in O157 adherence to human cell lines such as HEp-2 and need to be factored in when developing anti-adherence modalities for preharvest control of O157 in cattle. IMPORTANCE This study demonstrated that O157 strains interact with epithelial cells in a host-specific manner. The fimbriae/adhesins that are significant for adherence to human cell lines may not have a role or may have a modulating role in O157 adherence to bovine cells. Targeting such adhesins may not prevent O157 attachment to bovine cells but instead may result in improved adherence. Hence, conducting host-specific evaluations is critical when selecting targets for O157 control strategies. PMID:27742683
"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

PubMed

Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

2017-10-01

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.
Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

PubMed

Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

2016-01-01

The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.
Curcumin-sensitized TiO2 for enhanced photodegradation of dyes under visible light

NASA Astrophysics Data System (ADS)

Buddee, Supat; Wongnawa, Sumpun; Sriprang, Pimpaporn; Sriwong, Chaval

2014-04-01

Curcumin was coated on P25 TiO2 by using impregnation method from freshly prepared curcumin solution. The resulting products (Cur-TiO2-P25) was studied by several techniques such as X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier-transformed infrared spectroscopy, specific surface area by the Brunauer-Emmett-Teller method, and UV-Vis diffused reflectance spectroscopy. Experimental results revealed that impregnation of curcumin at 0.5, 3, 5, and 7 wt% did not affect the native phase of anatase and rutile in P25 significantly, however, it caused red shift of absorption onset in all curcumin-coated samples. The Cur-TiO2-P25 showed enhanced adsorption efficiency and increased photocatalytic activity under visible light with optimal result at 5 wt% curcumin content. Commercial anatase and rutile coated with curcumin (Cur-TiO2-an and Cur-TiO2-ru) were also prepared by the same method for the use in comparative studies of photodegradation of dyes. Cur-TiO2-an and Cur-TiO2-ru were also characterized with some selected equipment above but not as extensively as the Cur-TiO2-P25. Curcumin coating helped improve photocatalytic efficiencies of P25 and anatase but not for rutile. The mechanism of photocatalytic reaction was proposed that under visible light irradiation, curcumin molecule could act as dye sensitizing agent that injected electron into the conduction band of TiO2 leading to photodegradation of dyes.
Curli fimbriae are conditionally required in Escherichia coli O157:H7 for initial attachment and biofilm formation.

PubMed

Carter, Michelle Qiu; Louie, Jacqueline W; Feng, Doris; Zhong, Wayne; Brandl, Maria T

2016-08-01

Several species of enteric pathogens produce curli fimbriae, which may affect their interaction with surfaces and other microbes in nonhost environments. Here we used two Escherichia coli O157:H7 outbreak strains with distinct genotypes to understand the role of curli in surface attachment and biofilm formation in several systems relevant to fresh produce production and processing. Curli significantly enhanced the initial attachment of E. coli O157:H7 to spinach leaves and stainless steel surfaces by 5-fold. Curli was also required for E. coli O157:H7 biofilm formation on stainless steel and enhanced biofilm production on glass by 19-27 fold in LB no-salt broth. However, this contribution was not observed when cells were grown in sterile spinach lysates. Furthermore, both strains of E. coli O157:H7 produced minimal biofilms on polypropylene in LB no-salt broth but considerable amounts in spinach lysates. Under the latter conditions, curli appeared to slightly increase biofilm production. Importantly, curli played an essential role in the formation of mixed biofilm by E. coli O157:H7 and plant-associated microorganisms in spinach leaf washes, as revealed by confocal microscopy. Little or no E. coli O157:H7 biofilms were detected at 4 °C, supporting the importance of temperature control in postharvest and produce processing environments. Published by Elsevier Ltd.
Characteristics and Expression Profile of KRT71 Screened by Suppression Subtractive Hybridization cDNA Library in Curly Fleece Chinese Tan Sheep.

PubMed

Kang, Xiaolong; Liu, Yufang; Zhang, Jibin; Xu, Qinqin; Liu, Chengkun; Fang, Meiying

2017-07-01

As an important commercial trait for sheep, curly fleece has a great economic impact on production costs and efficiency in sheep industry. To identify genes that are important for curly fleece formation in mammals, a suppression subtractive hybridization analysis was performed on the shoulder skin tissues exposed to two different growth stages of Chinese Tan sheep with different phenotypes (curly fleece and noncurling fleece). BLAST analysis identified 67 differentially expressed genes, of which 31 were expressed lower and 36 were expressed higher in lambs than in adult sheep. Differential expressions of seven randomly selected genes were verified using quantitative real-time polymerase chain reaction (qRT-PCR). KRT71 gene was selected for further study due to its high correlation with the curly hair phenotype in various mammal species. Semi-qPCR showed distinctively high expression of KRT71 in skin tissues. Moreover, qPCR result showed a significantly higher expression of KRT71 in curly fleece than noncurling Tan sheep. The luciferase assay and electrophoresis mobility shift assay showed that there were transcription factor binding sites in the promoter region of KRT71 related to the differential expression of KRT71 at the two growth stages of Tan sheep. Online bioinformation tools predicted MFZ1 as a transcriptional factor that regulates the expression of KRT71. These studies on KRT71 gene revealed some mechanisms underlying the relationship between the KRT71 gene and the curly fleece phenotype of Tan sheep.
Suppressing the cytotoxicity of CuO nanoparticles by uptake of curcumin/BSA particles

NASA Astrophysics Data System (ADS)

Zhang, Wenjing; Jiang, Pengfei; Chen, Ying; Luo, Peihua; Li, Guanqun; Zheng, Botuo; Chen, Wei; Mao, Zhengwei; Gao, Changyou

2016-05-01

The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu2+ concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology.
Protective effect of curcumin against ultraviolet A irradiation‑induced photoaging in human dermal fibroblasts.

PubMed

Liu, Xiaoming; Zhang, Ruizhi; Shi, Haixia; Li, Xiaobo; Li, Yanhong; Taha, Ahmad; Xu, Chunxing

2018-05-01

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor‑β (TGF‑β) and Smad2/3, and decreasing the expression of the TGF‑β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA‑induced photoaging and highlight the potential for the application of Cur in skin photoprotection.
Protective effect of curcumin against ultraviolet A irradiation-induced photoaging in human dermal fibroblasts

PubMed Central

Liu, Xiaoming; Zhang, Ruizhi; Shi, Haixia; Li, Xiaobo; Li, Yanhong; Taha, Ahmad; Xu, Chunxing

2018-01-01

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)-induced photoaging. HDFs were treated with 0–10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2′,7′-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA-induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose-regulated protein 78, C/EBP-homologous protein, nuclear factor-κB and cleaved caspase-3, while upregulating the expression of Bcl-2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)-1 and MMP-3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor-β (TGF-β) and Smad2/3, and decreasing the expression of the TGF-β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA-induced photoaging and highlight the potential for the application of Cur in skin photoprotection. PMID:29568864
Curcumin-loaded dual pH- and thermo-responsive magnetic microcarriers based on pectin maleate for drug delivery.

PubMed

Almeida, Elizângela A M S; Bellettini, Ismael C; Garcia, Francielle P; Farinácio, Maroanne T; Nakamura, Celso V; Rubira, Adley F; Martins, Alessandro F; Muniz, Edvani C

2017-09-01

Magnetic microgels with pH- and thermo-responsive properties were developed from the pectin maleate, N-isopropyl acrylamide, and Fe 3 O 4 nanoparticles. The hybrid materials were characterized by infrared spectroscopy, scanning electron microscope coupled with X-ray energy dispersive spectroscopy, wide angle X-ray scattering, Zeta potential, and magnetization hysteresis measurements. Curcumin (CUR) was loaded into the microgels, and release assays were carried out in simulated environments (SGF and SIF) at different conditions of temperature (25 or 37°C). A slow and sustainability CUR release was achieved under external magnetic field influence. Loaded CUR displayed stability, bioavailability and greater solubility regarding free CUR. Besides, the cytotoxicity assays showed that magnetic microgels without CUR could suppress the Caco-2 cells growth. So, the pectin maleate, N-isopropyl acrylamide, and Fe 3 O 4 could be tailored to elicit hybrid-based materials with satisfactory application in the medical arena. Copyright © 2017 Elsevier Ltd. All rights reserved.
Synthesis and characterization of curcumin loaded PLA-Hyperbranched polyglycerol electrospun blend for wound dressing applications.

PubMed

Perumal, Govindaraj; Pappuru, Sreenath; Chakraborty, Debashis; Maya Nandkumar, A; Chand, Dillip Kumar; Doble, Mukesh

2017-07-01

This study is aimed to develop curcumin (Cur) incorporated electrospun nanofibers of a blend of poly (lactic acid) (PLA) and hyperbranched polyglycerol (HPG) for wound healing applications. Both the polymers are synthesized and fabricated by electrospinning technique. The produced nanofibers were characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Colorimetry (DSC) and Thermogravimetric Analysis (TGA). Electrospun scaffolds (PLA/HPG/Cur) exhibits very high hydrophilicity, high swelling and drug uptake and promotes better cell viability, adhesion and proliferation when compared to PLA/Cur electrospun nanofibers. Biodegradation study revealed that the morphology of the nanofibers were unaffected even after 14days immersion in Phosphate Buffered Saline. In vitro scratch assay indicates that migration of the cells in the scratch treated with PLA/HPG/Cur is complete within 36h. These results suggest that PLA/HPG/Cur nanofibers can be a potential wound patch dressing for acute and chronic wound applications. Copyright © 2017 Elsevier B.V. All rights reserved.
Greening Industrial Production through Waste Recovery: "Comprehensive Utilization of Resources" in China.

PubMed

Zhu, Junming; Chertow, Marian R

2016-03-01

Using nonhazardous wastes as inputs to production creates environmental benefits by avoiding disposal impacts, mitigating manufacturing impacts, and conserving virgin resources. China has incentivized reuse since the 1980s through the "Comprehensive Utilization of Resources (CUR)" policy. To test whether and to what extent environmental benefits are generated, 862 instances in Jiangsu, China are analyzed, representing eight industrial sectors and 25 products that qualified for tax relief through CUR. Benefits are determined by comparing life cycle inventories for the same product from baseline and CUR-certified production, adjusted for any difference in the use phase. More than 50 million tonnes of solid wastes were reused, equivalent to 51% of the provincial industrial total. Benefits included reduction of 161 petajoules of energy, 23 million tonnes of CO2 equivalent, 75 000 tonnes of SO2 equivalent, 33 000 tonnes of NOX, and 28 000 tonnes of PM10 equivalent, which were 2.5%-7.3% of the provincial industrial consumption and emissions. The benefits vary substantially across industries, among products within the same industry, and when comparing alternative reuse processes for the same waste. This first assessment of CUR results shows that CUR has established a firm foundation for a circular economy, but also suggest additional opportunities to refine incentives under CUR to increase environmental gain.
An Intestinal "Transformers"-like Nanocarrier System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs.

PubMed

Chuang, Er-Yuan; Lin, Kun-Ju; Huang, Tring-Yo; Chen, Hsin-Lung; Miao, Yang-Bao; Lin, Po-Yen; Chen, Chiung-Tong; Juang, Jyuhn-Huarng; Sung, Hsing-Wen

2018-06-06

Increasing the intestinal dissolution of orally administered poorly water-soluble drugs that have poor oral bioavailability to a therapeutically effective level has long been an elusive goal. In this work, an approach that can greatly enhance the oral bioavailability of a poorly water-soluble drug such as curcumin (CUR) is developed, using a "Transformers"-like nanocarrier system (TLNS) that can self-emulsify the drug molecules in the intestinal lumen to form nanoemulsions. Owing to its known anti-inflammation activity, the use of CUR in treating pancreatitis is evaluated herein. Structural changes of the TLNS in the intestinal environment to form the CUR-laden nanoemulsions are confirmed in vitro. The therapeutic efficacy of this TLNS is evaluated in rats with experimentally induced acute pancreatitis (AP). Notably, the CUR-laden nanoemulsions that are obtained using the proposed TLNS can passively target intestinal M cells, in which they are transcytosed and then transported into the pancreatic tissues via the intestinal lymphatic system. The pancreases in rats that are treated with the TLNS yield approximately 12 times stronger CUR signals than their counterparts receiving free CUR, potentially improving the recovery of AP. These findings demonstrate that the proposed TLNS can markedly increase the intestinal drug dissolution, making oral delivery a favorable noninvasive means of administering poorly water-soluble drugs.

Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.

PubMed

Duan, Yuwei; Zhang, Baomei; Chu, Lianjun; Tong, Henry Hy; Liu, Weidong; Zhai, Guangxi

2016-05-01

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.
Formulation of curcumin delivery with functionalized single-walled carbon nanotubes: characteristics and anticancer effects in vitro.

PubMed

Li, Haixia; Zhang, Nan; Hao, Yongwei; Wang, Yali; Jia, Shasha; Zhang, Hongling; Zhang, Yun; Zhang, Zhenzhong

2014-08-01

Single-walled carbon nanotubes (SWCNTs), an important class of artificial nanomaterials with unique physicochemical properties, were used as novel carriers of curcumin. Formulation and evaluation of curcumin-loaded SWCNTs systems for utilizing the curcumin's anticancer potential by circumventing conventional limitations of extremely low aqueous solubility and instability under physiological conditions, and combining SWCNTs photothermal therapy enabled by the strong optical absorbance of SWCNTs in the 0.8-1.4 μm resulting in excessive local heating. After functionalized SWCNTs were confirmed, they were conjugated with curcumin (SWCNT-Cur). Subsequently, the formulation was analyzed for size, zeta-potential and morphology. And the solubility, stability and release of curcumin were assessed using spectrofluorometer, and the solid state of the curcumin was determined using X-ray diffraction and UV spectroscopy. Furthermore, in PC-3 cells, photothermal response was further determined by irradiating laser after the antitumor effect of SWCNT-Cur was evaluated. SWCNTs were functionalized, and subsequent SWCNT-Cur conjugates were found to possess an average size of 170.4 nm, a zeta potential of -12.5 mV and to significantly enhance the solubility and stability of curcumin, overcoming the barriers to adequate curcumin delivery. Moreover, curcumin in SWCNT-Cur was in an amorphous form and could be rapidly released. In PC-3 cells, improved inhibition efficacy was achieved by SWCNT-Cur compared with native curcumin. Meanwhile, the SWCNTs in SWCNT-Cur served not only as scaffolds but also as thermal ablation agents, further inhibiting PC-3 cell growth. SWCNT-Cur assemblies may provide a promising delivery system for curcumin for use in cancer therapy.
Photo-induced green synthesis and antimicrobial efficacy of poly (ɛ-caprolactone)/curcumin/grape leaf extract-silver hybrid nanoparticles.

PubMed

El-Sherbiny, Ibrahim M; El-Shibiny, Ayman; Salih, Ehab

2016-07-01

This study reports the photo-induced green synthesis and antimicrobial assessment of poly(ɛ-caprolactone)/curcumin/grape leaf extract-Ag hybrid nanoparticles (PCL/Cur/GLE-Ag NPs). PCL/Cur/GLE NPs were synthesized via emulsion-solvent evaporation in the presence of PVA as a capping agent, then used as active nano-supports for the green synthesis and stabilization of AgNPs on their surfaces. Both Cur and GLE were selected and incorporated into the PCL nano-supports due to their reported promising antimicrobial activity that would further enhance that of the synthesized AgNPs. The developed PCL/Cur/GLE NPs and PCL/Cur/GLE-Ag hybrid NPs were characterized using UV-visible spectrophotometry, high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). HRTEM images showed that the PCL/Cur/GLE NPs are monodispersed and spherical with size of about 270nm, and the AgNPs were formed mainly on their surfaces with average size in the range 10-30nm. The synthesized AgNPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220) and (311) planes. The antimicrobial characteristics of the newly developed NPs were investigated against gram-positive and gram-negative bacteria in addition to two fungal strains. The results demonstrated that the PCL/Cur/GLE-Ag hybrid NPs have a potential antimicrobial activity against pathogenic bacterial species and could be considered as an alternative antibacterial agent. Copyright © 2016 Elsevier B.V. All rights reserved.
Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans.

PubMed

Krustrup, Peter; Secher, Niels H; Relu, Mihai U; Hellsten, Ylva; Söderlund, Karin; Bangsbo, Jens

2008-12-15

We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P < 0.05) by 28% in FT fibres, whereas in CON, CP decreased (P < 0.05) by 33% and 23% in ST and FT fibres, respectively. From 127 s of exercise, muscle VO2 was higher (P < 0.05) in CUR compared to CON (425 +/- 25 (+/- S.E.M.) versus 332 +/- 30 ml min(-1)) and remained higher (P < 0.05) throughout exercise. Using monoexponential fitting, the time constant of the exercise-induced muscle VO2 response was slower (P < 0.05) in CUR than in CON (55 +/- 6 versus 33 +/- 5 s). During CUR and CON, muscle homogenate CP was lowered (P < 0.05) by 32 and 35%, respectively, and also muscle lactate production was similar in CUR and CON (37.8 +/- 4.1 versus 35.2 +/- 6.2 mmol). Estimated total muscle ATP turnover was 19% higher (P < 0.05) in CUR than in CON (1196 +/- 90 versus 1011 +/- 59 mmol) and true mechanical efficiency was lower (P < 0.05) in CUR than in CON (26.2 +/- 2.0 versus 30.9 +/- 1.5%). In conclusion, the present findings provide evidence that FT fibres are less efficient than ST fibres in vivo at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation.
Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin.

PubMed

Fatima, Munazza T; Chanchal, Abhishek; Yavvari, Prabhu S; Bhagat, Somnath D; Gujrati, Mansi; Mishra, Ram K; Srivastava, Aasheesh

2016-07-11

Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their death by apoptosis. Noncancerous cells were completely unaffected under this treatment.
Synergistic effects of thymoquinone and curcumin on immune response and anti-viral activity against avian influenza virus (H9N2) in turkeys.

PubMed

Umar, S; Shah, M A A; Munir, M T; Yaqoob, M; Fiaz, M; Anjum, S; Kaboudi, K; Bouzouaia, M; Younus, M; Nisa, Q; Iqbal, M; Umar, W

2016-07-01

The main objective of this study was to determine the possible effects of thymoquinone (TQ) and curcumin (Cur) on immune-response and pathogenesis of H9N2 avian influenza virus (AIV) in turkeys. The experiment was performed on 75 non-vaccinated mixed-sex turkey poults, divided into 5 experimental groups (A, B, C, D, and E) of 15 birds each. Group A was kept as non-infected and a non-treated negative control (ctrl group) while group B was kept as infected and non-treated positive control (H9N2 group). Turkeys in groups A and B received normal commercial feed while turkeys in groups C and D received TQ, and Cur respectively, and group E concurrently received TQ and Cur from d one through the entire experiment period. All groups were challenged intra-nasally with H9N2 AIV (A/chicken/Pakistan/10RS3039-284-48/2010) at the fourth wk of age except group A. Infected turkeys showed clinical signs of different severity, showing the most prominent disease signs in turkeys in group B. All infected turkeys showed positive results for virus shedding; however, the pattern of virus shedding was different, and with turkeys in group B showing more pronounced virus secretion than the turkeys in the other groups receiving different levels of TQ and Cur. Moreover, significantly higher antibody titer against H9N2 AIV in turkeys shows the immunomodulatory nature of TQ and Cur. Similarly, increased cytokine gene expression suggests antiviral behavior of TQ and Cur especially in combination, leading to suppressed pathogenesis of H9N2 viruses. However, reduced virus shedding and enhanced immune responses were more pronounced in those turkeys receiving TQ and Cur concurrently. This study showed that supplements of TQ and Cur in combination would significantly enhance immune responsiveness and suppress pathogenicity of influenza viruses in turkeys. © 2016 Poultry Science Association Inc.
Inquiry-Based Learning in an Intermediate-Level Undergraduate Neotectonics Course

NASA Astrophysics Data System (ADS)

Reinen, L. A.

2007-12-01

Integrating student-conducted research into the curriculum can provide students with many educational benefits. Documented benefits include, among others, increased communication skills, the ability to work as part of a research team, and enhanced self-confidence in individual problem-solving skills (e.g., Kardash, J. Ed. Psych., 2000; Seymour, et al., Science Education, 2004). As part of a larger departmental goal of integrating student- conducted research into all levels of the Pomona College Geology Department curriculum (e.g., Reinen, et al., CUR-Q, 2006), I have recently developed an intermediate-level Neotectonics course with a strong component of inquiry-based learning. This course was offered for the first time during the spring semester 2007, and will continue to be offered each year. In a series of guided inquiries throughout the course, students investigate recent seismicity and tectonic geomorphology in Southern California. With each subsequent assignment, student contributions to the research direction increases (e.g., data used, area studied, question addressed, methods used), culminating in team proposals and research projects investigating specific student-generated questions of regional tectonics. Students collect data for these investigations from several sources: (1) databases available online (e.g., IRIS, Harvard earthquake catalog), (2) desktop experiments (e.g., the "earthquake machine"), (3) topographic maps, and (4) field observations. The objective of this paper is to present initial results from this teaching experiment and examples of the projects which have been executed, including the preparation students received to be able to use the available data. Discussion and suggestions (particularly about effective means of conducting a rigorous long-term assessment) are strongly encouraged.
A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer's disease mice.

PubMed

Maiti, Panchanan; Hall, Tia C; Paladugu, Leela; Kolli, Nivya; Learman, Cameron; Rossignol, Julien; Dunbar, Gary L

2016-11-01

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.
Transport of curcumin derivatives in Caco-2 cell monolayers.

PubMed

Zeng, Zhen; Shen, Zhe L; Zhai, Shuo; Xu, Jia L; Liang, Hui; Shen, Qin; Li, Qing Y

2017-08-01

Curcumin (Cur) is a strong natural antioxidant, who can prevent multiple diseases such as anti-cancer, anti-inflammatory, have a resistance to alzheimer's disease and various malignant diseases. But it has poor oral bioavailability due to its poor aqueous solubility, as well as instability. While its novel derivatives (CB and FE), showed better anti-tumor activity, better anti-oxidant activity and better stability than the original drug (Cur). The aim of this study was to study the intestinal transport of Cur, CB and FE using an in vitro Caco-2 cell monolayer model. The results showed that Cur had a lower permeability coefficient (1.13×10 -6 ±0.11×10 -6 cm/s) for apical-to-basolated (AP-BL) transport at 25μM, while the transport rate for AP to BL flux of CB (3.18×10 -6 ±0.31×10 -6 cm/s) and FE (5.28×10 -6 ±0.83×10 -6 cm/s) were significantly greater than that of Cur. The efflux ratio (ER) value at the concentration of 25μM was 1.31 for Cur, 1.26 for CB and 1.33 for FE, suggesting there was no active efflux involved in the translocation across the Caco-2 cell monolayers for the three compounds. Furthermore, the transport flux of CB and FE was in a concentration dependent manner, suggesting the intestinal transport mechanism in them was passive transport. In summary, the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved compare to Cur. Thus they might show a higher oral bioavailability in vivo, and show the potential application in clinic or nutraceutical. Copyright © 2017 Elsevier B.V. All rights reserved.
Combination of tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species.

PubMed

Sankpal, Umesh T; Nagaraju, Ganji Purnachandra; Gottipolu, Sriharika R; Hurtado, Myrna; Jordan, Christopher G; Simecka, Jerry W; Shoji, Mamoru; El-Rayes, Bassel; Basha, Riyaz

2016-01-19

Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24-72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/ time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells.
Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1.

PubMed

Guo, Yue; Shu, Limin; Zhang, Chengyue; Su, Zheng-Yuan; Kong, Ah-Ng Tony

2015-03-15

Colorectal cancer remains the most prevalent malignancy in humans. The impact of epigenetic alterations on the development of this complex disease is now being recognized. The dynamic and reversible nature of epigenetic modifications makes them a promising target in colorectal cancer chemoprevention and treatment. Curcumin (CUR), the major component in Curcuma longa, has been shown as a potent chemopreventive phytochemical that modulates various signaling pathways. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene with reduced transcriptional activity and promoter hypermethylation in various cancers, including colorectal cancer. In the present study, we aimed to investigate the inhibitory role of DLEC1 in anchorage-independent growth of the human colorectal adenocarcinoma HT29 cells and epigenetic regulation by CUR. Specifically, we found that CUR treatment inhibited colony formation of HT29 cells, whereas stable knockdown of DLEC1 using lentiviral short hairpin RNA vector increased cell proliferation and colony formation. Knockdown of DLEC1 in HT29 cells attenuated the ability of CUR to inhibit anchorage-independent growth. Methylation-specific polymerase chain reaction (MSP), bisulfite genomic sequencing, and methylated DNA immunoprecipitation revealed that CUR decreased CpG methylation of the DLEC1 promoter in HT29 cells after 5 days of treatment, corresponding to increased mRNA expression of DLEC1. Furthermore, CUR decreased the protein expression of DNA methyltransferases and subtypes of histone deacetylases (HDAC4, 5, 6, and 8). Taken together, our results suggest that the inhibitory effect of CUR on anchorage-independent growth of HT29 cells could, at least in part, involve the epigenetic demethylation and up-regulation of DLEC1. Copyright © 2015 Elsevier Inc. All rights reserved.
Characterization of the Biosynthetic Genes for 10,11-Dehydrocurvularin, a Heat Shock Response-Modulating Anticancer Fungal Polyketide from Aspergillus terreus

PubMed Central

Xu, Yuquan; Espinosa-Artiles, Patricia; Schubert, Vivien; Xu, Ya-ming; Zhang, Wei; Lin, Min; Gunatilaka, A. A. Leslie; Süssmuth, Roderich

2013-01-01

10,11-Dehydrocurvularin is a prevalent fungal phytotoxin with heat shock response and immune-modulatory activities. It features a dihydroxyphenylacetic acid lactone polyketide framework with structural similarities to resorcylic acid lactones like radicicol or zearalenone. A genomic locus was identified from the dehydrocurvularin producer strain Aspergillus terreus AH-02-30-F7 to reveal genes encoding a pair of iterative polyketide synthases (A. terreus CURS1 [AtCURS1] and AtCURS2) that are predicted to collaborate in the biosynthesis of 10,11-dehydrocurvularin. Additional genes in this locus encode putative proteins that may be involved in the export of the compound from the cell and in the transcriptional regulation of the cluster. 10,11-Dehydrocurvularin biosynthesis was reconstituted in Saccharomyces cerevisiae by heterologous expression of the polyketide synthases. Bioinformatic analysis of the highly reducing polyketide synthase AtCURS1 and the nonreducing polyketide synthase AtCURS2 highlights crucial biosynthetic programming differences compared to similar synthases involved in resorcylic acid lactone biosynthesis. These differences lead to the synthesis of a predicted tetraketide starter unit that forms part of the 12-membered lactone ring of dehydrocurvularin, as opposed to the penta- or hexaketide starters in the 14-membered rings of resorcylic acid lactones. Tetraketide N-acetylcysteamine thioester analogues of the starter unit were shown to support the biosynthesis of dehydrocurvularin and its analogues, with yeast expressing AtCURS2 alone. Differential programming of the product template domain of the nonreducing polyketide synthase AtCURS2 results in an aldol condensation with a different regiospecificity than that of resorcylic acid lactones, yielding the dihydroxyphenylacetic acid scaffold characterized by an S-type cyclization pattern atypical for fungal polyketides. PMID:23335766
Electrostatic lipid-protein interactions sequester the curli amyloid fold on the lipopolysaccharide membrane surface.

PubMed

Swasthi, Hema M; Mukhopadhyay, Samrat

2017-12-01

Curli is a functional amyloid protein in the extracellular matrix of enteric Gram-negative bacteria. Curli is assembled at the cell surface and consists of CsgA, the major subunit of curli, and a membrane-associated nucleator protein, CsgB. Oligomeric intermediates that accumulate during the lag phase of amyloidogenesis are generally toxic, but the underlying mechanism by which bacterial cells overcome this toxicity during curli assembly at the surface remains elusive. Here, we elucidated the mechanism of curli amyloidogenesis and provide molecular insights into the strategy by which bacteria can potentially bypass the detrimental consequences of toxic amyloid intermediates. Using a diverse range of biochemical and biophysical tools involving circular dichroism, fluorescence, Raman spectroscopy, and atomic force microscopy imaging, we characterized the molecular basis of the interaction of CsgB with a membrane-mimetic anionic surfactant as well as with lipopolysaccharide (LPS) constituting the outer leaflet of Gram-negative bacteria. Aggregation studies revealed that the electrostatic interaction of the positively charged C-terminal region of the protein with a negatively charged head group of surfactant/LPS promotes a protein-protein interaction that results in facile amyloid formation without a detectable lag phase. We also show that CsgB, in the presence of surfactant/LPS, accelerates the fibrillation rate of CsgA by circumventing the lag phase during nucleation. Our findings suggest that the electrostatic interactions between lipid and protein molecules play a pivotal role in efficiently sequestering the amyloid fold of curli on the membrane surface without significant accumulation of toxic oligomeric intermediates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Neuronal Uptake and Neuroprotective Properties of Curcumin-Loaded Nanoparticles on SK-N-SH Cell Line: Role of Poly(lactide-co-glycolide) Polymeric Matrix Composition.

PubMed

Djiokeng Paka, Ghislain; Doggui, Sihem; Zaghmi, Ahlem; Safar, Ramia; Dao, Lé; Reisch, Andreas; Klymchenko, Andrey; Roullin, V Gaëlle; Joubert, Olivier; Ramassamy, Charles

2016-02-01

Curcumin, a neuroprotective agent with promising therapeutic approach has poor brain bioavailability. Herein, we demonstrate that curcumin-encapsulated poly(lactide-co-glycolide) (PLGA) 50:50 nanoparticles (NPs-Cur 50:50) are able to prevent the phosphorylation of Akt and Tau proteins in SK-N-SH cells induced by H2O2 and display higher anti-inflammatory and antioxidant activities than free curcumin. PLGA can display various physicochemical and degradation characteristics for controlled drug release applications according to the matrix used. We demonstrate that the release of curcumin entrapped into a PLGA 50:50 matrix (NPs-Cur 50:50) is faster than into PLGA 65:35. We have studied the effects of the PLGA matrix on the expression of some key antioxidant- and neuroprotective-related genes such as APOE, APOJ, TRX, GLRX, and REST. NPs-Cur induced the elevation of GLRX and TRX while decreasing APOJ mRNA levels and had no effect on APOE and REST expressions. In the presence of H2O2, both NPs-Cur matrices are more efficient than free curcumin to prevent the induction of these genes. Higher uptake was found with NPs-Cur 50:50 than NPs-Cur 65:35 or free curcumin. By using PLGA nanoparticles loaded with the fluorescent dye Lumogen Red, we demonstrated that PLGA nanoparticles are indeed taken up by neuronal cells. These data highlight the importance of polymer composition in the therapeutic properties of the nanodrug delivery systems. Our study demonstrated that NPs-Cur enhance the action of curcumin on several pathways implicated in the pathophysiology of Alzheimer's disease (AD). Overall, these results suggest that PLGA nanoparticles are a promising strategy for the brain delivery of drugs for the treatment of AD.
Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line.

PubMed

Doggui, Sihem; Sahni, Jasjeet Kaur; Arseneault, Madeleine; Dao, Lé; Ramassamy, Charles

2012-01-01

Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-β activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease.
Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation.

PubMed

Shu, Qin; Krezel, Andrzej M; Cusumano, Zachary T; Pinkner, Jerome S; Klein, Roger; Hultgren, Scott J; Frieden, Carl

2016-06-28

Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface of Escherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. CsgE binds to both CsgA and the nonameric pore protein CsgG. The CsgG-CsgE complex is the curli secretion channel and is essential for the formation of the curli fibril in vivo. To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. The well-converged structure of this mutant has a core scaffold composed of a layer of two α-helices and a layer of three-stranded antiparallel β-sheet with flexible N and C termini. The structure of CsgE fits well into the cryoelectron microscopy density map of the CsgG-CsgE complex. We highlight a striking feature of the electrostatic potential surface in CsgE structure and present an assembly model of the CsgG-CsgE complex. We suggest a structural mechanism of the interaction between CsgE and CsgA. Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. CsgE could establish a paradigm for the regulation of amyloidogenesis because of its unique role in curli formation.
The association between a low cerebro-umbilical ratio at 30-34 weeks gestation, increased intrapartum operative intervention and adverse perinatal outcomes.

PubMed

Twomey, Sarah; Flatley, Christopher; Kumar, Sailesh

2016-08-01

The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes. This was a retrospective cross-sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study. Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR ≤1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR >1 (adjusted OR 6.92 (95% CI 2.04-25.75), p<0.001). However, the detection rate of CUR ≤1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights <10th centile or <5th centile. Additionally, a CUR ≤1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality. This study suggests that a CUR ≤1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies. Copyright © 2016. Published by Elsevier Ireland Ltd.
Differential expression of CURS gene during various growth stages, climatic condition and soil nutrients in turmeric (Curcuma longa): Towards site specific cultivation for high curcumin yield.

PubMed

Sandeep, I Sriram; Das, Suryasnata; Nasim, Noohi; Mishra, Antaryami; Acharya, Laxmikanta; Joshi, Raj Kumar; Nayak, Sanghamitra; Mohanty, Sujata

2017-09-01

Curcuma longa L., accumulates substantial amount of curcumin and essential oil. Little is known about the differential expression of curcumin synthase (CURS) gene and consequent curcumin content variations at different agroclimatic zones. The present study aimed to evaluate the effect of climate, soil and harvesting phase on expression of CURS gene for curcumin yield in two high yielding turmeric cultivars. Expression of CURS gene at different experimental zones as well as at different harvesting phase was studied through transcriptional analysis by qRT-PCR. Curcumin varied from 1.5 to 5% and 1.4-5% in Surama and Roma respectively. The expression of CURS also varied from 0.402 to 5.584 fold in Surama and 0.856-5.217 fold in Roma. Difference in curcumin content at a particular zone varied among different harvesting period from 3.95 to 4.31% in Surama and 3.57-3.83% in Roma. Expression of CURS gene was also effected by harvesting time of the rhizome which varied from 7.389 to 16.882 fold in Surama and 4.41-8.342 fold in Roma. The CURS gene expression was found regardless of variations in curcumin content at different experimental zones. This may be due to the effects of soil and environmental variables. Expression was positively correlated with curcumin content with different harvesting time at a particular zone. This find indicates effect of soil and environment on molecular and biochemical dynamics of curcumin biosynthesis and could be useful in genetic improvement of turmeric. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Protective effects and mechanisms of curcumin on podophyllotoxin toxicity in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Juan; Dai, Cai-Xia; Sun, Hua

2012-12-01

Podophyllotoxin (POD) is a naturally occurring lignan with pronounced antineoplastic and antiviral properties. POD binds to tubulin and prevents the formation of mitotic spindle. Although cases of overdose or accidental ingestion are quite often, no specific therapy is currently available to treat the POD intoxication. In the current investigation, the protective effects and mechanisms of curcumin (CUR) on podophyllotoxin toxicity were evaluated in vitro and in vivo. The results showed that CUR could protect POD-induced cytotoxicity by recovering the G2/M arrest and decrease the changes of membrane potential and microtubule structure in Vero cells. A significant decrease of mortality ratesmore » was observed in Swiss mice treated by intragastrical administration of POD + CUR as compared with POD alone. The POD + CUR group also exhibited decreases in plasma transaminases, alkaline phosphatase, lactate dehydrogenase, plasma urea, creatinine and malondialdehyde level but elevated superoxide dismutase and glutathione levels as compared to the POD group. Histological examination of the liver and kidney demonstrated less morphological changes in the treatment of POD + CUR as compared with POD alone. The mechanism of the protective effects might be due to the competitive binding of CUR with POD in the same colchicines binding site as revealed by the tubulin polymerization assay and the molecular docking analysis, and the antioxidant activity against the oxidative stress induced by POD. In summary, both in vitro and in vivo data indicated the promising role of CUR as a protective agent against the POD poisoning. Highlights: ► A potential antidote to treat the podophyllotoxin (POD) intoxication is found. ► Curcumin showed promising effects against POD poisoning in vitro and in vivo. ► The mechanisms lie in the antioxidant activity and competitive binding with tubulin.« less
Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells

PubMed Central

Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (−)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2–4 mg/L (about 5–10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer. PMID:25243063

Breast Cancer-Targeted Nuclear Drug Delivery Overcoming Drug Resistance for Breast Cancer Chemotherapy

DTIC Science & Technology

2010-09-01

compared with the reported results that the cur- cumin concentrations in tumor tissues were usu- ally very low when curcumin was administrated. The...prodrug and as a drug carrier. This cur- cumin prodrug has a fixed composition with a curcumin-loading content of 25.3 wt% and can release curcumin...200 or 400, Aldrich, 99%) was dried over calcium hydride. Cur- cumin (high purity, Axxora LLC) was further purified by repeated recrystallization in
Curli Fibers Are Highly Conserved between Salmonella typhimurium and Escherichia coli with Respect to Operon Structure and Regulation

PubMed Central

Römling, Ute; Bian, Zhao; Hammar, Mårten; Sierralta, Walter D.; Normark, Staffan

1998-01-01

Mouse-virulent Salmonella typhimurium strains SR-11 and ATCC 14028-1s express curli fibers, thin aggregative fibers, at ambient temperature on plates as judged by Western blot analysis and electron microscopy. Concomitantly with curli expression, cells develop a rough and dry colony morphology and bind the dye Congo red (called the rdar morphotype). Cloning and characterization of the two divergently transcribed operons required for curli biogenesis, csgBA(C) and csgDEFG, from S. typhimurium SR-11 revealed the same gene order and flanking genes as in Escherichia coli. The divergence of the curli region between S. typhimurium and E. coli at the nucleotide level is above average (22.4%). However, a high level of conservation at the protein level, which ranged from 86% amino acid homology for the fiber subunit CsgA to 99% homology for the lipoprotein CsgG, implies functional constraints on the gene products. Consequently, S. typhimurium genes on low-copy-number plasmids were able to complement respective E. coli mutants, although not always to wild-type levels. rpoS and ompR are required for transcriptional activation of (at least) the csgD promoter. The high degree of conservation at the protein level and the identical regulation patterns in E. coli and S. typhimurium suggest similar roles of curli fibers in the same ecological niche in the two species. PMID:9457880
Insulin catalyzes the curcumin-induced wound healing: An in vitro model for gingival repair

PubMed Central

Singh, Neetu; Ranjan, Vishal; Zaidi, Deeba; Shyam, Hari; Singh, Aparna; Lodha, Divya; Sharma, Ramesh; Verma, Umesh; Dixit, Jaya; Balapure, Anil K.

2012-01-01

Objectives: Human gingival fibroblasts (hGFs) play a major role in the maintenance and repair of gingival connective tissue. The mitogen insulin with IGFs etc. synergizes in facilitating wound repair. Although curcumin (CUR) and insulin regulate apoptosis, their impact as a combination on hGF in wound repair remains unknown. Our study consists of: 1) analysis of insulin-mediated mitogenesis on CUR-treated hGF cells, and 2) development of an in vitro model of wound healing. Materials and Methods: Apoptotic rate in CUR-treated hGF cells with and without insulin was observed by AnnexinV/PI staining, nuclear morphological analysis, FACS and DNA fragmentation studies. Using hGF confluent cultures, wounds were mechanically created in vitro and incubated with the ligands for 48 h in 0.2% fetal bovine serum DMEM. Results: CUR alone showed dose-dependent (1–50 μM) effects on hGF. Insulin (1 μg/ml) supplementation substantially enhanced cell survival through up-regulation of mitogenesis/anti-apoptotic elements. Conclusions: The in vitro model for gingival wound healing establishes that insulin significantly enhanced wound filling faster than CUR-treated hGF cells over 48 h. This reinforces the pivotal role of insulin in supporting CUR-mediated wound repair. The findings have significant bearing in metabolic dysfunctions, e.g. diabetes, atherosclerosis, etc., especially under Indian situations. PMID:23087505
Biofilm formation, cellulose production, and curli biosynthesis by Salmonella originating from produce, animal, and clinical sources.

PubMed

Solomon, Ethan B; Niemira, Brendan A; Sapers, Gerald M; Annous, Bassam A

2005-05-01

The ability of 71 strains of Salmonella enterica originating from produce, meat, or clinical sources to form biofilms was investigated. A crystal violet binding assay demonstrated no significant differences in biofilm formation by isolates from any source when tested in any of the following three media: Luria-Bertani broth supplemented with 2% glucose, tryptic soy broth (TSB), or 1/20th-strength TSB. Incubation was overnight at 30 degrees C under static conditions. Curli production and cellulose production were monitored by assessing morphotypes on Luria-Bertani agar without salt containing Congo red and by assessing fluorescence on Luria-Bertani agar containing calcofluor, respectively. One hundred percent of the clinical isolates exhibited curli biosynthesis, and 73% demonstrated cellulose production. All meat-related isolates formed curli, and 84% produced cellulose. A total of 80% of produce-related isolates produced curli, but only 52% produced cellulose. Crystal violet binding was not statistically different between isolates representing the three morphotypes when grown in TSB; however, significant differences were observed when strains were cultured in the two other media tested. These data demonstrate that the ability to form biofilms is not dependent on the source of the test isolate and suggest a relationship between crystal violet binding and morphotype, with curli- and cellulose-deficient isolates being least effective in biofilm formation.
Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis.

PubMed

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.
Lipopolysaccharide based oral nanocarriers for the improvement of bioavailability and anticancer efficacy of curcumin.

PubMed

Chaurasia, Sundeep; Patel, Ravi R; Chaubey, Pramila; Kumar, Nagendra; Khan, Gayasuddin; Mishra, Brahmeshwar

2015-10-05

Soluthin MD(®), a unique phosphatidylcholine-maltodextrin based hydrophilic lipopolysaccharide, which exhibits superior biocompatibility and bioavailability enhancer properties for poorly water soluble drug(s). Curcumin (CUR) is a potential natural anticancer drug with low bioavailability due to poor aqueous solubility. The study aims at formulation and optimization of CUR loaded lipopolysaccharide nanocarriers (C-LPNCs) to enhance oral bioavailability and anticancer efficacy in colon-26 tumor-bearing mice in vitro and in vivo. The Optimized C-LPNCs demonstrated favorable mean particle size (108 ± 3.4 nm) and percent entrapment efficiency (65.29 ± 1.0%). Pharmacokinetic parameters revealed ∼130-fold increase in oral bioavailability and cytotoxicity studies demonstrated ∼23-fold reduction in 50% cell growth inhibition when treated with optimized C-LPNCs as compared to pure CUR. In vivo anticancer study performed with optimized C-LPNCs showed significant increase in efficacy compared with pure CUR. Thus, lipopolysaccharide nanocarriers show potential delivery strategy to improve oral bioavailability and anticancer efficacy of CUR in the treatment of colorectal cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.
Enhancement of Curcumin Solubility by Phase Change from Crystalline to Amorphous in Cur-TPGS Nanosuspension.

PubMed

Shin, Gye Hwa; Li, Jinglei; Cho, Jin Hun; Kim, Jun Tae; Park, Hyun Jin

2016-02-01

Nanosuspensions (NSs) were fabricated to enhance water solubility, dissolution rate, and oral adsorption of water insoluble curcumin using sonoprecipitation method. As a good stabilizer, d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) was used to improve the stability of curcumin-TPGS NSs (Cur-TPGS NSs). Ultrasonic homogenization (UH) could effectively enhance the solubility of curcumin and to produce homogeneous NSs with small particle sizes. Water solubility of curcumin was significantly improved from 0.6 μg/mL in pure water to 260 μg/mL in the mixture of curcumin and TPGS (1:10) with UH treatment. The mean particle size of Cur-TPGS NSs was decreased significantly after UH and maintained between 208 and 246 nm. Lyophilized powder of Cur-TPGS NSs was dissolved about 91.08% whereas the pristine curcumin powder was dissolved only 6.5% at pH 7.4. This study showed a great potential of Cur-TPGS NSs as a good nano-formulation of curcumin with enhanced solubility and improved oral adsorption. © 2016 Institute of Food Technologists®
Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

PubMed Central

Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

2015-01-01

Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750
Printing of Patterned, Engineered E. coli Biofilms with a Low-Cost 3D Printer.

PubMed

Schmieden, Dominik T; Basalo Vázquez, Samantha J; Sangüesa, Héctor; van der Does, Marit; Idema, Timon; Meyer, Anne S

2018-05-18

Biofilms can grow on virtually any surface available, with impacts ranging from endangering the lives of patients to degrading unwanted water contaminants. Biofilm research is challenging due to the high degree of biofilm heterogeneity. A method for the production of standardized, reproducible, and patterned biofilm-inspired materials could be a boon for biofilm research and allow for completely new engineering applications. Here, we present such a method, combining 3D printing with genetic engineering. We prototyped a low-cost 3D printer that prints bioink, a suspension of bacteria in a solution of alginate that solidifies on a calcium-containing substrate. We 3D-printed Escherichia coli in different shapes and in discrete layers, after which the cells survived in the printing matrix for at least 1 week. When printed bacteria were induced to form curli fibers, the major proteinaceous extracellular component of E. coli biofilms, they remained adherent to the printing substrate and stably spatially patterned even after treatment with a matrix-dissolving agent, indicating that a biofilm-mimicking structure had formed. This work is the first demonstration of patterned, biofilm-inspired living materials that are produced by genetic control over curli formation in combination with spatial control by 3D printing. These materials could be used as living, functional materials in applications such as water filtration, metal ion sequestration, or civil engineering, and potentially as standardizable models for certain curli-containing biofilms.
Exploring the Technical Expression of Academic Knowledge: The Science-in-CTE Pilot Study

ERIC Educational Resources Information Center

Pearson, Donna; Young, R. Brent; Richardson, George B.

2013-01-01

The Science-in-CTE pilot study tested a curriculum integration model that enhanced the science that oc-curs in CTE curricula. The study replicated the National Research Center for Career and Technical Ed-ucation's (NRCCTE) Math-in-CTE experimental research design (Stone, Alfeld, & Pearson, 2008) with applied science in secondary agricultural…
Understanding Puberty (For Parents)

MedlinePlus

... his voice is changing and will become deeper. Dark, coarse, curly hair will also sprout just above ... in texture over the next year or two. Dark, coarse, curly hair will appear on her labia ( ...
The dual effect of curcumin nanoparticles encapsulated by 1-3/1-6 β-glucan from medicinal mushrooms Hericium erinaceus and Ganoderma lucidum

NASA Astrophysics Data System (ADS)

Huong Le, Mai; Doan Do, Hai; Tran Thi, Hong Ha; Dung, Le Vu; Nguyen, Hoai Nam; Nhu Tran Thi, Hang; Dinh Nguyen, Luyen; Hoang, Chi Kim; Le, Huu Cuong; Huong Le Thi, Thu; Trinh, Hoang Trung; Thu Ha, Phuong

2016-12-01

Curcumin is a polyphenol from turmeric Curcuma longa L that has been proved to possess numerous biological and pharmaceutical activities, including anti-cancer properties. However, curcumin has only limited clinical applications due to the aqueous insolubility characteristic that reduces its biological availability. On the other hand, using nanoparticles as drug delivery system has potential as it increases solubility of hydrophobic substances such as curcumin. Furthermore, nanoparticles can protect and control release of drug. Therefore, the objective of this project is to prepare nanoparticles by polymeric encapsulating curcumin by 1-3/1-6 β-glucan extracted from Vietnamese mushrooms to increase drug delivery efficiency and biological effect. Method of the preparation is nano-precipitation. The produced curcumin-β-glucan-nanoparticles (NanoGluCur) takes spherical shape with 60-70 nm in diameter. As expected, water solubility of curcumin increases about 180 times, from 0.6 μg ml-1 to 0.11 mg ml-1. Loading capacity of NanoGluCur is 18.16%. In vitro cytotoxicity and anti-tumor promoting effects of NanoGluCur were also investigated. Results revealed that NanoGluCur is able to inhibit the growth of two human cancer cell lines Hep-G2 and LU-1 with IC50 values of 6.82 and 15.53 mg ml-1, respectively, while free curcumin expresses the activity with IC50 values of 7.41 and 18.82 mg ml-1. At the concentration of 40 mg ml-1, NanoGluCur showed anti-tumor promoting effects in reducing tumor size by 59.93% and tumor density by 40.52%, while the percentages caused by pristine curcumin were 41.36% and 29.14%, respectively. These results demonstrated dual effect of 1-3/1-6 β-glucan encapsulated curcumin nanoparticles: higher water solubility and better in vitro anti-cancer effects compared to free curcumin and 1-3/1-6 β-glucan, expectedly. This observation can potentially open a new approach in research and manufacture of functional foods from medicinal mushrooms.
Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement

NASA Astrophysics Data System (ADS)

Budi Hartono, Sandy; Hadisoewignyo, Lannie; Yang, Yanan; Meka, Anand Kumar; Antaresti; Yu, Chengzhong

2016-12-01

In the present work, a simple method was used to develop composite curcumin-amine functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used to improve the bioavailability of curcumin in mice through oral administration. We investigated the effect of particle size on the release profile, solubility and oral bioavailability of curcumin in mice, including amine functionalized mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of MSN-A-Cur and MSM-A-Cur was considerably higher than that of ‘free curcumin’. These results indicate promising features of amine functionalized MSN as a carrier to deliver low solubility drugs with improved bioavailability via the oral route.
Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney.

PubMed

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh; Samini, Fariborz

2017-03-01

Restraint stress has been indicated to induce oxidative damage in tissues. Several investigations have reported that curcumin (CUR) may have a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CUR on restraint stress induced oxidative stress damage in the brain, liver and kidneys. For chronic restraint stress, rats were kept in the restrainers for 1h every day, for 21 consecutive days. The animals received systemic administrations of CUR daily for 21days. In order to evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), as well as antioxidant enzyme activities superoxide dismutase (SOD) glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were measured in the brain, liver and kidney of rats after the end of restraint stress. The restraint stress significantly increased MDA level, but decreased the level of GSH and activists of SOD, GPx, GR, and CAT the brain, liver and kidney of rats in comparison to the normal rats (P<0.001). Intraperitoneal administration of CUR significantly attenuated oxidative stress and lipid peroxidation, prevented apoptosis, and increased antioxidant defense mechanism activity in the tissues versus the control group (P<0.05). This study shows that CUR can prevent restraint stress-induced oxidative damage in the brain, liver and kidney of rats and propose that CUR may be useful agents against oxidative stress in the tissues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

PubMed

Zhao, Shuang; Ma, Litao; Cao, Chengwen; Yu, Qianqian; Chen, Lanmei; Liu, Jie

2017-01-01

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C 16 -SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C 16 -CC-CS-mPEG) was developed in a similar fashion to that used to yield C 16 -CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C 16 -SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C 16 -SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C 16 -SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C 16 -SS-CS-mPEG@Cur. Hence, C 16 -SS-CS-mPEG@Cur micelles can be useful in tumor therapy.
Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy

PubMed Central

Zhao, Shuang; Ma, Litao; Cao, Chengwen; Yu, Qianqian; Chen, Lanmei; Liu, Jie

2017-01-01

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C16-SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C16-CC-CS-mPEG) was developed in a similar fashion to that used to yield C16-CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C16-SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C16-SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C16-SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C16-SS-CS-mPEG@Cur. Hence, C16-SS-CS-mPEG@Cur micelles can be useful in tumor therapy. PMID:28408820
A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin

NASA Astrophysics Data System (ADS)

Mohammed, Fatima; Rashid-Doubell, Fiza; Cassidy, Seamas; Henari, Fryad

2017-08-01

Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of β-diketone group from curcumin. The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.
Transcriptomic analysis for genetic mechanisms of the factors related to biofilm formation in Escherichia coli O157:H7.

PubMed

Lee, Jin-Hyung; Kim, Yong-Guy; Cho, Moo Hwan; Wood, Thomas K; Lee, Jintae

2011-04-01

Two lineages of enterohemorrhagic Escherichia coli O157:H7 (EDL933, Stx1(+) and Stx2(+)) and 86-24 (Stx2(+)) were investigated to determine the genetic basis of biofilm formation on abiotic surfaces. Strain EDL933 formed a robust biofilm while strain 86-24 formed almost no biofilm on either polystyrene plates or polyethylene tubes. Whole-transcriptome profiles of EDL933 versus 86-24 revealed that in the strong biofilm-forming strain, genes involved in curli biosynthesis and cellulose production were significantly induced, whereas genes involved in indole signaling were most repressed. Additionally, 49 phage genes were highly induced and repressed between the two strains. Curli assays using Congo red plates and scanning electron microscopy corroborated the microarray data as the EDL933 strain produced a large amount of curli, while strain 86-24 formed much less curli. Moreover, EDL933 produced 19-fold more cellulose than 86-24, and indole production in EDL933 was two times lower than that of the strain 86-24. Therefore, it appears E. coli O157:H7 EDL933 produces more biofilm because of its increased curli and cellulose production and reduced indole production.
Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.

PubMed

Massaro, M; Amorati, R; Cavallaro, G; Guernelli, S; Lazzara, G; Milioto, S; Noto, R; Poma, P; Riela, S

2016-04-01

Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiff's base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage. Copyright © 2016 Elsevier B.V. All rights reserved.
Development of antibacterial paper coated with sodium hyaluronate stabilized curcumin-Ag nanohybrid and chitosan via polyelectrolyte complexation for medical applications

NASA Astrophysics Data System (ADS)

Rao Kummara, Madhusudana; Kumar, Anuj; Soo, Han Sung

2017-11-01

Sodium hyaluronate (HA) stabilized curcumin-Ag (Cur-Ag) hybrid nanoparticles were prepared in the water-ethanol mixture under constant mechanical stirring condition. The obtained HA stabilized Cur-Ag hybrid nanoparticles were characterized by fourier transform infrared spectroscopy, UV-visible spectroscopy, and x-ray diffraction to confirm the formation and structural interactions. The obtained Cur-Ag hybrid nanoparticles showed spherical shape with their size range 5-12 nm that was increased with the increasing a amount of silver ions as confirmed by transmission electron microscopic analysis. Further, a fibrous cellulose filter paper was impregnated with these hybrid nanoparticles and chitosan (CS) as biopolymer via polyelectrolyte complexation. The morphological analysis confirmed the uniform distribution of hybrid nanoparticle system onto the cellulose fibers of the fibrous filter paper. As per disc diffusion method, the Cur-Ag hybrid nanoparticles impregnated CS-coated filter paper exhibited excellent antibacterial properties against gram-negative Escherichia coli (E.coli) bacteria compared to HA stabilized Cur only. Moreover, as prepared hybrid nanoparticles impregnated biocomposite system is eco-friendly with efficient antibacterial property and have good potential to be used in medical applications.

Advances and challenges in hair restoration of curly Afrocentric hair.

PubMed

Rogers, Nicole E; Callender, Valerie D

2014-04-01

Although the biochemical composition of hair is similar among racial and ethnic groups, the hair structure between them varies, and individuals with curly hair pose specific challenges and special considerations when a surgical option for alopecia is considered. Hair restoration in this population should therefore be approached with knowledge on the clinical characteristics of curly hair, hair grooming techniques that may influence the management, unique indications for the procedure, surgical instrumentation used, and the complications that may arise. Copyright © 2014 Elsevier Inc. All rights reserved.
Influence of the amyloid dye Congo red on curli, cellulose, and the extracellular matrix in E. coli during growth and matrix purification.

PubMed

Reichhardt, Courtney; McCrate, Oscar A; Zhou, Xiaoxue; Lee, Jessica; Thongsomboon, Wiriya; Cegelski, Lynette

2016-11-01

Microbial biofilms are communities of cells characterized by a hallmark extracellular matrix (ECM) that confers functional attributes to the community, including enhanced cohesion, adherence to surfaces, and resistance to external stresses. Understanding the composition and properties of the biofilm ECM is crucial to understanding how it functions and protects cells. New methods to isolate and characterize ECM are emerging for different biofilm systems. Solid-state nuclear magnetic resonance was used to quantitatively track the isolation of the insoluble ECM from the uropathogenic Escherichia coli strain UTI89 and understand the role of Congo red in purification protocols. UTI89 assembles amyloid-integrated biofilms when grown on YESCA nutrient agar. The ECM contains curli amyloid fibers and a modified form of cellulose. Biofilms formed by UTI89 and other E. coli and Salmonella strains are often grown in the presence of Congo red to visually emphasize wrinkled agar morphologies and to score the production of ECM. Congo red is a hallmark amyloid-binding dye and binds to curli, yet also binds to cellulose. We found that growth in Congo red enabled more facile extraction of the ECM from UTI89 biofilms and facilitates isolation of cellulose from the curli mutant, UTI89ΔcsgA. Yet, Congo red has no influence on the isolation of curli from curli-producing cells that do not produce cellulose. Sodium dodecyl sulfate can remove Congo red from curli, but not from cellulose. Thus, Congo red binds strongly to cellulose and possibly weakens cellulose interactions with the cell surface, enabling more complete removal of the ECM. The use of Congo red as an extracellular matrix purification aid may be applied broadly to other organisms that assemble extracellular amyloid or cellulosic materials. Graphical abstract Solid-state NMR was used to quantitatively track the isolation of the insoluble amyloid-associated ECM from uropathogenic E. coli and understand the role of Congo red in purification protocols.
Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

PubMed

Chopra, Deepti; Ray, Lipika; Dwivedi, Ashish; Tiwari, Shashi Kant; Singh, Jyoti; Singh, Krishna P; Kushwaha, Hari Narayan; Jahan, Sadaf; Pandey, Ankita; Gupta, Shailendra K; Chaturvedi, Rajnish Kumar; Pant, Aditya Bhushan; Ray, Ratan Singh; Gupta, Kailash Chand

2016-04-01

Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products. Copyright © 2016 Elsevier Ltd. All rights reserved.
Moisture in Crawl Spaces

Treesearch

Anton TenWolde; Samuel V. Glass

2013-01-01

Crawl space foundations can be designed and built to avoid moisture problems. In this article we provide a brief overview of crawl spaces with emphasis on the physics of moisture. We review trends that have been observed in the research literature and summarize cur-rent recommendations for moisture control in crawl spaces.
Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition.

PubMed

Chen, Daquan; Lian, Shengnan; Sun, Jingfang; Liu, Zongliang; Zhao, Feng; Jiang, Yongtao; Gao, Mingming; Sun, Kaoxiang; Liu, Wanhui; Fu, Fenghua

2016-01-01

In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.
Photocatalytic performance of Ag doped SnO2 nanoparticles modified with curcumin

NASA Astrophysics Data System (ADS)

Vignesh, K.; Hariharan, R.; Rajarajan, M.; Suganthi, A.

2013-07-01

Visible light active Ag doped SnO2 nanoparticles modified with curcumin (Cur-Ag-SnO2) have been prepared by a combined precipitation and chemical impregnation route. The optical properties, phase structures and morphologies of the as-prepared nanoparticles were characterized using UV-visible diffuse reflectance spectra (UV-vis-DRS), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The surface area was measured by Brunauer. Emmett. Teller (B.E.T) analysis. Compared to bare SnO2, the surface modified photocatalysts (Ag-SnO2 and Cur-Ag-SnO2) showed a red shift in the visible region. The photocatalytic activity was monitored via the degradation of rose bengal (RB) dye and the results revealed that Cur-Ag-SnO2 shows better photocatalytic activity than that of Ag-SnO2 and SnO2. The superior photocatalytic activity of Cur-Ag-SnO2 could be attributed to the effective electron-hole separation by surface modification. The effect of photocatalyst concentration, initial dye concentration and electron scavenger on the photocatalytic activity was examined in detail. Furthermore, the antifungal activity of the photocatalysts and the reusability of Cur-Ag-SnO2 were tested.
Targeting superficial or nodular Basal cell carcinoma with topically formulated small molecule inhibitor of smoothened.

PubMed

Tang, Tracy; Tang, Jean Y; Li, Dongwei; Reich, Mike; Callahan, Christopher A; Fu, Ling; Yauch, Robert L; Wang, Frank; Kotkow, Karen; Chang, Kris S; Shpall, Elana; Wu, Angela; Rubin, Lee L; Marsters, James C; Epstein, Ervin H; Caro, Ivor; de Sauvage, Frederic J

2011-05-15

Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened. In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 (+/-) K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days. In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study. Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent. ©2011 AACR.
Selkirk Rex: Morphological and Genetic Characterization of a New Cat Breed

PubMed Central

2012-01-01

Rexoid, curly hair mutations have been selected to develop new domestic cat breeds. The Selkirk Rex is the most recently established curly-coated cat breed originating from a spontaneous mutation that was discovered in the United States in 1987. Unlike the earlier and well-established Cornish and Devon Rex breeds with curly-coat mutations, the Selkirk Rex mutation is suggested as autosomal dominant and has a different curl phenotype. This study provides a genetic analysis of the Selkirk Rex breed. An informal segregation analysis of genetically proven matings supported an autosomal, incomplete dominant expression of the curly trait in the Selkirk Rex. Homozygous curl cats can be distinguished from heterozygous cats by head and body type, as well as the presentation of the hair curl. Bayesian clustering of short tandem repeat (STR) genotypes from 31 cats that represent the future breeding stock supported the close relationship of the Selkirk Rex to the British Shorthair, Scottish Fold, Persian, and Exotic Shorthair, suggesting the Selkirk as part of the Persian breed family. The high heterozygosity of 0.630 and the low mean inbreeding coefficient of 0.057 suggest that Selkirk Rex has a diverse genetic foundation. A new locus for Selkirk autosomal dominant Rex, SADRE, is suggested for the curly trait. PMID:22837475
Neural tube defects induced by folate deficiency in mutant curly tail (Grhl3) embryos are associated with alteration in folate one-carbon metabolism but are unlikely to result from diminished methylation

PubMed Central

De Castro, Sandra CP; Leung, Kit-yi; Savery, Dawn; Burren, Katie; Rozen, Rima; Copp, Andrew J.; Greene, Nicholas D.E.

2013-01-01

Background Folate one-carbon metabolism has been implicated as a determinant of susceptibility to neural tube defects (NTDs), owing to the preventive effect of maternal folic acid supplementation and the higher risk associated with markers of diminished folate status. Methods Folate one-carbon metabolism was compared in curly tail (ct/ct) and genetically matched congenic (+ct/+ct) mouse strains using the deoxyuridine suppression test in embryonic fibroblast cells and by quantifying s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH) in embryos using liquid chromatography tandem mass spectrometry. A possible genetic interaction between curly tail and a null allele of 5,10-methylenetetrahydrofolate reductase (MTHFR) was investigated by generation of compound mutant embryos. Results There was no deficit in thymidylate biosynthesis in ct/ct cells but incorporation of exogenous thymidine was lower than in +ct/+ct cells. In +ct/+ct embryos the SAM/SAH ratio was diminished by dietary folate deficiency and normalised by folic acid or myor-inositol treatment, in association with prevention of NTDs. In contrast, folate deficiency caused a significant increase in SAM/SAH ratio in ct/ct embryos. Loss of MTHFR function in curly tail embryos significantly reduced the SAM/SAH ratio but did not cause cranial NTDs or alter the frequency of caudal NTDs. Conclusions Curly tail fibroblasts and embryos, in which Grhl3 expression is reduced, display alterations in one-carbon metabolism, particularly in the response to folate deficiency, compared with genetically-matched congenic controls in which Grhl3 is unaffected. However, unlike folate deficiency, diminished methylation potential appears to be insufficient to cause cranial NTDs in the curly tail strain, and neither does it increase the frequency of caudal NTDs. PMID:20589880
Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.

PubMed

Murakami, Akira; Furukawa, Ikuyo; Miyamoto, Shingo; Tanaka, Takuji; Ohigashi, Hajime

2013-01-01

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.
A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis.

PubMed

Salmazi, Rafael; Calixto, Giovana; Bernegossi, Jéssica; Ramos, Matheus Aparecido dos Santos; Bauab, Taís Maria; Chorilli, Marlus

2015-01-01

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.
Development and evaluation of a novel polymeric hydrogel of sucrose acrylate-co-polymethylacrylic acid for oral curcumin delivery.

PubMed

Huang, Sijin; Wang, Jialei; Shang, Qing

2017-02-01

A monomer of sucrose acrylate (AC-sucrose) was synthesized by conjugating starting compound sucrose with methyl acrylate (MA). The obtained AC-sucrose was characterized by mass spectrometry (MS) and Fourier transform infrared (FTIR) spectroscopy. AC-sucrose was selected as a monomer to fabricate a novel pH sensitive hydrogel via free radical polymerization. The inner morphology of the final hydrogel was observed with an S-4800 scanning electron microscope (SEM). The swelling and de-swelling behaviors of the hydrogel chips were also studied. Curcumin (CUR) was selected as a model drug and loaded into the final hydrogel. The release profiles of CUR were performed via dialysis method in pH 1.2, 6.8 and 7.4 buffers, respectively. Mass and FTIR spectra confirmed the synthesis of AC-sucrose. SEM photographs showed that poly(AC-sucrose-co-MAA) hydrogels had many 3D meshes. In pH 1.2 buffer, the hydrogel chips showed the biggest swelling ratio (SR) of 34.4 ± 1.9%. However, in pH 7.4 buffer, the SRs of the hydrogel chips reached to 368.7 ± 28.0%, which suggested that the hydrogel had an excellent pH sensibility. The releasing profiles showed that only 4.6 ± 0.4% of CUR was released in pH 1.2 buffer but 93.7 ± 4.7% of CUR was diffused into pH 7.4 buffer. These data suggested that the CUR-loaded poly (AC-sucrose-co-MAA) hydrogel could direct CUR to release in basic environments.
Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.
Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells.

PubMed

Patil, Sharvil; Choudhary, Bhavana; Rathore, Atul; Roy, Krishtey; Mahadik, Kakasaheb

2015-11-15

Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation. The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549. 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch. CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats. The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44. Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability. Copyright © 2015 Elsevier GmbH. All rights reserved.
Enhancement of curcumin wound healing ability by complexation with 2-hydroxypropyl-γ-cyclodextrin in sacran hydrogel film.

PubMed

Wathoni, Nasrul; Motoyama, Keiichi; Higashi, Taishi; Okajima, Maiko; Kaneko, Tatsuo; Arima, Hidetoshi

2017-05-01

Curcumin is one of promising agents to accelerate the wound-healing process. However, the efficacy of curcumin is limited due to its poor water solubility and stability. To enhance the properties of curcumin, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) can be used through complexation. Recently, we revealed that sacran has the potential to form a hydrogel film (HGF) as a wound dressing material. Therefore, in the present study, we investigated the wound healing ability of curcumin/HP-γ-CyD (Cur/HP-γ-CyD) complex in sacran-based HGF (Sac-HGF). We prepared the Cur/HP-γ-CyD complex in Sac-HGF without surface roughness. Additionally, the amorphous form in the Cur/HP-γ-CyD complex in Sac-HGF were observed. In contrast, the curcumin in Sac-HGF and curcumin/HP-γ-CyD physical mixture in Sac-HGF formed inhomogeneous films due to crystallization of curcumin. Furthermore, HP-γ-CyD played an important role to increase the elastic modulus of the Sac-HGF with high re-swelling ability. The Cur/HP-γ-CyD complex in Sac-HGF maintained antioxidant properties of curcumin. Curcumin was gradually released from the HP-γ-CyD complex in Sac-HGF. Notably, the Cur/HP-γ-CyD complex in Sac-HGF provided the highest wound healing ability in hairless mice. These results suggest that the Cur/HP-γ-CyD complex in Sac-HGF has the potential for use as a new transdermal therapeutic system to promote the wound-healing process. Copyright © 2017 Elsevier B.V. All rights reserved.
Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach.

PubMed

Tefas, Lucia Ruxandra; Sylvester, Bianca; Tomuta, Ioan; Sesarman, Alina; Licarete, Emilia; Banciu, Manuela; Porfire, Alina

2017-01-01

The aim of this work was to use the quality-by-design (QbD) approach in the development of long-circulating liposomes co-loaded with curcumin (CUR) and doxorubicin (DOX) and to evaluate the cytotoxic potential of these liposomes in vitro using C26 murine colon carcinoma cell line. Based on a risk assessment, six parameters, namely the phospholipid, CUR and DOX concentrations, the phospholipid:cholesterol molar ratio, the temperature during the evaporation and hydration steps and the pH of the phosphate buffer, were identified as potential risk factors for the quality of the final product. The influence of these variables on the critical quality attributes of the co-loaded liposomal CUR and DOX was investigated: particle size, zeta potential, drug loading and entrapment efficiency. For this, a 2 6-2 factorial design was employed to establish a proper regression model and to generate the contour plots for the responses. The obtained data served to establish the design space for which different combinations of variables yielded liposomes with characteristics within predefined specifications. The validation of the model was carried out by preparing two liposomal formulations corresponding to the robust set point from within the design space and one outside the design space and calculating the percentage bias between the predicted and actual experimental results. The in vitro antiproliferative test showed that at higher CUR concentrations, the liposomes co-encapsulating CUR and DOX had a greater cytotoxic effect than DOX-loaded liposomes. Overall, this study showed that QbD is a useful instrument for controlling and optimizing the manufacturing process of liposomes co-loaded with CUR and DOX and that this nanoparticulate system possesses a great potential for use in colon cancer therapy.
A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis

PubMed Central

Salmazi, Rafael; Calixto, Giovana; Bernegossi, Jéssica; Ramos, Matheus Aparecido dos Santos; Bauab, Taís Maria; Chorilli, Marlus

2015-01-01

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis. PMID:26257519
PEG-coumarin nanoaggregates as π-π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery.

PubMed

Behl, Gautam; Kumar, Parveen; Sikka, Manisha; Fitzhenry, Laurence; Chhikara, Aruna

2018-03-01

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π-π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π-π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π-π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π-π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (D av ) was in the range of 120-160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC 50 ~11 and ~15 μM as compared to free CUR, IC 50 ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.
Cur l 3, a major allergen of Curvularia lunata-derived short synthetic peptides, shows promise for successful immunotherapy.

PubMed

Sharma, Vidhu; Singh, Bhanu Pratap; Arora, Naveen

2011-12-01

Allergens with reduced IgE binding and intact T cell reactivity are required for safety and efficacy of immunotherapy (IT). Curvularia lunata is an important fungus for respiratory allergic disorders having cross-reactive and specific allergens. Previously, we have identified major allergens-namely, Cur l 1 (31 kD, serine protease), Cur l 2 (48 kD, enolase), and Cur l 3 (12 kD, cytochrome c)-from this fungus. Furthermore, Cur l 3 epitope-peptide, P6, showed immunogenicity and higher IgE binding, where cysteine and histidine were observed to be vital for IgE binding. Thus, this peptide and three derivatives with reduced IgE binding were selected for analysis in mice. In the present study, the effect of IT was assessed with Cur l 3, P6, its derivatives (P6.1-6.3), and P10 in a mouse model of allergy. IT with P6.2 and P10 reduced IgE and IgG1 levels significantly (P < 0.05), with increase in IgG2a levels as compared to other antigens. There was a significant reduction of IL-4 level associated with increased IFN-γ after IT. Airway inflammation was reduced significantly in terms of eosinophil counts in lung tissue and bronchoalveolar lavage fluid. IT with P6 and P6.2 induced significantly higher IL-10 secretion than baseline after 40 days of treatment. Generally, the effect of IT was more pronounced after 40 days than after 10 days of treatment. In summary, the modified peptide, P6.2, with reduced IgE binding, but intact immunogenicity, showed promise for successful IT.
Transfer of Salmonella enterica serovar Typhimurium from contaminated irrigation water to parsley is dependent on curli and cellulose, the biofilm matrix components.

PubMed

Lapidot, Anat; Yaron, Sima

2009-03-01

Enteric pathogens can contaminate fresh produce, and this contaminated produce can be a significant potential source of human illness. The objective of this study was to determine a possible mode of transfer of Salmonella Typhimurium from contaminated irrigation water to mature parsley plants and to investigate the role of bacterial cellulose and curli. Parsley plants were drip irrigated with water containing green fluorescent protein-labeled Salmonella Typhimurium. Stems and leaves were harvested 1 day after the third irrigation and examined for the presence of Salmonella Typhimurium. Three weeks after harvesting, the presence of Salmonella was again confirmed in the regrown plants. During this period, bacterial numbers on leaves declined from 4.1 (+/- 0.3) to 2.3 (+/- 0.1) log CFU g(-1) (P < 0.05). Numbers in the soil were constant (5 log CFU g(-1)). Results demonstrated the ability of Salmonella Typhimurium to transfer from irrigation water to the edible parts of the plants. Confocal laser scanning microscopic images revealed that Salmonella Typhimurium formed aggregates at a depth of 8 to 32 microm beneath the leaf surface. Penetration might be achieved through the roots or the phyllosphere. The importance of the bacterial cellulose and curli was determined by comparing the wild-type strain with its mutants, which lack the ability to synthesize cellulose and curli. Counts of the double mutant were 2-log higher in the soil but 1-log lower in the leaves (P < 0.05). Deletion of the agfBA gene (for curli) was more effective than deletion of bcsA (for cellulose). Thus, curli and cellulose play a role in the transfer or survival of Salmonella Typhimurium in the plant, as they do for plant pathogens.

Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI).

PubMed

Cheng, Kwok Kin; Chan, Pui Shan; Fan, Shujuan; Kwan, Siu Ming; Yeung, King Lun; Wáng, Yì-Xiáng J; Chow, Albert Hee Lum; Wu, Ed X; Baum, Larry

2015-03-01

Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of amyloid imaging. The current method relies on positron emission tomography (PET), which is expensive and exposes people to radiation, undesirable features for a population screening method. Magnetic resonance imaging (MRI) is cheaper and is not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone by antisolvent precipitation in a multi-inlet vortex mixer produces stable and biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter <100 nm. These nanoparticles were visualized by transmission electron microscopy and atomic force microscopy, and their structure and chemistry were further characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and Fourier transform infrared spectroscopy. Cur-MNPs exhibited no cytotoxicity in either Madin-Darby canine kidney (MDCK) or differentiated human neuroblastoma cells (SH-SY5Y). The Papp of Cur-MNPs was 1.03 × 10(-6) cm/s in an in vitro blood-brain barrier (BBB) model. Amyloid plaques could be visualized in ex vivo T2*-weighted magnetic resonance imaging (MRI) of Tg2576 mouse brains after injection of Cur-MNPs, and no plaques could be found in non-transgenic mice. Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non-invasive diagnosis of AD using MRI. Copyright © 2014 Elsevier Ltd. All rights reserved.
Antiproliferative effects of fresh and thermal processed green and red cultivars of curly kale (Brassica oleracea L. convar. acephala var. sabellica).

PubMed

Olsen, Helle; Grimmer, Stine; Aaby, Kjersti; Saha, Shikha; Borge, Grethe Iren A

2012-08-01

Brassica vegetables contain a diverse range of phytochemicals with biological properties such as antioxidant and anticancer activity. However, knowledge about how biological activities are affected by processing is lacking. A green cultivar and a red cultivar of curly kale were evaluated for water/methanol-soluble phytochemicals before and after processing involving blanching, freeze storage, and boil-in-bag heat treatment. In both kale cultivars, processing resulted in a significant decrease of total phenolics, antioxidant capacity, and content and distribution of flavonols, anthocyanins, hydroxycinnamic acids, glucosinolates, and vitamin C. Interestingly, the red curly kale cultivar had a higher capacity to withstand thermal loss of phytochemicals. The extracts of both green and red curly kale inhibited the cell proliferation of three human colon cancer cell lines (Caco-2, HT-29, and HCT 116). However, extracts from fresh plant material had a significantly stronger antiproliferative effect than extracts from processed plant material.
Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin.

PubMed

El-Beshbishy, Hesham A; Mohamadin, Ahmed M; Nagy, Ayman A; Abdel-Naim, Ashraf B

2010-03-01

Liver injury was induced in female rats using tamoxifen (TAM). Grape seeds (Vitis vinifera) extract (GSE), black seed (Nigella sativa) extract (NSE), curcumin (CUR) or silymarin (SYL) were orally administered to TAM-intoxicated rats. Liver histopathology of TAM-intoxicated:rats showed pathological changes. TAM-intoxication elicited declines in liver antioxidant enzymes levels (glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase), reduced glutathione (GSH) and GSH/GSSG ratio plus the hepatic elevations in lipid peroxides, oxidized glutathione (GSSG), tumor necrosis factor-alpha (TNF-alpha) and serum liver enzymes; alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase levels. Oral intake of NSE, GSE, CUR or SYL to TAM-intoxicated rats, attenuated histopathological changes and corrected all parameters mentioned above. Improvements were prominent in case of NSE (similarly SYL) > CUR > GSE. Data indicated that NSE, GSE or CUR act as free radicals scavengers and protect TAM-induced liver injury in rats.
The effect of curcumin in the ectonucleotidases and acetylcholinesterase activities in synaptosomes from the cerebral cortex of cigarette smoke-exposed rats.

PubMed

Jaques, Jeandre Augusto Dos Santos; Rezer, João Felipe Peres; Gonçalves, Jamile Fabbrin; Spanevello, Rosélia Maria; Gutierres, Jessié Martins; Pimentel, Victor Câmera; Thomé, Gustavo Roberto; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

2011-12-01

With the evidence that curcumin may be a potent neuroprotective agent and that cigarette smoke is associated with a decline in the cognitive performance as our bases, we investigated the activities of Ecto-Nucleoside Triphosphate Diphosphohydrolase (NTPDase), 5'-nucleotidase and acetylcholinesterase (AChE) in cerebral cortex synaptosomes from cigarette smoke-exposed rats treated with curcumin (Cur). The experimental procedures entailed two sets of experiments. In the first set, the groups were vehicle, Cur 12·5, 25 and 50 mg·kg(-1) ; those in the second set were vehicle, smoke, smoke and Cur 12·5, 25 and 50 mg·kg(-1) . Curcumin prevented the increased NTPDase, 5'-nucleotidase and AChE activities caused by smoke exposure. We suggest that treatment with Cur was protective because the decrease of ATP and acetylcholine (ACh) concentrations is responsible for cognitive impairment, and both ATP and ACh have key roles in neurotransmission. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

PubMed

Wojcik, Marzena; Krawczyk, Michal; Wojcik, Pawel; Cypryk, Katarzyna; Wozniak, Lucyna Alicja

2018-01-01

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric Curcuma longa , has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.
Control of the Biofilms Formed by Curli- and Cellulose-Expressing Shiga Toxin-Producing Escherichia coli Using Treatments with Organic Acids and Commercial Sanitizers.

PubMed

Park, Yoen Ju; Chen, Jinru

2015-05-01

Biofilms are a mixture of bacteria and extracellular products secreted by bacterial cells and are of great concern to the food industry because they offer physical, mechanical, and biological protection to bacterial cells. This study was conducted to quantify biofilms formed by different Shiga toxin-producing Escherichia coli (STEC) strains on polystyrene and stainless steel surfaces and to determine the effectiveness of sanitizing treatments in control of these biofilms. STEC producing various amounts of cellulose (n = 6) or curli (n = 6) were allowed to develop biofilms on polystyrene and stainless steel surfaces at 28°C for 7 days. The biofilms were treated with 2% acetic or lactic acid and manufacturer-recommended concentrations of acidic or alkaline sanitizers, and residual biofilms were quantified. Treatments with the acidic and alkaline sanitizers were more effective than those with the organic acids for removing the biofilms. Compared with their counterparts, cells expressing a greater amount of cellulose or curli formed more biofilm mass and had greater residual mass after sanitizing treatments on polystyrene than on stainless steel. Research suggests that the organic acids and sanitizers used in the present study differed in their ability to control biofilms. Bacterial surface components and cell contact surfaces can influence both biofilm formation and the efficacy of sanitizing treatments. These results provide additional information on control of biofilms formed by STEC.
Integrated miRNA-mRNA analysis reveals regulatory pathways underlying the curly fleece trait in Chinese tan sheep.

PubMed

Liu, Yufang; Zhang, Jibin; Xu, Qiao; Kang, Xiaolong; Wang, Kejun; Wu, Keliang; Fang, Meiying

2018-05-11

Tan sheep is an indigenous Chinese breed well known for its beautiful curly fleece. One prominent breed characteristic of this sheep breed is that the degree of curliness differs markedly between lambs and adults, but the molecular mechanisms regulating the shift are still not well understood. In this study, we identified 49 differentially expressed (DE) microRNAs (miRNAs) between Tan sheep at the two stages through miRNA-seq, and combined the data with that in our earlier Suppression Subtractive Hybridization cDNA (SSH) library study to elucidate the mechanisms underlying curly fleece formation. Thirty-six potential miRNA-mRNA target pairs were identified using computational methods, including 25 DE miRNAs and 10 DE genes involved in the MAPK signaling pathway, steroid biosynthesis and metabolic pathways. With the differential expressions between lambs and adults confirmed by qRT-PCR, some miRNAs were already annotated in the genome, but some were novel miRNAs. Inhibition of KRT83 expression by miR-432 was confirmed by both gene knockdown with siRNA and overexpression, which was consistent with the miRNAs and targets prediction results. Our study represents the comprehensive analysis of mRNA and miRNA in Tan sheep and offers detailed insight into the development of curly fleece as well as the potential mechanisms controlling curly hair formation in humans.
The Role of Thin Aggregative Fimbriae on Pathogenic Bacterial Transport Through Porous Media

NASA Astrophysics Data System (ADS)

Salvucci, A. E.; Fuka, D. R.; Marjerison, R. D.; Hay, A. G.; Zhang, W.; Caballero, L. A.; Zevi, Y.; Richards, B. K.; Steenhuis, T. S.

2008-05-01

Pathogenic bacteria, such as Escherichia coli and Salmonella sp., are responsible for many deaths worldwide every year. Their survival in the natural environment is enhanced by the production of biofilms, which provide a resistance to environmental stresses. However, it remains unclear how these biofilms affect the bacterias' ability to move through the soil matrix and potentially contaminate groundwater or water from drainage systems. In this presentation, we discuss the role of thin aggregative fimbriae (curli), a key biofilm component, on transport through porous media. An experiment was performed consisting of 96 sand columns created using a deep-well microtiter plate. We used well-characterized strains of E. coli, one with the ability to form curli and one without. Pulsing the E. coli strains through the sand column, mimicking natural leaching processes, showed less transport, by greater retention, in the strains that produce curli versus those strains that do not. In addition, when cultured in conditions unfavorable to curli production, transport between strains did not differ significantly. These preliminary results indicate that curli, and to a larger extent biofilms, could be an important component influencing the transport of bacterial strains through the soil matrix. This determination of pathogens' ability to move through the environment, as related to how well they form biofilms, will facilitate a better understanding of the fate of pathogenic bacteria in the environment.
Automated diagnoses of attention deficit hyperactive disorder using magnetic resonance imaging.

PubMed

Eloyan, Ani; Muschelli, John; Nebel, Mary Beth; Liu, Han; Han, Fang; Zhao, Tuo; Barber, Anita D; Joel, Suresh; Pekar, James J; Mostofsky, Stewart H; Caffo, Brian

2012-01-01

Successful automated diagnoses of attention deficit hyperactive disorder (ADHD) using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scientific and diagnostic impacts of the research. We created a prediction model using the landmark ADHD 200 data set focusing on resting state functional connectivity (rs-fc) and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other covariates. The novel contributions of this manuscript include a thorough exploration of prediction and image feature extraction methodology on this form of data, including the use of singular value decompositions (SVDs), CUR decompositions, random forest, gradient boosting, bagging, voxel-based morphometry, and support vector machines as well as important insights into the value, and potentially lack thereof, of imaging biomarkers of disease. The key results include the CUR-based decomposition of the rs-fc-fMRI along with gradient boosting and the prediction algorithm based on a motor network parcellation and random forest algorithm. We conjecture that the CUR decomposition is largely diagnosing common population directions of head motion. Of note, a byproduct of this research is a potential automated method for detecting subtle in-scanner motion. The final prediction algorithm, a weighted combination of several algorithms, had an external test set specificity of 94% with sensitivity of 21%. The most promising imaging biomarker was a correlation graph from a motor network parcellation. In summary, we have undertaken a large-scale statistical exploratory prediction exercise on the unique ADHD 200 data set. The exercise produced several potential leads for future scientific exploration of the neurological basis of ADHD.
Automated diagnoses of attention deficit hyperactive disorder using magnetic resonance imaging

PubMed Central

Eloyan, Ani; Muschelli, John; Nebel, Mary Beth; Liu, Han; Han, Fang; Zhao, Tuo; Barber, Anita D.; Joel, Suresh; Pekar, James J.; Mostofsky, Stewart H.; Caffo, Brian

2012-01-01

Successful automated diagnoses of attention deficit hyperactive disorder (ADHD) using imaging and functional biomarkers would have fundamental consequences on the public health impact of the disease. In this work, we show results on the predictability of ADHD using imaging biomarkers and discuss the scientific and diagnostic impacts of the research. We created a prediction model using the landmark ADHD 200 data set focusing on resting state functional connectivity (rs-fc) and structural brain imaging. We predicted ADHD status and subtype, obtained by behavioral examination, using imaging data, intelligence quotients and other covariates. The novel contributions of this manuscript include a thorough exploration of prediction and image feature extraction methodology on this form of data, including the use of singular value decompositions (SVDs), CUR decompositions, random forest, gradient boosting, bagging, voxel-based morphometry, and support vector machines as well as important insights into the value, and potentially lack thereof, of imaging biomarkers of disease. The key results include the CUR-based decomposition of the rs-fc-fMRI along with gradient boosting and the prediction algorithm based on a motor network parcellation and random forest algorithm. We conjecture that the CUR decomposition is largely diagnosing common population directions of head motion. Of note, a byproduct of this research is a potential automated method for detecting subtle in-scanner motion. The final prediction algorithm, a weighted combination of several algorithms, had an external test set specificity of 94% with sensitivity of 21%. The most promising imaging biomarker was a correlation graph from a motor network parcellation. In summary, we have undertaken a large-scale statistical exploratory prediction exercise on the unique ADHD 200 data set. The exercise produced several potential leads for future scientific exploration of the neurological basis of ADHD. PMID:22969709
Curcumin as an amyloid-indicator dye in E. coli.

PubMed

McCrate, Oscar A; Zhou, Xiaoxue; Cegelski, Lynette

2013-05-14

We have demonstrated that curcumin is an amyloid-specific dye in E. coli. Curcumin binds to curliated whole cells and to isolated curli amyloid fibers. Similar to Congo red, curcumin exhibits a red-shift in absorbance and a significant increase in fluorescence upon binding to isolated curli.
Curcumin as an Amyloid-indicator Dye in E. coli †

PubMed Central

McCrate, Oscar A.; Zhou, Xiaoxue; Cegelski, Lynette

2013-01-01

We have demonstrated that curcumin is an amyloid-specific dye in E. coli. Curcumin binds to curliated whole cells and to isolated curli amyloid fibers. Similar to Congo red, curcumin exhibits a red-shift in absorbance and a significant increase in fluorescence upon binding to isolated curli. PMID:23287899
Beet curly top resistance in USDA-ARS Ft. Collins Germplasm, 2012

USDA-ARS?s Scientific Manuscript database

Seventeen sugar beet (Beta vulgaris L.) lines from the USDA-ARS Ft. Collins sugar beet program were screened for resistance to Beet severe curly top virus (BSCTV) and other closely related Curtovirus species in 2012. Commercial sugar beet cultivars Monohikari and HM PM90 were included as susceptibl...
Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1beta

USDA-ARS?s Scientific Manuscript database

Background: Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur's bioavailab...
'NuMex Las Cruces' Cayenne pepper

USDA-ARS?s Scientific Manuscript database

‘NuMex Las Cruces’ is a high-yielding, high-heat, cayenne pepper with a maturity similar to that of ‘Large Red Thick’, an early maturing cayenne cultivar. In addition, it possesses resistance to curly top virus, having resistance to at least three Curtovirus species: Beet curly top virus (BCTV; for...
Role of curli expression by Escherichia coli O157:H7 on the cell’s ability to attach to spinach

USDA-ARS?s Scientific Manuscript database

Introduction: Shiga-toxigenic Escherichia coli O157:H7 (STEC) outbreaks have been linked to consumption of fresh produce. Mechanisms of bacterial interaction with plant surfaces should be investigated to develop mitigation strategies. Cellular appendages, such as curli fibers have been suggested t...
Media composition and incubation temperature affect Congo red dye affinity of Shiga toxin-producing Escherichia coli

USDA-ARS?s Scientific Manuscript database

Background: Escherichia coli biofilm formation is dependent on curli fimbriae and cellulose, and the expression of both varies among Shiga toxin-producing E. coli (STEC). Curli and cellulose expression are often identified by their affinity for Congo red dye (CR) but media composition and incubation...
Neonicotinoid Seed Treatments and Foliar Sprays on Sugarbeet for Control of Severe Curly Top

USDA-ARS?s Scientific Manuscript database

Sugarbeet production in semiarid regions is hindered by yield loss caused with Beet severe curly top virus and other closely related species vectored by the beet leafhopper. In 2010, a study was established to investigate the level of control from seed treatments and supplemental foliar insecticide...
Characterization of phenolics, glucosinolates and antioxidant activity of beverages based on apple juice with addition of frozen and freeze-dried curly kale leaves (Brassica oleracea L. var. acephala L.).

PubMed

Biegańska-Marecik, Róża; Radziejewska-Kubzdela, Elżbieta; Marecik, Roman

2017-09-01

The aim of this study was to determine the polyphenols, glucosinolates and ascorbic acid content as well as antioxidant activity of beverages on the base of apple juice with addition of frozen and freeze-dried curly kale leaves. Upon enrichment with frozen (13%) and freeze-dried curly kale (3%), the naturally cloudy apple juice was characterized by an increase in phenolic compounds by 2.7 and 3.3-times, accordingly. The antioxidant activity of beverages with the addition of curly kale ranged from 6.6 to 9.4μmol Trolox/mL. The obtained beverages were characterized glucosinolates content at 117.6-167.6mg/L and ascorbic acid content at 4,1-31,9mg/L. The results of sensory evaluation of colour, taste and consistency of apple juice and beverages with the addition of kale did not differ significantly prior to pasteurization (P≤0.05), whereas after the pasteurization the evaluated factors decreased significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.
In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies.

PubMed

Anitha, A; Sreeranganathan, Maya; Chennazhi, Krishna Prasad; Lakshmanan, Vinoth-Kumar; Jayakumar, R

2014-09-01

Colon cancer is the third most leading causes of death due to cancer worldwide and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon cancer chemo treatment could be improved by nanoencapsulation and combinatorial approach. In the present study curcumin (CUR), a known anticancer phytochemical, was used in combination with 5-FU and the work focuses on the development of a combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs were found to be blood compatible. The in vitro drug release profile in pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days. The combined exposure of the nanoformulations in colon cancer cells (HT 29) proved the enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in mouse model revealed the improved plasma concentrations of 5-FU and CUR which prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and improved plasma concentrations under in vivo conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of PrestoBlue® and plating method to evaluate antimicrobial activity of ascorbic acid, boric acid and curcumin in an in vitro gastrointestinal model.

PubMed

Hernandez-Patlan, D; Solis-Cruz, B; Méndez-Albores, A; Latorre, J D; Hernandez-Velasco, X; Tellez, G; López-Arellano, R

2018-02-01

To compare the conventional plating method vs a fluorometric method using PrestoBlue ® as a dye by determining the antimicrobial activity of two organic acids and curcumin (CUR) against Salmonella Enteritidis in an avian in vitro digestion model that simulates the crop, proventriculus and intestine. A concentration of 10 8 CFU per ml of S. Enteritidis was exposed to groups with different rates of ascorbic acid (AA), boric acid (BA) and CUR. Significant differences were observed when the means of the treatments were compared with the controls in the compartments that simulate the crop and intestine (P < 0·05). Ascorbic acid alone and high rates of AA in the mixtures were the most efficient treatments in the crop compartment. However, in the intestinal compartment BA alone and at different rates in the mixture BA-CUR (1 : 1) were the best treatments to decrease the concentration of S. Enteritidis. The results of this study suggest that there could be an antagonistic bactericidal effect between AA and CUR and AA and BA as well as a synergistic bactericidal effect between BA and CUR. These findings may contribute to the development of a formulation with microencapsulated compounds to liberate them in different compartments to combat S. Enteritidis infections in broiler chickens. © 2017 The Society for Applied Microbiology.
PEGylated Lipid bilayer coated mesoporous silica nanoparticles for co-delivery of paclitaxel and curcumin: Design, characterization and its cytotoxic effect.

PubMed

Lin, Jiahao; Cai, Qiang; Tang, Yinian; Xu, Yanjun; Wang, Qian; Li, Tingting; Xu, Huihao; Wang, Shuaiyu; Fan, Kai; Liu, Zhongjie; Jin, Yipeng; Lin, Degui

2018-01-30

Highly ordered mesoporous silica nanoparticles (MSNs) with pore diameter of 2.754nm and particle size of 115±15nm were prepared with etching method. Homogeneous PEGylated lipid bilayer with 10-15nm thickness was coated around the surface of MSNs using film hydration method. Systematic optimization and characterization of co-encapsulation process of paclitaxel (Tax) and curcumin (Cur) into PEGylated lipid bilayer coated mesoporous silica nanoparticles (PLMSNs) were performed carrying out single factor test, associated with Box-Behnken Design. The concentration of encapsulated drugs was measured by reversed phase high performance liquid chromatography (RP-HPLC) method. Optimal factor settings were as follows: 50mg MSNs, ratio of MSNs to lipid (w/w)=1:1.11, and ratio of lipid to CHO (w/w)=3.93:1. The average experimental EE Tax , EE Cur and stability score value were (77.48±2.73) %, (30.70±3.56) % and 4 point respectively based on the conditions mentioned above. Morphology determination of Tax-Cur-PLMSNs revealed that the composite nanoparticles were spherical particals with uniform dispersion. In vitro release experiment indicated that PLMSNs improved dissolution of Tax compared to Tax powder suspension and exhibited sustained release property. Tax-Cur-PLMSNs manifested definite and persistently promoted cytotoxic effect against canine breast cancer cells. This prolonged and enhanced activity of Tax-Cur-PLMSNs might contribute to its sustained release effect. Copyright © 2017. Published by Elsevier B.V.
Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo.

PubMed

Gou, MaLing; Men, Ke; Shi, HuaShan; Xiang, MingLi; Zhang, Juan; Song, Jia; Long, JianLin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, ZhiYong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.
Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release of Curcumin.

PubMed

Alves, Thais F R; das Neves Lopes, Franciely C C; Rebelo, Marcia A; Souza, Juliana F; da Silva Pontes, Katiusca; Santos, Carolina; Severino, Patricia; Junior, Jose M O; Komatsu, Daniel; Chaud, Marco V

2018-01-01

The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801). SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR. The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Sulindac, 3,3'-diindolylmethane and curcumin reduce carcinogenesis in the Pirc rat, an Apc-driven model of colon carcinogenesis.

PubMed

Femia, Angelo Pietro; Soares, Paulo Victoria; Luceri, Cristina; Lodovici, Maura; Giannini, Augusto; Caderni, Giovanna

2015-09-03

Recently, we showed that Sulindac (SU; 320 ppm) reduces precancerous lesions in the colon of Pirc rats, mutated in the Apc gene. Surprisingly, previous data in Apc-mutated mice showed that SU, with reported efficacy in Familial Adenomatous Polyposis (FAP), increases colon carcinogenesis. Therefore, we assessed the effect of SU 320 ppm in a long-term carcinogenesis experiment in Pirc rats. Moreover, since side effects of SU hamper its chronic use and a combination of drugs could be more effective and less toxic than single agents, we also studied whether two natural compounds, 3,3'-diindolylmethane (DIM; 250 ppm) and curcumin (CUR; 2000 ppm), with or without lower doses of SU could affect carcinogenesis Pirc rats were fed an AIN76 diet containing SU, DIM and CUR and sacrificed at 8 months of age to measure intestinal tumours. Apoptosis and proliferation in the normal colon mucosa, as well as gene expression profile were studied Colon tumours were significantly reduced by SU 320 ppm (62 % reduction over Controls), by DIM and CUR without or with SU 80 and 160 ppm (50, 53 and 58 % reduction, respectively) but not by SU 80 ppm alone. Total tumours (colon and small intestine) were reduced by SU (80 and 320 ppm) and by DIM and CUR. Apoptosis in the normal mucosa was significantly increased by SU 320 ppm, and slightly increased by DIM and CUR with or without SU. A slight reduction in Survivin-Birc5 expression was observed with all the treatments compared to Controls. Proliferative activity was not varied The results on SU reinforce the validity of Pirc rats to identify chemopreventive products. Moreover, the efficacy of the DIM and CUR combination to lower colon tumours, suggests an alternative strategy to be exploited in patients at risk.
Transcriptome Profile at Different Physiological Stages Reveals Potential Mode for Curly Fleece in Chinese Tan Sheep

PubMed Central

Liu, Yufang; Xu, Qinqin; Zhang, Ming; Fang, Meiying

2013-01-01

Tan sheep (Ovis aries), a Chinese indigenous breed, has special curly fleece after birth, especially at one month old. However, this unique phenotype disappears gradually with age and the underlying reasons of trait evolvement are still unknown. In this study, skin transcriptome data was used to study this issue. In total 51,215 transcripts including described transcripts and transfrags were identified. Pathway analysis of the top 100 most highly expressed transcripts, which included TCHH and keratin gene family members, such as KRT25, KRT5, KRT71, KRT14 and others, showed pathways known to be relevant to hair/fleece development and function. Six hundred differentially expressed (DE) transcripts were detected at two different physiological ages (one-month-old with curly fleece and 48-month-old without curly fleece) and were categorized into three major functional groups: cellular component, molecular function, and biological process. The top six functional categories included cell, cell part, cellular process, binding, intracellular, metabolic process. The detected differentially expressed genes were particularly involved in signal, signal peptide, disulfide bond, glycoprotein and secreted terms, respectively. Further splicing isoform analysis showed that the metallothionein 3 isoform was up-regulated in Tan lamb skin, indicating that it may be related to the conformation of curly fleece in Chinese Tan lamb. The hair-related important differentially expressed genes (SPINK4, FGF21, ESRα, EphA3, NTNG1 and GPR110) were confirmed by qPCR analysis. We deduced that the differences existed in expressed transcripts, splice isoforms and GO categories between the two different physiological stages, which might constitute the major reasons for explaining the trait evolvement of curly fleece in Chinese Tan sheep. This study provides some clues for elucidating the molecular mechanism of fleece change with age in Chinese Tan sheep, as well as supplying some potential values for understanding human hair disorder and texture changes. PMID:23990983
Sequence‑dependent effect of sorafenib in combination with natural phenolic compounds on hepatic cancer cells and the possible mechanism of action.

PubMed

Bahman, Abdulmajeed A; Abaza, Mohamed Salah I; Khoushiash, Sarah I; Al-Attiyah, Rajaa J

2018-06-08

Sorafenib (Nexavar, BAY43‑9006 or Sora) is the first molecular targeted agent that has exhibited significant therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond well to Sora and novel therapeutic strategies to optimize the efficacy of Sora are urgently required. Plant‑based drugs have received increasing attention owing to their excellent chemotherapeutic and chemopreventive activities; they are also well tolerated, non‑toxic, easily available and inexpensive. It is well known that certain biologically active natural products act synergistically with synthetic drugs used in clinical applications. The present study aimed to investigate whether a combination therapy with natural phenolic compounds (NPCs), including curcumin (Cur), quercetin (Que), kaempherol (Kmf) and resveratrol (Rsv), would allow a dose reduction of Sora without concomitant loss of its effectiveness. Furthermore, the possible molecular mechanisms of this synergy were assessed. The hepatic cancer cell lines Hep3b and HepG2 were treated with Sora alone or in combination with NPCs in concomitant, sequential, and inverted sequential regimens. Cell proliferation, cell cycle, apoptosis and expression of proteins associated with the cell cycle and apoptosis were investigated. NPCs markedly potentiated the therapeutic efficacy of Sora in a sequence‑, type‑, NPC dose‑ and cell line‑dependent manner. Concomitant treatment with Sora and Cur [sensitization ratio (SR)=28], Kmf (SR=18) or Que (SR=8) was associated with the highest SRs in Hep3b cells. Rsv markedly potentiated the effect of Sora (SR=17) on Hep3b cells when administered in a reverse sequential manner. By contrast, Rsv and Que did not improve the efficacy of Sora against HepG2 cells, while concomitant treatment with Cur (SR=10) or Kmf (SR=4.01) potentiated the cytotoxicity of Sora. Concomitant treatment with Sora and Cur or Kmf caused S‑phase and G2/M phase arrest of liver cancer cells and markedly induced apoptosis compared with mono‑treatment with Sora, Cur or Kmf. Concomitant treatment with Sora and Cur reduced the protein levels of cyclins A, B2 and D1, phosphorylated retinoblastoma and B‑cell lymphoma (Bcl) extra‑large protein. By contrast, Sora and Cur co‑treatment increased the protein levels of Bcl‑2‑associated X protein, cleaved caspase‑3 and cleaved caspase‑9 in a dose‑dependent manner. In conclusion, concomitant treatment with Sora and Cur or Kmf appears to be a potent and promising therapeutic approach that may control hepatic cancer by triggering cell cycle arrest and apoptosis. Additional studies are required to examine the potential of combined treatment with Sora and NPCs in human hepatic cancer and other solid tumor types in vivo.
Growth media and temperature effects on biofilm formation by serotype O157:H7 and non-O157 Shiga toxin-producing Escherichia coli

USDA-ARS?s Scientific Manuscript database

Biofilm formation in most Escherichia coli strains is dependent on curli fimbriae and cellulose, and the expression of both varies widely among pathogenic strains. Curli and cellulose expression are often identified by their affinity for Congo red dye (CR). However, media composition and incubation ...
A novel nanofiber Cur-loaded polylactic acid constructed by electrospinning

NASA Astrophysics Data System (ADS)

Thu Trang Mai, Thi; Thu Thuy Nguyen, Thi; Duong Le, Quang; Ngoan Nguyen, Thi; Cham Ba, Thi; Binh Nguyen, Hai; Bich Hoa Phan, Thi; Tran, Dai Lam; Phuc Nguyen, Xuan; Park, Jun Seo

2012-06-01

Curcumin (Cur), extracted from the Curcuma longa L. plant, is well known for its anti-tumor, anti-oxidant, anti-inflammatory and anti-bacterial properties. Nanofiber mats of polylactic acid (PLA) loading Cur (5 wt%) were fabricated by electrospinning (e-spinning). Morphology and structure of the fibers were characterized by field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared (FTIR) spectroscopy, respectively. The diameters of the obtained fibers varied from 200 to 300 nm. The release capacity of curcumin from curcumin-loaded PLA fibers was investigated in phosphate buffer saline (PBS) containing ethanol. After 24 h, 50% of the curcumin was released from curcumin-loaded PLA fibers. These results of electrospun (e-spun) fibers exhibit the potential for biomedical application.
Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin.

PubMed

Lu, Qi; Ye, Fang; Yang, Xiangjun; Gu, Qingqing; Wang, Peng; Zhu, Jianhua; Shen, Li; Gong, Feirong

2015-01-01

Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP) has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents.
A Computational Architecture for Programmable Automation Research

NASA Astrophysics Data System (ADS)

Taylor, Russell H.; Korein, James U.; Maier, Georg E.; Durfee, Lawrence F.

1987-03-01

This short paper describes recent work at the IBM T. J. Watson Research Center directed at developing a highly flexible computational architecture for research on sensor-based programmable automation. The system described here has been designed with a focus on dynamic configurability, layered user inter-faces and incorporation of sensor-based real time operations into new commands. It is these features which distinguish it from earlier work. The system is cur-rently being implemented at IBM for research purposes and internal use and is an outgrowth of programmable automation research which has been ongoing since 1972 [e.g., 1, 2, 3, 4, 5, 6] .
Characterization and quantification of flavonoids and hydroxycinnamic acids in curly kale (Brassica oleracea L. Convar. acephala Var. sabellica) by HPLC-DAD-ESI-MSn.

PubMed

Olsen, Helle; Aaby, Kjersti; Borge, Grethe Iren A

2009-04-08

Kale is a leafy green vegetable belonging to the Brassicaceae family, a group of vegetables including cabbage, broccoli, cauliflower, and Brussels sprouts, with a high content of health-promoting phytochemicals. The flavonoids and hydroxycinammic acids of curly kale ( Brassica oleracea L. ssp. oleracea convar. acephala (DC.) Alef. var. sabellica L.), a variety of kale, were characterized and identified primarily through HPLC-DAD-ESI-MS(n) analysis. Thirty-two phenolic compounds including glycosides of quercetin and kaempferol and derivatives of p-coumaric, ferulic, sinapic, and caffeic acid were tentatively identified, providing a more complete identification of phenolic compounds in curly kale than previously reported. Moreover, three hydroxycinnamic acids and one flavonoid with an unusual high grade of glycosylation, quercetin-3-disinapoyl-triglucoside-7-diglucoside, have been tentatively identified for the first time. The influence of different extraction conditions (extraction method, solvent type, solvent/solid ratio, and duration of extraction) was investigated. The total flavonol and hydroxycinnamic acid contents in curly kale determined as rutin equivalents (RE) were 646 and 204 mg of RE/100 g of fresh weight (fw), respectively. The contents of individual flavonoids ranged from 2 to 159 mg of RE/100 g of fw, with main compounds kaempferol-3-sinapoyl-diglucoside-7-diglucoside (18.7%) and quercetin-3-sinapoyl-diglucoside-7-diglucoside (16.5%). After acidic hydrolysis, two flavonol aglycones were identified in curly kale, quercetin and kaempferol, with total contents of 44 and 58 mg/100 g of fw, respectively.
Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson's Disease.

PubMed

Pandareesh, M D; Shrivash, M K; Naveen Kumar, H N; Misra, K; Srinivas Bharath, M M

2016-11-01

Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.
Value-based medicine, comparative effectiveness, and cost-effectiveness analysis of topical cyclosporine for the treatment of dry eye syndrome.

PubMed

Brown, Melissa M; Brown, Gary C; Brown, Heidi C; Peet, Jonathan; Roth, Zachary

2009-02-01

To assess the comparative effectiveness and cost-effectiveness (cost-utility) of a 0.05% emulsion of topical cyclosporine (Restasis; Allergan Inc, Irvine, California) for the treatment of moderate to severe dry eye syndrome that is unresponsive to conventional therapy. Data from 2 multicenter, randomized, clinical trials and Food and Drug Administration files for topical cyclosporine, 0.05%, emulsion were used in Center for Value-Based Medicine analyses. Analyses included value-based medicine as a comparative effectiveness analysis and average cost-utility analysis using societal and third-party insurer cost perspectives. Outcome measures of comparative effectiveness were quality-adjusted life-year (QALY) gain and percentage of improvement in quality of life, and for cost-effectiveness were cost-utility ratio (CUR) using dollars per QALY. Topical cyclosporine, 0.05%, confers a value gain (comparative effectiveness) of 0.0319 QALY per year compared with topical lubricant therapy, a 4.3% improvement in quality of life for the average patient with moderate to severe dry eye syndrome that is unresponsive to conventional lubricant therapy. The societal perspective incremental CUR for cyclosporine over vehicle therapy is $34,953 per QALY and the societal perspective average CUR is $11,199 per QALY. The third-party-insurer incremental CUR is $37,179 per QALY, while the third-party-insurer perspective average CUR is $34,343 per QALY. Topical cyclosporine emulsion, 0.05%, confers considerable patient value and is a cost-effective therapy for moderate to severe dry eye syndrome that is unresponsive to conventional therapy.
Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles.

PubMed

Chuah, Lay Hong; Roberts, Clive J; Billa, Nashiru; Abdullah, Syahril; Rosli, Rozita

2014-04-01

Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer. Copyright © 2014 Elsevier B.V. All rights reserved.
Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine.

PubMed

Zhao, Jiaojiao; Pan, Yuchen; Li, Xiujun; Zhang, Xuefang; Xue, Yaxian; Wang, Tingting; Zhao, Shuli; Hou, Yayi

2017-01-01

Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3'-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.
Non-labeled quantitative proteomic comparison identifies differences in acid resistance between Escherichia coli O157:H7 curli production variants

USDA-ARS?s Scientific Manuscript database

To understand the nature and capability of a bacterial strain to tolerate environmental conditions it is necessary to be able to identify and measure the proteins that they are expressing in any given situation. In this research, the entire protein complements produced by Escherichia coli O157:H7 s...
Composition of lactic acid bacteria during spontaneous curly kale (Brassica oleracea var. sabellica) fermentation.

PubMed

Michalak, Magdalena; Gustaw, Klaudia; Waśko, Adam; Polak-Berecka, Magdalena

2018-01-01

The present work is the first report on spontaneous fermentation of curly kale and characteristics of autochthonous lactic acid bacteria (LAB). Our results indicate that curly kale fermentation is the new possibility of the technological use of this vegetable. Bacteria representing ten different species were isolated from three phases of curly kale fermentation and identified by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. Among them, four species were identified as Lactobacillus spp. (Lb. plantarum 332, Lb. paraplantarum G2114, Lb. brevis R413, Lb. curvatus 154), two as Weissella spp. (W. hellenica 152, W. cibaria G44), two as Pediococcus spp. (P. pentosaceus 45AN, P. acidilactici 2211), one as Leuconostoc mesenteroides 153, and one as Lactococcus lactis 37BN. The functional properties of isolates, i.e. acid, NaCl and bile salt tolerance, enzyme activities, adhesion to hydrocarbons, and antibiotic resistance, were examined. Among the tested strains, Lb. plantarum 332, Lb. paraplantarum G2114, P. pentosaceus 2211, and Lb. brevis R413 exhibited the best hydrophobicity value and high tolerance to bile salts, NaCl, and low pH. Copyright © 2017 Elsevier GmbH. All rights reserved.
Bacillus spore-based oral carriers loading curcumin for the therapy of colon cancer.

PubMed

Yin, Liang; Meng, Zhan; Zhang, Yuxiao; Hu, Kaikai; Chen, Wuya; Han, Kaibin; Wu, Bao-Yan; You, Rong; Li, Chu-Hua; Jin, Ying; Guan, Yan-Qing

2018-02-10

Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer. Copyright © 2017 Elsevier B.V. All rights reserved.
Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs.

PubMed

McCubrey, James A; Lertpiriyapong, Kvin; Steelman, Linda S; Abrams, Steve L; Yang, Li V; Murata, Ramiro M; Rosalen, Pedro L; Scalisi, Aurora; Neri, Luca M; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

2017-06-12

Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric ( Curcuma longa ). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants ( e.g., Coptis chinensis ) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.

Alginate-Based Composite Sponges as Gastroretentive Carriers for Curcumin-Loaded Self-Microemulsifying Drug Delivery Systems

PubMed Central

Petchsomrit, Arpa; Sermkaew, Namfa; Wiwattanapatapee, Ruedeekorn

2017-01-01

Alginate-based composite sponges were developed as carriers to prolong the gastric retention time and controlled release of curcumin-loaded self-microemulsifying drug delivery systems (Cur-SMEDDS). Liquid Cur-SMEDDS was incorporated into a solution made up of a mixture of polymers and converted into a solid form by freeze-drying. The ratio of alginate as the main polymer, adsorbent (colloidal silicon dioxide), and additional polymers—sodium carboxymethyl cellulose (SCMC), hydroxypropyl methylcellulose (HPMC)—was varied systematically to adjust the drug loading and entrapment efficiency, sponge buoyancy, and the release profile of Cur-SMEDDS. The optimum composite sponge was fabricated from a 4% alginate and 2% HPMC mixed solution. It immediately floated on simulated gastric fluid (SGF, pH 1.2) and remained buoyant over an 8 h period. The formulation exhibited an emulsion droplet size of approximately 30 nm and provided sustained release of Cur-SMEDDS in SGF, reaching 71% within 8 h compared with only 10% release from curcumin powder. This study demonstrates the potential of alginate-based composite sponges combined with self-microemulsifying formulations for gastroretention applications involving poorly soluble compounds. PMID:28294964
Experimental Detection and Visualization of the Extracellular Matrix in Macrocolony Biofilms.

PubMed

Serra, Diego O; Hengge, Regine

2017-01-01

By adopting elaborate three-dimensional morphologies that vary according to their extracellular matrix composition, macrocolony biofilms offer a unique opportunity to interrogate about the roles of specific matrix components in shaping biofilm architecture. Here, we describe two methods optimized for Escherichia coli that profit from morphology and the high level of structural organization of macrocolonies to gain insight into the production and assembly of amyloid curli and cellulose-the two major biofilm matrix elements of E. coli-in biofilms. The first method, the macrocolony morphology assay, is based on the ability of curli and cellulose-either alone or in combination-to generate specific morphological and Congo Red-staining patterns in E. coli macrocolonies, which can then be used as a direct visual readout for the production of these matrix components. The second method involves thin sectioning of macrocolonies, which along with in situ staining of amyloid curli and cellulose and microscopic imaging allows gaining fine details of the spatial arrangement of both matrix elements inside macrocolonies. Beyond their current use with E. coli and related curli and cellulose-producing Enterobacteriaceae, both the methods offer the potential to be adapted to other bacterial species.
Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

PubMed Central

McCubrey, James A.; Lertpiriyapong, Kvin; Steelman, Linda S.; Abrams, Steve L.; Yang, Li V.; Murata, Ramiro M.; Rosalen, Pedro L.; Scalisi, Aurora; Neri, Luca M.; Cocco, Lucio; Ratti, Stefano; Martelli, Alberto M.; Laidler, Piotr; Dulińska-Litewka, Joanna; Rakus, Dariusz; Gizak, Agnieszka; Lombardi, Paolo; Nicoletti, Ferdinando; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre

2017-01-01

Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health. PMID:28611316
Chronic urinary retention in men: how we define it, and how does it affect treatment outcome.

PubMed

Negro, Carlo L A; Muir, Gordon H

2012-12-01

What's known on the subject? and What does the study add? Chronic urinary retention (CUR) is a poorly defined entity, as the key element of definition, significant postvoid residual urine volume (PVR), has not a worldwide and moreover evidenced-based definition. There is no agreement on which is the threshold value to define a significant PVR and different society produced guidelines with different thresholds ranging from 300 mL to 1000 mL. Diagnosis is difficult, and management has not been defined yet. There is a lack of studies on the best management of these patients, as this group of patients has always been considered at high risk of failure. Only one study compares conservative with the surgical management but it is not a randomised controlled trail. This review offers a systematic appraisal of the most recent publications on CUR. It indicates the absence of a real worldwide agreed definition, as the two keys element of it are not satisfactorily defined yet: significant PVR, is suffering from a lack of evidenced-based definition, and percussable or palpable bladder is a very nebulous concept as it is not a criteria of certainty as different individual variables affect it. This has an important effect on management which is not structured. Most of the trials involving benign prostatic hyperplasia treatments (either medical or surgical) tend to exclude this group of patients, which is a clinically important group, comprising up to a quarter of men undergoing TURP in the UK. Urinary retention describes a bladder that does not empty completely or does not empty at all. Historically, urinary retention has been classified as either acute or chronic the latter is generally classified as high pressure or low pressure according to the bladder filling pressure on urodynamic. A MEDLINE® search for articles written in English and published before January 2010 was done using a list of terms related to urinary retention: 'urinary retention', 'chronic urinary retention' and 'PVR'. Chronic urinary retention (CUR) is defined by the International Continence Society as 'a non-painful bladder, which remains palpable or percussable after the patient has passed urine'. Abrams was the first to choose a residual urine volume >300 mL to define CUR as he considered it the minimum volume at which the bladder becomes palpable suprapubically. The UK National Institute for Health and Clinical Excellence lower urinary tract symptoms (LUTS) guidelines define CUR as a postvoid residual urine volume (PVR) of >1000 mL. No studies have specifically addressed the problem of quantifying the minimum amount of urine present in the bladder to define CUR. Nor did we find any publications objectively assessing at what amount of urine a bladder can be palpable. The ability to feel a bladder may rely on variables (i.e. medical skills and patient habitus). There is a marked variability of PVR, so the test should be repeated to improve precision. As defining CUR is difficult, structured management is challenging. Nearly all prospective trials exclude men with CUR from analysis, possibly anticipating a poor outcome and a high risk of complications. However, men with CUR are a clinically important group, comprising up to 25% of men undergoing transurethral resection of the prostate. Definition of CUR is imprecise and arbitrary. Most studies seem to describe the condition as either a PVR of >300 mL in men who are voiding, or >1000 mL in men who are unable to void. This confusion leads to an inability to design and interpret studies; indeed most prospective trials simply exclude these patients. There is a clear need for internationally accepted definitions of retention to allow both treatment and reporting of outcomes in men with LUTS, and for such definitions to be used by all investigators in future trials. © 2012 BJU INTERNATIONAL.
Effect of concentration of Curcuma longa L. on chitosan-starch based edible coating

NASA Astrophysics Data System (ADS)

Yusof, N. M.; Jai, J.; Hamzah, F.; Yahya, A.; Pinijsuwan, S.

2017-08-01

The ability of chitosan-starch based coating to extend shelf life of strawberry were studied. The main objectives of this paper is to study the effects of different concentrations (20, 15, 10 and 5 µL) of Curcuma longa L. (CUR) essential oil into chitosan-based edible coating on surface tension in order to increase the effectiveness of the coating. CUR or turmeric is one of the commercially planted herbs in Malaysia for its phytochemical benefits. Application of edible coating using dipping technique has been analysed and evaluated for their effectiveness in extending shelf life of fruits. Surface tension was analysed to investigate the adhesion properties. The best CUR concentration was 15 µL with the optimum surface tension was found to be 31.92 dynes/cm.
The undergraduate-postgraduate-faculty triad: unique functions and tensions associated with undergraduate research experiences at research universities.

PubMed

Dolan, Erin L; Johnson, Deborah

2010-01-01

We present an exploratory study of how undergraduates' involvement in research influences postgraduates (i.e., graduate and postdoctoral researchers) and faculty. We used a qualitative approach to examine the relationships among undergraduates, postgraduates, and the faculty head in a research group. In this group, undergraduates viewed postgraduates as more approachable than the faculty head both literally and figuratively. Mentorship by postgraduates presented unique challenges for undergraduates, including unrealistic expectations and varying abilities to mentor. The postgraduates and faculty head concurred that undergraduates contributed to the group's success and served as a source of frustration. Postgraduates appreciated the opportunity to observe multiple approaches to mentoring as they saw the faculty head and other postgraduates interact with undergraduates. The faculty head viewed undergraduate research as important for propagating the research community and for gaining insights into undergraduates and their postgraduate mentors. These results highlight how the involvement of undergraduates and postgraduates in research can limit and enhance the research experiences of members of the undergraduate-postgraduate-faculty triad. A number of tensions emerge that we hypothesize are intrinsic to undergraduate research experiences at research universities. Future studies can focus on determining the generalizability of these findings to other groups and disciplines.
Effects of cell surface characteristics and manure-application practices on Escherichia coli populations in the subsurface: A three-farm study

NASA Astrophysics Data System (ADS)

Salvucci, A. E.; Elton, M.; Siler, J. D.; Zhang, W.; Richards, B. K.; Geohring, L. D.; Warnick, L. D.; Hay, A. G.; Steenhuis, T.

2010-12-01

The introduction of microbial pathogens into the environment from untreated manure represents a threat to water quality and human health. Thus, understanding the effect of manure management strategies is imperative to effectively mitigate the inadvertent release of pathogens, particularly in subsurface environments where they can be transported through macropores to the groundwater or through agricultural tile line to open water bodies. The production of cell-surface biomolecules is also suspected to play an important role in the environmental survival and transport of enterobacterial pathogens. This study collected Escherichia coli samples from three dairy farms with artificial tile drainage systems and active manure spreading in the Central New York region over a three-month period. Sampling targeted four potential source locations on each farm: (i) cow housing, (ii) manure storage facilities, (iii) field soil, and (iv) subsurface drainage effluent. Over 2800 E. coli isolates were recovered and consequently analyzed for the cell surface components, cellulose and curli, traits associated with increased environmental survival, altered transport and pathogenicity. The E. coli isolates from locations i-iii displayed highly variable curli and cellulose-producing communities, while isolates collected from subsurface runoff on each farm had stable curli and cellulose production communities over all sampling dates. Furthermore, the method of manure application to the fields influenced the population characteristics found in drainage effluent isolates. Incorporation of manure into the soil was correlated to isolate populations largely deficient of curli and cellulose; whereas farms that only surface-applied manure were correlated to isolate populations of high curli and cellulose production. The production of curli and cellulose has previously been shown to be a response to environmental stress on the cell. Therefore, incorporation of manure directly into the soil appears to minimize environmental stresses, like UV radiation, desiccation and temperature fluctuation, typically found on the soil surface. Our findings indicate that E. coli strains above the surface are largely diverse, until they enter subsurface environments where specific extracellular characteristics are likely advantageous for survival and/or transport.
A two-step synthetic strategy to obtain a water-soluble derivative of curcumin with improved antioxidant capacity and in vitro cytotoxicity in C6 glioma cells.

PubMed

Landeros, José M; Belmont-Bernal, Fernando; Pérez-González, Alma Teresa; Pérez-Padrón, Mario Israel; Guevara-Salazar, Patricia; González-Herrera, Irma Gabriela; Guadarrama, Patricia

2017-02-01

A novel water-soluble derivative of curcumin (Cur-[G-2]-OH) was designed and synthesized from accessible raw materials in only two steps with an overall yield of 80%. The modification of curcumin phenol groups with second-generation polyester dendrons (dendronization) as a strategy to achieve an optimal hydrophilic/hydrophobic balance allows the complete water solubilization of the new curcumin derivative (5mg/ml) at room temperature. The therapeutic potential of Cur-[G-2]-OH was investigated in terms of antioxidant capacity, intracellular uptake and cytotoxicity in both rat glioblastoma cells and normal human dermal fibroblasts. Although the phenolic groups of curcumin were locked by dendronization, Cur-[G-2]-OH exhibited antioxidant capacity in water that was even higher than curcumin in dimethylsulfoxide (DMSO). This compound showed a steady cellular uptake contrasted with curcumin, which has a saturation capture at high concentrations. Combined with improved stability, this property seems to allow the intracellular accumulation of Cur-[G-2]-OH. Furthermore, the new compound exhibited increased cytotoxicity in rat C6 glioma cells in a time- and concentration-dependent manner, whereas in normal human fibroblasts, its IC 50 value was >600μM versus the IC 50 of curcumin found between 100 and 200μM. Surprisingly, Cur-[G-2]-OH drives cell death of C6 cells by a different mechanism of apoptosis triggered by curcumin. Together, these results suggest that curcumin dendronization could promote molecular and cellular mechanisms that are different from those induced by curcumin, presumably due to structural factors and not only for improved water solubility. Copyright © 2016 Elsevier B.V. All rights reserved.
Role of an archaeal PitA transporter in the copper and arsenic resistance of Metallosphaera sedula, an extreme thermoacidophile.

PubMed

McCarthy, Samuel; Ai, Chenbing; Wheaton, Garrett; Tevatia, Rahul; Eckrich, Valerie; Kelly, Robert; Blum, Paul

2014-10-01

Thermoacidophilic archaea, such as Metallosphaera sedula, are lithoautotrophs that occupy metal-rich environments. In previous studies, an M. sedula mutant lacking the primary copper efflux transporter, CopA, became copper sensitive. In contrast, the basis for supranormal copper resistance remained unclear in the spontaneous M. sedula mutant, CuR1. Here, transcriptomic analysis of copper-shocked cultures indicated that CuR1 had a unique regulatory response to metal challenge corresponding to the upregulation of 55 genes. Genome resequencing identified 17 confirmed mutations unique to CuR1 that were likely to change gene function. Of these, 12 mapped to genes with annotated function associated with transcription, metabolism, or transport. These mutations included 7 nonsynonymous substitutions, 4 insertions, and 1 deletion. One of the insertion mutations mapped to pseudogene Msed_1517 and extended its reading frame an additional 209 amino acids. The extended mutant allele was identified as a homolog of Pho4, a family of phosphate symporters that includes the bacterial PitA proteins. Orthologs of this allele were apparent in related extremely thermoacidophilic species, suggesting M. sedula naturally lacked this gene. Phosphate transport studies combined with physiologic analysis demonstrated M. sedula PitA was a low-affinity, high-velocity secondary transporter implicated in copper resistance and arsenate sensitivity. Genetic analysis demonstrated that spontaneous arsenate-resistant mutants derived from CuR1 all underwent mutation in pitA and nonselectively became copper sensitive. Taken together, these results point to archaeal PitA as a key requirement for the increased metal resistance of strain CuR1 and its accelerated capacity for copper bioleaching. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Role of an Archaeal PitA Transporter in the Copper and Arsenic Resistance of Metallosphaera sedula, an Extreme Thermoacidophile

PubMed Central

McCarthy, Samuel; Ai, Chenbing; Wheaton, Garrett; Tevatia, Rahul; Eckrich, Valerie; Kelly, Robert

2014-01-01

Thermoacidophilic archaea, such as Metallosphaera sedula, are lithoautotrophs that occupy metal-rich environments. In previous studies, an M. sedula mutant lacking the primary copper efflux transporter, CopA, became copper sensitive. In contrast, the basis for supranormal copper resistance remained unclear in the spontaneous M. sedula mutant, CuR1. Here, transcriptomic analysis of copper-shocked cultures indicated that CuR1 had a unique regulatory response to metal challenge corresponding to the upregulation of 55 genes. Genome resequencing identified 17 confirmed mutations unique to CuR1 that were likely to change gene function. Of these, 12 mapped to genes with annotated function associated with transcription, metabolism, or transport. These mutations included 7 nonsynonymous substitutions, 4 insertions, and 1 deletion. One of the insertion mutations mapped to pseudogene Msed_1517 and extended its reading frame an additional 209 amino acids. The extended mutant allele was identified as a homolog of Pho4, a family of phosphate symporters that includes the bacterial PitA proteins. Orthologs of this allele were apparent in related extremely thermoacidophilic species, suggesting M. sedula naturally lacked this gene. Phosphate transport studies combined with physiologic analysis demonstrated M. sedula PitA was a low-affinity, high-velocity secondary transporter implicated in copper resistance and arsenate sensitivity. Genetic analysis demonstrated that spontaneous arsenate-resistant mutants derived from CuR1 all underwent mutation in pitA and nonselectively became copper sensitive. Taken together, these results point to archaeal PitA as a key requirement for the increased metal resistance of strain CuR1 and its accelerated capacity for copper bioleaching. PMID:25092032
Roles of curli, cellulose and BapA in Salmonella biofilm morphology studied by atomic force microscopy.

PubMed

Jonas, Kristina; Tomenius, Henrik; Kader, Abdul; Normark, Staffan; Römling, Ute; Belova, Lyubov M; Melefors, Ojar

2007-07-24

Curli, cellulose and the cell surface protein BapA are matrix components in Salmonella biofilms. In this study we have investigated the roles of these components for the morphology of bacteria grown as colonies on agar plates and within a biofilm on submerged mica surfaces by applying atomic force microscopy (AFM) and light microscopy. AFM imaging was performed on colonies of Salmonella Typhimurium grown on agar plates for 24 h and on biofilms grown for 4, 8, 16 or 24 h on mica slides submerged in standing cultures. Our data show that in the wild type curli were visible as extracellular material on and between the cells and as fimbrial structures at the edges of biofilms grown for 16 h and 24 h. In contrast to the wild type, which formed a three-dimensional biofilm within 24 h, a curli mutant and a strain mutated in the global regulator CsgD were severely impaired in biofilm formation. A mutant in cellulose production retained some capability to form cell aggregates, but not a confluent biofilm. Extracellular matrix was observed in this mutant to almost the same extent as in the wild type. Overexpression of CsgD led to a much thicker and a more rapidly growing biofilm. Disruption of BapA altered neither colony and biofilm morphology nor the ability to form a biofilm within 24 h on the submerged surfaces. Besides curli, the expression of flagella and pili as well as changes in cell shape and cell size could be monitored in the growing biofilms. Our work demonstrates that atomic force microscopy can efficiently be used as a tool to monitor the morphology of bacteria grown as colonies on agar plates or within biofilms formed in a liquid at high resolution.
Comparative analysis of protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle and nanoliposomal curcumin on unsymmetrical dimethyl hydrazine poisoning in mice

PubMed Central

Li, Wei; Zhou, Mengzhou; Xu, Ning; Hu, Yong; Wang, Chao; Li, Deyuan; Liu, Liegang; Li, Dongsheng

2016-01-01

ABSTRACT The aim of this study was to compare the protective effects of curcumin, curcumin-β-cyclodextrin nanoparticle curcumin (BCD-CUR) and nanoliposomal curcumin (NLC) on unsymmetrical dimethylhydrazine (UDMH) induced poison in mice. Curcumin, BCD-CUR, and NLC were prepared and their properties of zeta potential, particle size, encapsulation efficiency, and loading capacity were characterized. Eighty-eight male ICR mice on normal chow diet were randomly divided into 11 groups, and intraperitoneally injected with UDMH alone, or together with different doses of curcumin, BCD-CUR or NLC daily for up to 10 d. Enzyme activities of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were analyzed by fully-automatic analyzer and neurotransmitter levels were determined with high performance liquid chromatography (HPLC). 150 mg/kg curcumin treatment alone significantly reduced levels of serum ALT and LDH that were induced by UDMH and markedly increased level of γ-amino butyric acid (GABA) that were reduced by UDMH in the hippocampus. 150 mg/kg BCD-CUR not only decreased significantly the increase of ALT, LDH and glutamate (Glu) but also recovered levels of AST and GABA. 150 mg/kg NLC recovered profoundly levels of AST and GABA while decreased remarkably the UDMH induced increase of ALT, LDH, Glu and 5-hydroxytryptamine (5-HT). In addition, treatments with all tested doses of NLC significantly reduced the UMDH induced dopamine (DA), the monoamine neurotransmitter. NLC had more profound protective effects against liver and central nervous system injury induced by UDMH than a suspension of BCD-CUR or curcumin did in mice. PMID:27710431
Smart Drug Delivery System-Inspired Enzyme-Linked Immunosorbent Assay Based on Fluorescence Resonance Energy Transfer and Allochroic Effect Induced Dual-Modal Colorimetric and Fluorescent Detection.

PubMed

Miao, Luyang; Zhu, Chengzhou; Jiao, Lei; Li, He; Du, Dan; Lin, Yuehe; Wei, Qin

2018-02-06

Numerous analytical techniques have been undertaken for the detection of protein biomarkers because of their extensive and significant applications in clinical diagnosis, whereas there are few strategies to develop dual-readout immunosensors to achieve more accurate results. To the best of our knowledge, inspired by smart drug delivery system (DDS), a novel pH-responsive modified enzyme-linked immunosorbent assay (ELISA) was innovatively developed for the first time, realizing dual-modal colorimetric and fluorescent detection of cardiac troponin I (cTnI). Curcumin (CUR) was elaborately selected as a reporter molecule, which played the same role of drugs in DDS based on the following considerations: (1) CUR can be used as a kind of pH indicator by the inherited allochroic effect induced by basic pH value; (2) the fluorescence of CUR can be quenched by certain nanocarriers as the acceptor because of the occurrence of fluorescence resonance energy transfer (FRET), while recovered by the stimuli of basic pH value, which can produce "signal-on" fluorescence detection. Three-dimensional MoS 2 nanoflowers (3D-MoS 2 NFs) were employed in immobilizing CUR to constitute a nanoprobe for the determination of cTnI by virtue of good biocompatibility, high absorption capacity, and fluorescence quench efficiency toward CUR. The proposed DDS-inspired ELISA offered dual-modal colorimetric and fluorescent detection of cTnI, thereby meeting the reliable and precise analysis requirements. We believe that the developed dual-readout ELISA will create a new avenue and bring innovative inspirations for biological detections.
Curli mediate bacterial adhesion to fibronectin via tensile multiple bonds

NASA Astrophysics Data System (ADS)

Oh, Yoo Jin; Hubauer-Brenner, Michael; Gruber, Hermann J.; Cui, Yidan; Traxler, Lukas; Siligan, Christine; Park, Sungsu; Hinterdorfer, Peter

2016-09-01

Many enteric bacteria including pathogenic Escherichia coli and Salmonella strains produce curli fibers that bind to host surfaces, leading to bacterial internalization into host cells. By using a nanomechanical force-sensing approach, we obtained real-time information about the distribution of molecular bonds involved in the adhesion of curliated bacteria to fibronectin. We found that curliated E. coli and fibronectin formed dense quantized and multiple specific bonds with high tensile strength, resulting in tight bacterial binding. Nanomechanical recognition measurements revealed that approximately 10 bonds were disrupted either sequentially or simultaneously under force load. Thus the curli formation of bacterial surfaces leads to multi-bond structural components of fibrous nature, which may explain the strong mechanical binding of curliated bacteria to host cells and unveil the functions of these proteins in bacterial internalization and invasion.
Directly solar-pumped iodine laser for beamed power transmission in space

NASA Technical Reports Server (NTRS)

Choi, S. H.; Meador, W. E.; Lee, J. H.

1992-01-01

A new approach for development of a 50-kW directly solar-pumped iodine laser (DSPIL) system as a space-based power station was made using a confocal unstable resonator (CUR). The CUR-based DSPIL has advantages, such as performance enhancement, reduction of total mass, and simplicity which alleviates the complexities inherent in the previous system, master oscillator/power amplifier (MOPA) configurations. In this design, a single CUR-based DSPIL with 50-kW output power was defined and compared to the MOPA-based DSPIL. Integration of multiple modules for power requirements more than 50-kW is physically and structurally a sound approach as compared to building a single large system. An integrated system of multiple modules can respond to various mission power requirements by combining and aiming the coherent beams at the user's receiver.
Undergraduate Research Participation at the University of California, Berkeley. Research & Occasional Paper Series: CSHE.17.08

ERIC Educational Resources Information Center

Berkes, Elizabeth

2008-01-01

Although the University of California, Berkeley has increased efforts to involve undergraduates in scientific research, little data exists regarding the number of undergraduate researchers. The University of California Undergraduate Experience Survey (UCUES) presents an opportunity to investigate the extent of undergraduate research involvement at…
Medical Surveillance Monthly Report (MSMR). Volume 5, Number 4, May 1999

DTIC Science & Technology

1999-05-01

Reporting Chlamydia Urethritis non-spec. Gonorrhea Syphilis Prim/Sec Syphilis Latent Syphilis Tertiary Syphilis Congenital MTF/Post** Cur. Cum. Cur. Cum...is prepared by the Army Medical Surveillance Activity , Directorate of Epidemiology and Disease Surveillance, United States Army Center for Health...Outbreak investigation: During the period 4 March to 8 April 1999, an Epidemiologic Consulta- tion (EPICON) team from the US Army Center for Health
Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4

PubMed Central

Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

2014-01-01

In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)—producing the biofilm-promoting second messenger c-di-GMP—that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. PMID:25361688
Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes.

PubMed

Mathy-Hartert, M; Jacquemond-Collet, I; Priem, F; Sanchez, C; Lambert, C; Henrotin, Y

2009-12-01

This study aims to investigate the effects of curcumin (Cur) on the extracellular matrix protein metabolism of articular chondrocytes and on their production of inflammatory mediators. Human chondrocytes in alginate beads and human cartilage explants were cultured in the absence or in the presence of interleukin (IL)-1beta (10(-11) M) and with or without Cur (5-20 microM). Nitric oxide (NO) synthesis was measured by the Griess spectrophotometric method; prostaglandin (PG) E(2) by a specific radioimmunoassay; and IL-6, IL-8, aggrecan (Agg), matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 by specific enzyme-amplified immunoassays. Proteoglycan degradation was evaluated by the release of (35)S-glycosaminoglycans (GAG) from human cartilage explants. In alginate beads and cartilage explant models, Cur inhibited the basal and the IL-1beta-stimulated NO, PGE(2), IL-6, IL-8, and MMP-3 production by human chondrocytes in a concentration-dependent manner. The TIMP-1 and the Agg productions were not modified. In the basal condition, (35)S-GAG release from cartilage explants was decreased by Cur. Curcumin was a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes, suggesting that this natural compound could be efficient in the treatment of osteoarthritis.
Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation.

PubMed

Cheung, Ka Lung; Khor, Tin Oo; Kong, Ah-Ng

2009-01-01

Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies. We used nitric oxide (NO) assay to assess the synergism of the different combinations of CUR, SFN and PEITC. The inflammatory markers, e.g. iNOS, COX-2, prostaglandin E2 (PGE2), tumor necrosis factor (TNF) and interleukin-1 (IL-1) levels were determined using RT-PCR, Western blot and ELISA assays. We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). Our data suggest that CUR + SFN and PEITC + SFN combinations could be more effective than used alone in preventing inflammation and possibly its associated diseases including cancer.

Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

PubMed

Wei, Xiao-Lan; Han, Ying-Rui; Quan, Li-Hui; Liu, Chun-Yu; Liao, Yong-Hong

2013-05-13

The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 μm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect. Copyright © 2013 Elsevier B.V. All rights reserved.
CRP: Collaborative Research Project (A Mathematical Research Experience for Undergraduates)

ERIC Educational Resources Information Center

Parsley, Jason; Rusinko, Joseph

2017-01-01

The "Collaborative Research Project" ("CRP")--a mathematics research experience for undergraduates--offers a large-scale collaborative experience in research for undergraduate students. CRP seeks to widen the audience of students who participate in undergraduate research in mathematics. In 2015, the inaugural CRP had 100…
The Impact of Army and Family Factors on Individual Readiness

DTIC Science & Technology

1993-08-01

families. While, in general , individual characteristics were more important in the determination of soldieL. readiness than famlily characteristics...affected indi- vidual readiness, in general , family-related variables had higher impact on soldier intention to remain in the Army after their cur- rent...installations. This survey was designed to provide information related to Army policy/program questions based on prior and current research anu to generate new
The United States Air Force Academy Solar Energy Research

DTIC Science & Technology

1980-07-01

controller, ir the solar sy .4tem, is malfunctioning. Put simply, the house will get cold. lf oh cUrs the occupant will notify civil engineering mainte...with this product has been Revere Copper Laminated Panel Sys - trial uses, condenser tubing, electrical of vital assistance in accumulating the tern...Laminated Panel require water temperatures near the additional components Include tubes,. Construction. In the Revere Panel Sys - boiling point,whereas
Impact of Forecast and Model Error Correlations In 4dvar Data Assimilation

NASA Astrophysics Data System (ADS)

Zupanski, M.; Zupanski, D.; Vukicevic, T.; Greenwald, T.; Eis, K.; Vonder Haar, T.

A weak-constraint 4DVAR data assimilation system has been developed at Cooper- ative Institute for Research in the Atmosphere (CIRA), Colorado State University. It is based on the NCEP's ETA 4DVAR system, and it is fully parallel (MPI coding). The CIRA's 4DVAR system is aimed for satellite data assimilation research, with cur- rent focus on assimilation of cloudy radiances and microwave satellite measurements. Most important improvement over the previous 4DVAR system is a degree of gener- ality introduced into the new algorithm, namely for applications with different NWP models (e.g., RAMS, WRF, ETA, etc.), and for the choice of control variable. In cur- rent applications, the non-hydrostatic RAMS model and its adjoint are used, including all microphysical processess. The control variable includes potential temperature, ve- locity potential and stream function, vertical velocity, and seven mixing ratios with respect to all water phases. Since the statistics of the microphysical components of the control variable is not well known, a special attention will be paid to the impact of the forecast and model (prior) error correlations on the 4DVAR analysis. In particular, the sensitivity of the analysis with respect to decorrelation length will be examined. The prior error covariances are modelled using the compactly-supported, space-limited correlations developed at NASA DAO.
The Relationship between Undergraduate Research Participation and Subsequent Research Performance of Early Career STEM Graduate Students

ERIC Educational Resources Information Center

Gilmore, Joanna; Vieyra, Michelle; Timmerman, Briana; Feldon, David; Maher, Michelle

2015-01-01

Undergraduate research experiences have been adopted across higher education institutions. However, most studies examining benefits derived from undergraduate research rely on self-report of skill development. This study used an empirical assessment of research skills to investigate associations between undergraduate research experiences and…
Research Experience for Undergraduate Students and Its Impact on STEM Education

ERIC Educational Resources Information Center

Zhan, Wei

2014-01-01

Research experience has been proven to be effective in enhancing the overall educational experience for undergraduate students. In this article, two engineering research projects with undergraduate students involvement are discussed. The projects provided the undergraduate student researchers with motivation for independent research work and…
Preparation and properties evaluation of a novel pH-sensitive liposomes based on imidazole-modified cholesterol derivatives.

PubMed

Ju, Liang; Cailin, Fang; Wenlan, Wu; Pinghua, Yu; Jiayu, Gao; Junbo, Li

2017-02-25

As a new kind of drug carries, pH-sensitive liposomes have been widely studied in tumor therapy for their advantages of target ability and sustained-release. Here, we synthesized a pH-sensitive material, N-(3-Aminopropyl)imidazole-cholesterol (IM-Chol) and prepared a novel pH-sensitive liposomes using IM-Chol and phosphatidylcholine. IM-Chol was synthesized through amidation reaction between the amino group of N-(3-Aminopropyl)imidazole and acyl chloride group of cholesteryl chloroformate in a weak base solution. Optimal conditions to prepare liposomes were obtained by the orthogonal experiment with the higher encapsulation efficiency as the evaluation indicator. The properties of liposomes, such as particle size, zeta potential, morphology, encapsulation efficiency, drug release behavior and in vitro cell toxicity were evaluated by transmission electron microscopy (TEM), dynamic light scattering (DLS) and MTT assay respectively. The results showed that the average particle size of IM-Chol liposomes was 141nm (PDI 0.323). Liposomes can assemble into uniform spheres at pH 7.4, but under the condition of pH 5.0, the spherical structure of IM-Chol liposomes was broken, exhibiting pH-sensitive property. In vitro drug releasing studies demonstrated the controlled-release behavior of the curcumin (CUR) in the IM-Chol liposomes. The cumulative release of CUR reached to 72.5% in the first 24h at pH 5.0, faster than that at pH 7.4, which confirmed that the drug carrier displayed pH-sensitive release behaviors. In addition, the MTT assay was employed to test the cytotoxicity of IM-Chol liposomes and CUR IM-Chol liposomes. All cell viabilities were greater than 80% after incubating for 24h, even up to the highest dose of 500mg/L, indicating that IM-Chol liposomes had good biocompatibility. The tumor inhibitory results towards EC109 cells of free CUR and CUR-loaded IM-Chol liposomes indicated that IM-Chol liposomes indeed enhanced the cell killing effect of CUR. These results showed that the novel IM-Chol liposomes prepared in this paper had pH-sensitive property and were expected to play a huge potential in tumor treatment. Copyright © 2016 Elsevier B.V. All rights reserved.
Group-effort Applied Research: Expanding Opportunities for Undergraduate Research through Original, Class-Based Research Projects

ERIC Educational Resources Information Center

Moore, Sean D.; Teter, Ken

2014-01-01

Undergraduate research clearly enriches the educational development of participating students, but these experiences are limited by the inherent inefficiency of the standard one student-one mentor model for undergraduate research. Group-effort applied research (GEAR) was developed as a strategy to provide substantial numbers of undergraduates with…
Developing Effective Undergraduate Research Experience

NASA Astrophysics Data System (ADS)

Evans, Michael; Ilie, Carolina C.

2011-03-01

Undergraduate research is a valuable educational tool for students pursuing a degree in physics, but these experiences can become problematic and ineffective if not handled properly. Undergraduate research should be planned as an immersive learning experience in which the student has the opportunity to develop his/her skills in accordance with their interests. Effective undergraduate research experiences are marked by clear, measurable objectives and frequent student-professor collaboration. These objectives should reflect the long and short-term goals of the individual undergraduates, with a heightened focus on developing research skills for future use. 1. Seymour, E., Hunter, A.-B., Laursen, S. L. and DeAntoni, T. (2004), ``Establishing the benefits of research experiences for undergraduates in the sciences: First findings from a three-year study''. Science Education, 88: 493--534. 2. Behar-Horenstein, Linda S., Johnson, Melissa L. ``Enticing Students to Enter Into Undergraduate Research: The Instrumentality of an Undergraduate Course.'' Journal of College Science Teaching 39.3 (2010): 62-70.
Toward a Holistic View of Undergraduate Research Experiences: An Exploratory Study of Impact on Graduate/Postdoctoral Mentors

ERIC Educational Resources Information Center

Dolan, Erin; Johnson, Deborah

2009-01-01

Involvement in research has become a fixture in undergraduate science education across the United States. Graduate and postdoctoral students are often called upon to mentor undergraduates at research universities, yet mentoring relationships in undergraduate-graduate/postdoctoral student dyads and undergraduate-graduate/postdoctoral…
Disruption of rcsB by a duplicated sequence in a curli-producing Escherichia coli O157:H7 results in differential gene expression in relation to biofilm formation, stress responses, and metabolism

USDA-ARS?s Scientific Manuscript database

Background: Escherichia coli O157:H7 (O157) strain 86-24, linked to a 1986 disease outbreak, displays biofilm- and curli-negative phenotypes that are correlated with the lack of Congo red (CR) binding and formation of white colonies (CR negative) on a CR negative containing medium. However, on a CR ...
Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4.

PubMed

Richter, Anja M; Povolotsky, Tatyana L; Wieler, Lothar H; Hengge, Regine

2014-12-01

In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)--producing the biofilm-promoting second messenger c-di-GMP--that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c-di-GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.
Polychlorinated biphenyls in the surrounding of an e-waste recycling facility in North-Rhine Westphalia: Levels in plants and dusts, spatial distribution, homologue pattern and source identification using the combination of plants and wind direction data.

PubMed

Klees, Marcel; Hombrecher, Katja; Gladtke, Dieter

2017-12-15

During this study the occurrence of polychlorinated biphenyls (PCBs) in the surrounding of an e-waste recycling facility in North-Rhine Westphalia was analysed. PCB levels were analysed in curly kale, spruce needles, street dusts and dusts. Conspicuously high PCB concentrations in curly kale and spruce needles were found directly northwards of the industrial premises. Furthermore a concentration gradient originating from the industrial premises to the residential areas in direction southwest to northeast was evident. Homologue patterns of highly PCB contaminated dusts and street dusts were comparable to the homologue patterns of PCB in curly kale and spruce needles. This corroborates the suspicion that the activities at the e-waste recycling facility were responsible for the elevated PCB levels in curly kale and spruce needles. The utilization of multiple linear regression of wind direction data and analysed PCB concentrations in spruce needles proved that the e-waste recycling facility caused the PCB emissions to the surrounding. Additionally, this evaluation enabled the calculation of source specific accumulation constants for certain parts of the facility. Consequently the different facility parts contribute with different impacts to the PCB levels in bioindicators. Copyright © 2017 Elsevier B.V. All rights reserved.
Correcting Inconsistencies and Errors in Bacterial Genome Metadata Using an Automated Curation Tool in Excel (AutoCurE).

PubMed

Schmedes, Sarah E; King, Jonathan L; Budowle, Bruce

2015-01-01

Whole-genome data are invaluable for large-scale comparative genomic studies. Current sequencing technologies have made it feasible to sequence entire bacterial genomes with relative ease and time with a substantially reduced cost per nucleotide, hence cost per genome. More than 3,000 bacterial genomes have been sequenced and are available at the finished status. Publically available genomes can be readily downloaded; however, there are challenges to verify the specific supporting data contained within the download and to identify errors and inconsistencies that may be present within the organizational data content and metadata. AutoCurE, an automated tool for bacterial genome database curation in Excel, was developed to facilitate local database curation of supporting data that accompany downloaded genomes from the National Center for Biotechnology Information. AutoCurE provides an automated approach to curate local genomic databases by flagging inconsistencies or errors by comparing the downloaded supporting data to the genome reports to verify genome name, RefSeq accession numbers, the presence of archaea, BioProject/UIDs, and sequence file descriptions. Flags are generated for nine metadata fields if there are inconsistencies between the downloaded genomes and genomes reports and if erroneous or missing data are evident. AutoCurE is an easy-to-use tool for local database curation for large-scale genome data prior to downstream analyses.
A Modular Coassembly Approach to All-In-One Multifunctional Nanoplatform for Synergistic Codelivery of Doxorubicin and Curcumin

PubMed Central

Yang, Muyang; Yu, Lixia; Guo, Ruiwei; Dong, Anjie; Lin, Cunguo

2018-01-01

Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell. Herein, we developed a facile modular coassembly approach to construct an all-in-one multifunctional multidrug delivery system for the synergistic codelivery of doxorubicin (DOX, chemotherapeutic agent) and curcumin (CUR, MDR modulator). The acid-cleavable PEGylated polymeric prodrug (DOX-h-PCEC), tumor cell-specific targeting peptide (CRGDK-PEG-PCL), and natural chemosensitizer (CUR) were ratiometrically assembled into in one single nanocarrier (CUR/DOX-h-PCEC@CRGDK NPs). The resulting CUR/DOX-h-PCEC@CRGDK NPs exhibited several desirable characteristics, such as efficient and ratiometric drug loading, high hemodynamic stability and low drug leakage, tumor intracellular acid-triggered cleavage, and subsequent intracellular simultaneous drug corelease, which are expected to maximize a synergistic effect of chemotherapy and chemosensitization. Collectively, the multifunctional nanocarrier is feasible for the creation of a robust nanoplatform for targeted multidrug codelivery and efficient MDR modulation. PMID:29543780
Preparation, characterization and in vivo evaluation of curcumin self-nano phospholipid dispersion as an approach to enhance oral bioavailability.

PubMed

Allam, Ahmed N; Komeil, Ibrahim A; Fouda, Mohamed A; Abdallah, Ossama Y

2015-07-15

The aim of this study was to examine the efficacy of self-nano phospholipid dispersions (SNPDs) based on Phosal(®) to improve the oral bioavailability of curcumin (CUR). SNPDs were prepared with Phosal(®) 53 and Miglyol 812 at different surfactant ratio. Formulations were evaluated for particle size, polydispersity index, zeta potential, and robustness toward dilution, TEM as well as in vitro drug release. The in vivo oral absorption of selected formulations in comparison to drug suspension was evaluated in rats. Moreover, formulations were assessed for in vitro characteristic changes before and after storage. The SNPDs were miscible with water in any ratio and did not show any phase separation or drug precipitation. All the formulas were monodisperse with nano range size from 158±2.6 nm to 610±6.24 nm. They passed the pharmacopeial tolerance for CUR dissolution. No change in dissolution profile and physicochemical characteristics was detected after storage. CUR-SNPDs are found to be more bioavailable compared with suspension during an in vivo study in rats and in vitro release studies failed to imitate the in vivo conditions. These formulations might be new alternative carriers that enhance the oral bioavailability of poorly water-soluble molecules, such as CUR. Copyright © 2015 Elsevier B.V. All rights reserved.
Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

PubMed Central

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-01-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer. PMID:27324595
Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

NASA Astrophysics Data System (ADS)

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-06-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.
Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

PubMed

Fang, Jen-Hung; Chiu, Tsung-Lang; Huang, Wei-Chen; Lai, Yen-Ho; Hu, Shang-Hsiu; Chen, You-Yin; Chen, San-Yuan

2016-03-01

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conducting Mathematical Research with Undergraduates

ERIC Educational Resources Information Center

Roberts, Gareth E.

2013-01-01

The notion that undergraduates are capable of making profound and original contributions to mathematical research is rapidly gaining acceptance. Undergraduates bring their enthusiasm, creativity, curiosity, and perseverance to bona fide research problems. This article discusses some of the key issues concerning undergraduate mathematical research:…
Curcumin as fluorescent probe for directly monitoring in vitro uptake of curcumin combined paclitaxel loaded PLA-TPGS nanoparticles

NASA Astrophysics Data System (ADS)

Nguyen, Hoai Nam; Thu Ha, Phuong; Sao Nguyen, Anh; Nguyen, Dac Tu; Doan Do, Hai; Nguyen Thi, Quy; Nhung Hoang Thi, My

2016-06-01

Theranostics, which is the combination of both therapeutic and diagnostic capacities in one dose, is a promising tool for both clinical application and research. Although there are many chromophores available for optical imaging, their applications are limited due to the photobleaching property or intrinsic toxicity. Curcumin, a natural compound extracted from the rhizome of curcuma longa, is well known thanks to its bio-pharmaceutical activities and strong fluorescence as biocompatible probe for bio-imaging. In this study, we aimed to fabricate a system with dual functions: diagnostic and therapeutic, based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) micelles co-loaded curcumin (Cur) and paclitaxel (PTX). Two kinds of curcumin nanoparticle (NP) were fabricated and characterized by Fourier transform infrared spectroscopy, field emission scanning electron microscopy and dynamic light scattering methods. The cellular uptake and fluorescent activities of curcumin in these systems were also tested by bioassay studies, and were compared with paclitaxe-oregon. The results showed that (Cur + PTX)-PLA-TPGS NPs is a potential system for cancer theranostics.
The Potential to use Publication of Undergraduate Research as a Teaching Tool

NASA Astrophysics Data System (ADS)

Brevik, Eric C.; Lindbo, David L.; Belcher, Christopher

2015-04-01

Several studies crossing numerous disciplinary boundaries have demonstrated that undergraduate students benefit from research experiences. These benefits include personal and intellectual development, more and closer contact with faculty, the use of active learning techniques, the creation of high expectations, the development of creative and problem-solving skills, and the development of greater independence and intrinsic motivation to learn. The discipline also gains in that studies show undergraduates who engage in research experiences are more likely to remain science majors and finish their degree program. Research experiences come as close as possible to allowing undergraduates to experience what it is like to be an academic or research member of their profession working to advance their discipline, therefore enhancing their professional socialization into their chosen field. If the goals achieved by undergraduate research include introducing these students to the advancement of their chosen field, it stands to reason the ultimate ending to this experience would be the publication of a peer-reviewed paper. While not all undergraduate projects will end with a product worthy of peer-reviewed publication, some definitely do, and the personal experience of the authors indicates that undergraduate students who achieve publication get great satisfaction and a sense of personal achievement from that publication. While a top-tier international journal probably isn't going to be the ultimate destination for many of these projects, there are several appropriate outlets. The SSSA journal Soil Horizons has published several undergraduate projects in recent years, and good undergraduate projects can often be published in state academy of science journals. Journals focused expressly on publishing undergraduate research include the Journal of Undergraduate Research and Scholarly Excellence, Reinvention, and the American Journal of Undergraduate Research. Case studies of students who have published undergraduate research will be discussed.
A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate–Postgraduate–Faculty Triads

PubMed Central

Aikens, Melissa L.; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T.; Dolan, Erin L.

2016-01-01

Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as “postgraduates”) and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the undergraduate’s research. Using a social capital theory framework, we hypothesized that different triad structures provide undergraduates with varying resources (e.g., information, advice, psychosocial support) from the postgraduates and/or faculty, which would affect the undergraduates’ research outcomes. To test this, we collected data from a national sample of undergraduate life science researchers about their mentoring triad structure and a range of outcomes associated with research experiences, such as perceived gains in their abilities to think and work like scientists, science identity, and intentions to enroll in a PhD program. Undergraduates mentored by postgraduates alone reported positive outcomes, indicating that postgraduates can be effective mentors. However, undergraduates who interacted directly with faculty realized greater outcomes, suggesting that faculty interaction is important for undergraduates to realize the full benefits of research. The “closed triad,” in which undergraduates, postgraduates, and faculty all interact directly, appeared to be uniquely beneficial; these undergraduates reported the highest gains in thinking and working like a scientist. PMID:27174583
A Survey of Campus Coordinators of Undergraduate Research Programs

ERIC Educational Resources Information Center

Hensley, Merinda Kaye; Shreeves, Sarah L.; Davis-Kahl, Stephanie

2015-01-01

Interest in supporting undergraduate research programs continues to grow within academic librarianship. This article presents how undergraduate research program coordinators perceive and value library support of their programs. Undergraduate research coordinators from a variety of institutions were surveyed on which elements of libraries and…
Lasting Lessons: Following up with Recipients of the Forum's Undergraduate Research Award

ERIC Educational Resources Information Center

Forum on Education Abroad, 2012

2012-01-01

The annual Forum on Education Abroad Undergraduate Research Award showcases rigorous and significant undergraduate research that occurs as part of education abroad programs. Every year, the award recipients present their research at a plenary luncheon at the Forum's Annual Conference. The Forum granted the first Undergraduate Research Awards in…
Roles of curli, cellulose and BapA in Salmonella biofilm morphology studied by atomic force microscopy

PubMed Central

Jonas, Kristina; Tomenius, Henrik; Kader, Abdul; Normark, Staffan; Römling, Ute; Belova, Lyubov M; Melefors, Öjar

2007-01-01

Background Curli, cellulose and the cell surface protein BapA are matrix components in Salmonella biofilms. In this study we have investigated the roles of these components for the morphology of bacteria grown as colonies on agar plates and within a biofilm on submerged mica surfaces by applying atomic force microscopy (AFM) and light microscopy. Results AFM imaging was performed on colonies of Salmonella Typhimurium grown on agar plates for 24 h and on biofilms grown for 4, 8, 16 or 24 h on mica slides submerged in standing cultures. Our data show that in the wild type curli were visible as extracellular material on and between the cells and as fimbrial structures at the edges of biofilms grown for 16 h and 24 h. In contrast to the wild type, which formed a three-dimensional biofilm within 24 h, a curli mutant and a strain mutated in the global regulator CsgD were severely impaired in biofilm formation. A mutant in cellulose production retained some capability to form cell aggregates, but not a confluent biofilm. Extracellular matrix was observed in this mutant to almost the same extent as in the wild type. Overexpression of CsgD led to a much thicker and a more rapidly growing biofilm. Disruption of BapA altered neither colony and biofilm morphology nor the ability to form a biofilm within 24 h on the submerged surfaces. Besides curli, the expression of flagella and pili as well as changes in cell shape and cell size could be monitored in the growing biofilms. Conclusion Our work demonstrates that atomic force microscopy can efficiently be used as a tool to monitor the morphology of bacteria grown as colonies on agar plates or within biofilms formed in a liquid at high resolution. PMID:17650335
Hha Controls Escherichia coli O157:H7 Biofilm Formation by Differential Regulation of Global Transcriptional Regulators FlhDC and CsgD

PubMed Central

Bearson, Bradley L.

2013-01-01

Although molecular mechanisms promoting adherence of enterohemorrhagic Escherichia coli (EHEC) O157:H7 on epithelial cells are well characterized, regulatory mechanisms controlling biofilm formation are not fully understood. In this study, we demonstrate that biofilm formation in EHEC O157:H7 strain 86-24 is highly repressed compared to that in an isogenic hha mutant. The hha mutant produced large quantities of biofilm compared to the wild-type strain at 30°C and 37°C. Complementation of the hha mutant reduced the level of biofilm formation to that of the wild-type strain, indicating that Hha is a negative regulator of biofilm production. While swimming motility and expression of the flagellar gene fliC were significantly reduced, the expression of csgA (encoding curlin of curli fimbriae) and the ability to bind Congo red were significantly enhanced. The expression of both fliC and csgA and the phenotypes of motility and curli production affected by these two genes, respectively, were restored to wild-type levels in the complemented hha mutant. The csgA deletion abolished biofilm formation in the hha mutant and wild-type strain, and csgA complementation restored biofilm formation to these strains, indicating the importance of csgA and curli in biofilm formation. The regulatory effects of Hha on flagellar and curli gene expression appear to occur via the induction and repression of FlhDC and CsgD, as demonstrated by reduced flhD and increased csgD transcription in the hha mutant, respectively. In gel shift assays Hha interacted with flhDC and csgD promoters. In conclusion, Hha regulates biofilm formation in EHEC O157:H7 by differential regulation of FlhDC and CsgD, the global regulators of motility and curli production, respectively. PMID:23377937
Hha controls Escherichia coli O157:H7 biofilm formation by differential regulation of global transcriptional regulators FlhDC and CsgD.

PubMed

Sharma, Vijay K; Bearson, Bradley L

2013-04-01

Although molecular mechanisms promoting adherence of enterohemorrhagic Escherichia coli (EHEC) O157:H7 on epithelial cells are well characterized, regulatory mechanisms controlling biofilm formation are not fully understood. In this study, we demonstrate that biofilm formation in EHEC O157:H7 strain 86-24 is highly repressed compared to that in an isogenic hha mutant. The hha mutant produced large quantities of biofilm compared to the wild-type strain at 30°C and 37°C. Complementation of the hha mutant reduced the level of biofilm formation to that of the wild-type strain, indicating that Hha is a negative regulator of biofilm production. While swimming motility and expression of the flagellar gene fliC were significantly reduced, the expression of csgA (encoding curlin of curli fimbriae) and the ability to bind Congo red were significantly enhanced. The expression of both fliC and csgA and the phenotypes of motility and curli production affected by these two genes, respectively, were restored to wild-type levels in the complemented hha mutant. The csgA deletion abolished biofilm formation in the hha mutant and wild-type strain, and csgA complementation restored biofilm formation to these strains, indicating the importance of csgA and curli in biofilm formation. The regulatory effects of Hha on flagellar and curli gene expression appear to occur via the induction and repression of FlhDC and CsgD, as demonstrated by reduced flhD and increased csgD transcription in the hha mutant, respectively. In gel shift assays Hha interacted with flhDC and csgD promoters. In conclusion, Hha regulates biofilm formation in EHEC O157:H7 by differential regulation of FlhDC and CsgD, the global regulators of motility and curli production, respectively.
Therapeutic supermolecular micelles of vitamin E succinate-grafted ε-polylysine as potential carriers for curcumin: Enhancing tumour penetration and improving therapeutic effect on glioma.

PubMed

Xu, He-Lin; Fan, Zi-Liang; ZhuGe, De-Li; Shen, Bi-Xin; Jin, Bing-Hui; Xiao, Jian; Lu, Cui-Tao; Zhao, Ying-Zheng

2017-10-01

Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (D h ) of ca.20nm, and Zeta potential of 19.6mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma. The poorly water-soluble curcumin was effectively encapsulated in VES-g-PLL micelles with the drug loading amount and entrapment efficiency reaching 4.32% and 82.27%, respectively. In a physiologic medium, curcumin-loaded VES-g-PLL micelles (Cur-Micelles) not only remained stable without obvious drug leakage but also sustained the release of its encapsulated curcumin for a long time. Because of the ultra-small size and positively-charged surface, Cur-Micelles penetrated the deeper tumour zone than free curcumin, resulting in a significant inhibition of tumour spheroids growth. Moreover, in vivo strong antitumor effect of Cur-Micelles was also exhibited at assistance of ultrasound-targeted microbubble destruction and the real-time MRI imaging demonstrated a nearly complete suppression of glioma after 28days of treatment. TUNEL staining showed that the therapeutic mechanism of Cur-Micelles was relevant to the apoptosis of tumour cells. Finally, in vivo nontoxicity of Cur-Micelles against normal organs including heart, liver, spleen, lung and kidney tissues was also demonstrated by the HE staining. In conclusion, VES-g-PLL micelles may serve as a potential carrier for curcumin to enhance tumour penetration and improve therapeutic effect on glioma. Copyright © 2017 Elsevier B.V. All rights reserved.
A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate-Postgraduate-Faculty Triads.

PubMed

Aikens, Melissa L; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T; Dolan, Erin L

2016-01-01

Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as "postgraduates") and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the undergraduate's research. Using a social capital theory framework, we hypothesized that different triad structures provide undergraduates with varying resources (e.g., information, advice, psychosocial support) from the postgraduates and/or faculty, which would affect the undergraduates' research outcomes. To test this, we collected data from a national sample of undergraduate life science researchers about their mentoring triad structure and a range of outcomes associated with research experiences, such as perceived gains in their abilities to think and work like scientists, science identity, and intentions to enroll in a PhD program. Undergraduates mentored by postgraduates alone reported positive outcomes, indicating that postgraduates can be effective mentors. However, undergraduates who interacted directly with faculty realized greater outcomes, suggesting that faculty interaction is important for undergraduates to realize the full benefits of research. The "closed triad," in which undergraduates, postgraduates, and faculty all interact directly, appeared to be uniquely beneficial; these undergraduates reported the highest gains in thinking and working like a scientist. © 2016 M. L. Aikens et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
The impacts and "best practices" of undergraduate - graduate student mentoring relationships in undergraduate research experiences

NASA Astrophysics Data System (ADS)

Campanile, Megan Faurot

With the growth of undergraduate research in the U.S., over the past two decades, faculty are more often assigning graduate students to mentor undergraduate students than providing the one-on-one mentoring themselves. A critical gap that exists in the literature is how undergraduate -- graduate student mentoring relationships in undergraduate research influences both students' academic and career paths. The research questions that framed this study were: (1) What, if any, changes occur in the academic and career paths of undergraduate and graduate students who participate in undergraduate research experiences? and (2) Are there variables that constitute "best practices" in the mentoring relationships in undergraduate research experiences and, if so, what are they? The study context was the National Science Foundation Research Experiences for Undergraduates program at Illinois Institute of Technology and the 113 undergraduate researchers and 31 graduate student mentors who participated from 2006 -- 2014. Surveys and interviews were administered to collect pre- and post-program data and follow-up data during the 2014 -- 2015 academic year. Descriptive statistics, content analysis method, and constant comparative method were used to analyze the data. Key findings on the undergraduate researchers were their actual earned graduate degree types (Ph.D. 20%, M.D. 20%, M.S. 48%, other 12%) and fields (STEM 57%, medical 35%, other 8%) and the careers they were pursuing or working in. All the graduate student mentors were pursuing or working in the STEM fields (academia 50%, industry 40%, government 10%). More than 75% of both the undergraduate and graduate students reported that their mentoring relationships had a somewhat to extremely influential impact on their academic and career paths. A set of "best practices" of mentoring were developed for both the undergraduate and graduate students and focused on the mentoring experiences related to learning and teaching about research; relationship dynamics and roles; and, planning, practicing, and preparing for the future. Future studies recommended include additional longitudinal studies and comparative studies of programs with and without mentor training. Ultimately, by improving the mentoring relationships in undergraduate research it has the potential to improve both undergraduate and graduate education and produce a more highly qualified U.S. STEM workforce. oth undergraduate and graduate education and produce a more highly qualified U.S. STEM workforce.
Undergraduate research experiences support science career decisions and active learning.

PubMed

Lopatto, David

2007-01-01

The present study examined the reliability of student evaluations of summer undergraduate research experiences using the SURE (Survey of Undergraduate Research Experiences) and a follow-up survey disseminated 9 mo later. The survey further examines the hypothesis that undergraduate research enhances the educational experience of science undergraduates, attracts and retains talented students to careers in science, and acts as a pathway for minority students into science careers. Undergraduates participated in an online survey on the benefits of undergraduate research experiences. Participants indicated gains on 20 potential benefits and reported on career plans. Most of the participants began or continued to plan for postgraduate education in the sciences. A small group of students who discontinued their plans for postgraduate science education reported significantly lower gains than continuing students. Women and men reported similar levels of benefits and similar patterns of career plans. Undergraduate researchers from underrepresented groups reported higher learning gains than comparison students. The results replicated previously reported data from this survey. The follow-up survey indicated that students reported gains in independence, intrinsic motivation to learn, and active participation in courses taken after the summer undergraduate research experience.
Field Research in the Teaching of Undergraduate Soil Science

NASA Astrophysics Data System (ADS)

Brevik, Eric C.; Senturklu, Songul; Landblom, Douglas

2015-04-01

Several studies have demonstrated that undergraduate students benefit from research experiences. Benefits of undergraduate research include 1) personal and intellectual development, 2) more and closer contact with faculty, 3) the use of active learning techniques, 4) creation of high expectations, 5) development of creative and problem-solving skills, 6) greater independence and intrinsic motivation to learn, and 7) exposure to practical skills. The scientific discipline also benefits, as studies have shown that undergraduates who engage in research experiences are more likely to remain science majors and finish their degree program (Lopatto, 2007). Research experiences come as close as possible to allowing undergraduates to experience what it is like to be an academic or research member of their profession working to advance their discipline. Soils form in the field, therefore, field experiences are very important in developing a complete and holistic understanding of soil science. Combining undergraduate research with field experiences can provide extremely beneficial outcomes to the undergraduate student, including increased understanding of and appreciation for detailed descriptions and data analysis as well as an enhanced ability to see how various parts of their undergraduate education come together to understand a complex problem. The experiences of the authors in working with undergraduate students on field-based research projects will be discussed, along with examples of some of the undergraduate research projects that have been undertaken. In addition, student impressions of their research experiences will be presented. Reference Lopatto, D. 2007. Undergraduate research experiences support science career decisions and active learning. CBE -- Life Sciences Education 6:297-306.
[Glimpsing undergraduate research from the view of the advisors of Nursing scholarships].

PubMed

Erdmann, Alacoque Lorenzini; Leite, Joséte Luzia; Nascimento, Keyla Cristiane do; Lanzoni, Gabriela Marcellino de Melo

2011-01-01

This research aimed at understanding the meaning of undergraduate research for supervisors of Nursing scholarship students in a university in the South of Brazil. The methodological reference used was the Grounded Theory, by the means of interviews with seven undergraduate research scholarship advisors forming two sample groups. The phenomenon "glimpsing undergraduate research activities of research groups coordinated by nursing advisors, the basis of competency formation in research of the scholarships" emerged form the interrelation of six categories. To be a advisor and researcher of human resources in research form undergraduation requires pedagogical, instrumental, and managerial competencies associated to research policies of nursing and health.
Undergraduate Research Experience in Ocean/Marine Science (URE-OMS) with African Student Component

DTIC Science & Technology

2011-01-01

The Undergraduate Research Experience in Ocean/Marine Science program supports active participation by underrepresented undergraduate students in remote sensing and Ocean/Marine Science research training activities. The program is based on a model for undergraduate research programs supported by the National Science Foundation . The
Undergraduate Research in the Human Sciences: Three Models

ERIC Educational Resources Information Center

Collins, Nina; Mitstifer, Dorothy I.; Nelson Goff, Briana S.; Hymon-Parker, Shirley

2009-01-01

Undergraduate research in the sciences has been shown by numerous studies to enhance the educational experience. The Undergraduate Research Community (URC) founded in 2001 supports several initiatives that promote research in human sciences/family and consumer sciences including an online peer-reviewed journal specifically for undergraduate work,…
Engaging Undergraduates in Science Research: Not Just about Faculty Willingness

ERIC Educational Resources Information Center

Eagan, M. Kevin, Jr.; Sharkness, Jessica; Hurtado, Sylvia; Mosqueda, Cynthia M.; Chang, Mitchell J.

2011-01-01

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty…
Web-Based Surveys Facilitate Undergraduate Research and Knowledge

ERIC Educational Resources Information Center

Grimes, Paul, Ed.; Steele, Scott R.

2008-01-01

The author presents Web-based surveying as a valuable tool for achieving quality undergraduate research in upper-level economics courses. Web-based surveys can be employed in efforts to integrate undergraduate research into the curriculum without overburdening students or faculty. The author discusses the value of undergraduate research, notes…
Adversarial Geospatial Abduction Problems

DTIC Science & Technology

2011-01-01

which is new , shows that #GCD is #P-complete and, moreover, that there is no fully-polynomial random approximation scheme for #GCD unless NP equals the...use L∗ to form a new set of constraints to find a δ-core optimal explanation. We now present these δ-core constraints. Notice that the cardinality...EXBrf (∅, efd), flag1 = true, i = 2 (4) While flag1 (a) new val = cur val + inci (b) If new val > (1 + |L|2 ) · cur val then i. If EXBrf (B ∪ {pi

What Knowledge of Responsible Conduct of Research Do Undergraduates Bring to Their Undergraduate Research Experiences?

ERIC Educational Resources Information Center

Mabrouk, Patricia Ann

2016-01-01

Over a three-year period, chemistry and engineering students participating in six Research Experience for Undergraduates (REU) programs were surveyed before and after participating in a research ethics training workshop. The goal was to learn what undergraduate students already knew about key concepts in research ethics at the start of their…
An Investigation into Mentoring Practices of Faculty Who Mentor Undergraduate Researchers at a Hispanic Serving Institution

ERIC Educational Resources Information Center

Estepp, Christopher M.; Velasco, Joseph G.; Culbertson, Avery L.; Conner, Nathan W.

2017-01-01

Research has shown the benefits of undergraduate research; however, few studies have examined mentors of undergraduate researchers. The purpose of this study was to investigate the practices of mentors who have successfully mentored Hispanic undergraduate researchers. Findings from this study suggested that mentors should focus on interacting with…
Intellectual Growth for Undergraduate Students: Evaluation Results from an Undergraduate Research Conference

ERIC Educational Resources Information Center

Potter, Sharyn J.; Abrams, Eleanor; Townson, Lisa; Wake, Cameron; Williams, Julie E.

2010-01-01

We describe the development and evaluation of the university-wide, weeklong undergraduate research conference at the University of New Hampshire. Despite increases nationally in the number of undergraduate research conferences (URC), there has been little research examining the social and educational impact of these events on student presenters.…
A Social Capital Perspective on the Mentoring of Undergraduate Life Science Researchers: An Empirical Study of Undergraduate-Postgraduate-Faculty Triads

ERIC Educational Resources Information Center

Aikens, Melissa L.; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Eby, Lillian T.; Dolan, Erin L.

2016-01-01

Undergraduate researchers at research universities are often mentored by graduate students or postdoctoral researchers (referred to collectively as "postgraduates") and faculty, creating a mentoring triad structure. Triads differ based on whether the undergraduate, postgraduate, and faculty member interact with one another about the…
Course-based undergraduate research experiences in molecular biosciences-patterns, trends, and faculty support.

PubMed

Wang, Jack T H

2017-08-15

Inquiry-driven learning, research internships and course-based undergraduate research experiences all represent mechanisms through which educators can engage undergraduate students in scientific research. In life sciences education, the benefits of undergraduate research have been thoroughly evaluated, but limitations in infrastructure and training can prevent widespread uptake of these practices. It is not clear how faculty members can integrate complex laboratory techniques and equipment into their unique context, while finding the time and resources to implement undergraduate research according to best practice guidelines. This review will go through the trends and patterns in inquiry-based undergraduate life science projects with particular emphasis on molecular biosciences-the research-aligned disciplines of biochemistry, molecular cell biology, microbiology, and genomics and bioinformatics. This will provide instructors with an overview of the model organisms, laboratory techniques and research questions that are adaptable for semester-long projects, and serve as starting guidelines for course-based undergraduate research. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
An IDeA for enhancing undergraduate research at rural primarily undergraduate institutions.

PubMed

Sens, Donald A; Cisek, Karen L; Conway, Pat; Doze, Van A

2017-09-01

This study documents the efforts of the North Dakota (ND) IDeA Networks of Biomedical Research Excellence (INBRE) program to assist in the development of undergraduate research programs at four state-supported primarily undergraduate institutions (PUIs) in ND. The study was initiated in the 2004-2005 academic year and continues to the present. The study shows that gaining initial institutional support for undergraduate research was assisted by providing salary support for faculty involved in undergraduate research. Once research was ongoing, each institution evolved their own unique plan for the use of support from the ND INBRE. Undergraduate student researchers have prepared, presented, and defended their research results on 188 unique posters since initiation of the program, with many posters being presented at more than one meeting. PUI faculty have authored 35 peer-reviewed manuscripts. Evaluation has shown that over 95% of the undergraduate students performing research matriculated with their bachelor's degree. Career choices of 77.2% of these graduates was determined, and 37% pursued a career in the health professions. Of the students not pursuing a post-baccalaureate degree, 81.2% chose careers directly linked to science. The study reinforces the concept that undergraduate research can be performed directly on the PUI campus and be of value in preparing the next generation of health professionals in research, service, and teaching. Copyright © 2017 the American Physiological Society.
Imprinted-like biopolymeric micelles as efficient nanovehicles for curcumin delivery.

PubMed

Zhang, Lili; Qi, Zeyou; Huang, Qiyu; Zeng, Ke; Sun, Xiaoyi; Li, Juan; Liu, You-Nian

2014-11-01

To enhance the solubility and improve the bioavailability of hydrophobic curcumin, a new kind of imprinted-like biopolymeric micelles (IBMs) was designed. The IBMs were prepared via co-assembly of gelatin-dextran conjugates with hydrophilic tea polyphenol, then crosslinking the assembled micelles and finally removing the template tea polyphenol by dialysis. The obtained IBMs show selective binding for polyphenol analogous drugs over other drugs. Furthermore, curcumin can be effectively encapsulated into the IBMs with 5×10(4)-fold enhancement of aqueous solubility. We observed the sustained drug release behavior from the curcumin-loaded IBMs (CUR@IBMs) in typical biological buffers. In addition, we found the cell uptake of CUR@IBMs is much higher than that of free curcumin. The cell cytotoxicity results illustrated that CUR@IBMs can improve the growth inhibition of HeLa cells compared with free curcumin, while the blank IBMs have little cytotoxicity. The in vivo animal study demonstrated that the IBMs could significantly improve the oral bioavailability of curcumin. Copyright © 2014 Elsevier B.V. All rights reserved.
Curcumin-carrying nanoparticles prevent ischemia-reperfusion injury in human renal cells.

PubMed

Xu, Yong; Hu, Ning; Jiang, Wei; Yuan, Hong-Fang; Zheng, Dong-Hui

2016-12-27

Renal ischemia-reperfusion injury (IRI) is a major complication in clinical practice. However, despite its frequency, effective preventive/treatment strategies for this condition are scarce. Curcumin possesses antioxidant properties and is a promising potential protective agent against renal IRI, but its poor water solubility restricts its application. In this study, we constructed curcumin-carrying distearoylphosphatidylethanolamine-polyethylene glycol nanoparticles (Cur-NPs), and their effect on HK-2 cells exposed to IRI was examined in vitro. Curcumin encapsulated in NPs demonstrated improved water solubility and slowed release. Compared with the IRI and Curcumin groups, Cur-NP groups displayed significantly improved cell viability, downregulated protein expression levels of caspase-3 and Bax, upregulated expression of Bcl-2 protein, increased antioxidant superoxide dismutase level, and reduced apoptotic rate, reactive oxygen species level, and malondialdehyde content. Results clearly showed that Cur-NPs demonstrated good water solubility and slow release, as well as exerted protective effects against oxidative stress in cultured HK-2 cells exposed to IRI.
Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

PubMed

Li, Jinglei; Lee, Il Woo; Shin, Gye Hwa; Chen, Xiguang; Park, Hyun Jin

2015-08-01

Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route. Copyright © 2015 Elsevier B.V. All rights reserved.
Ferulic acid destabilizes preformed {beta}-amyloid fibrils in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito

2005-10-21

Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA{beta} formation from A{beta} and destabilizes preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependentlymore » inhibited fA{beta} formation from amyloid {beta}-peptide, as well as their extension. Moreover, it destabilized preformed fA{beta}s. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.« less
Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier.

PubMed

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma.
Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel.

PubMed

Chen, Daquan; Yu, Hongyun; Mu, Hongjie; Wei, Junhua; Song, Zhenkun; Shi, Hong; Liang, Rongcai; Sun, Kaoxiang; Liu, Wanhui

2013-04-15

In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.
A Tiered Mentoring Model of Exposing and Engaging Students with Research Throughout the Undergraduate Curriculum

NASA Astrophysics Data System (ADS)

Guerard, J.; Hayes, S. M.

2015-12-01

Incorporating research into undergraduate curricula has been linked to improved critical thinking, intellectual independence, and student retention, resulting in a graduating population more ready for the workforce or graduate school. We have designed a three-tier model of undergraduate chemistry courses that enable first-year students with no previous research experience to gain the skills needed to develop, fund and execute independent research projects by the close of their undergraduate studies. First-year students are provided with context through a broadly focused introductory class that exposes them to current faculty research activities, and also gives them direct experience with the research process through peer mentored research teams as they participate in faculty-directed projects. Mid-career undergraduate students receive exposure and support in two formats: illustrative examples from current faculty research are incorporated into lessons in core classes, and courses specially designed to foster research independence. This is done by providing content and process mentoring as students develop independent projects, write proposals, and build relationships with faculty and graduate students in research groups. Advanced undergraduates further develop their research independence performing student-designed projects with faculty collaboration that frequently result in tangible research products. Further, graduate students gain experience in mentoring though formal training, as well as through actively mentoring mid-career undergraduates. This novel, integrated approach enables faculty to directly incorporate their research into all levels of the undergraduate curriculum while fostering undergraduates in developing and executing independent projects and empowering mentoring relationships.
An Evaluation of Research Ethics in Undergraduate Health Science Research Methodology Programs at a South African University.

PubMed

Coetzee, Tanya; Hoffmann, Willem A; de Roubaix, Malcolm

2015-10-01

The amended research ethics policy at a South African University required the ethics review of undergraduate research projects, prompting the need to explore the content and teaching approach of research ethics education in health science undergraduate programs. Two qualitative data collection strategies were used: document analysis (syllabi and study guides) and semi-structured interviews with research methodology coordinators. Five main themes emerged: (a) timing of research ethics courses, (b) research ethics course content, (c) sub-optimal use of creative classroom activities to facilitate research ethics lectures, (d) understanding the need for undergraduate project research ethics review, and (e) research ethics capacity training for research methodology lecturers and undergraduate project supervisors. © The Author(s) 2015.
Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli.

PubMed

Pesavento, Christina; Becker, Gisela; Sommerfeldt, Nicole; Possling, Alexandra; Tschowri, Natalia; Mehlis, Anika; Hengge, Regine

2008-09-01

During the transition from post-exponential to stationary phase, Escherichia coli changes from the motile-planktonic to the adhesive-sedentary "lifestyle." We demonstrate this transition to be controlled by mutual inhibition of the FlhDC/motility and sigma(S)/adhesion control cascades at two distinct hierarchical levels. At the top level, motility gene expression and the general stress response are inversely coordinated by sigma(70)/sigma(FliA)/sigma(S) competition for core RNA polymerase and the FlhDC-controlled FliZ protein acting as a sigma(S) inhibitor. At a lower level, the signaling molecule bis-(3'-5')-cyclic-diguanosine monophosphate (c-di-GMP) reduces flagellar activity and stimulates transcription of csgD, which encodes an essential activator of adhesive curli fimbriae expression. This c-di-GMP is antagonistically controlled by sigma(S)-regulated GGDEF proteins (mainly YegE) and YhjH, an EAL protein and c-di-GMP phosphodiesterase under FlhDC/FliA control. The switch from motility-based foraging to the general stress response and curli expression requires sigma(S)-modulated down-regulation of expression of the flagellar regulatory cascade as well as proteolysis of the flagellar master regulator FlhDC. Control of YhjH by FlhDC and of YegE by sigma(S) produces a fine-tuned checkpoint system that "unlocks" curli expression only after down-regulation of flagellar gene expression. In summary, these data reveal the logic and sequence of molecular events underlying the motile-to-adhesive "lifestyle" switch in E. coli.
Factors affecting the number and type of student research products for chemistry and physics students at primarily undergraduate institutions: A case study.

PubMed

Mellis, Birgit; Soto, Patricia; Bruce, Chrystal D; Lacueva, Graciela; Wilson, Anne M; Jayasekare, Rasitha

2018-01-01

For undergraduate students, involvement in authentic research represents scholarship that is consistent with disciplinary quality standards and provides an integrative learning experience. In conjunction with performing research, the communication of the results via presentations or publications is a measure of the level of scientific engagement. The empirical study presented here uses generalized linear mixed models with hierarchical bootstrapping to examine the factors that impact the means of dissemination of undergraduate research results. Focusing on the research experiences in physics and chemistry of undergraduates at four Primarily Undergraduate Institutions (PUIs) from 2004-2013, statistical analysis indicates that the gender of the student does not impact the number and type of research products. However, in chemistry, the rank of the faculty advisor and the venue of the presentation do impact the number of research products by undergraduate student, whereas in physics, gender match between student and advisor has an effect on the number of undergraduate research products. This study provides a baseline for future studies of discipline-based bibliometrics and factors that affect the number of research products of undergraduate students.
Factors affecting the number and type of student research products for chemistry and physics students at primarily undergraduate institutions: A case study

PubMed Central

Soto, Patricia; Bruce, Chrystal D.; Lacueva, Graciela; Wilson, Anne M.; Jayasekare, Rasitha

2018-01-01

For undergraduate students, involvement in authentic research represents scholarship that is consistent with disciplinary quality standards and provides an integrative learning experience. In conjunction with performing research, the communication of the results via presentations or publications is a measure of the level of scientific engagement. The empirical study presented here uses generalized linear mixed models with hierarchical bootstrapping to examine the factors that impact the means of dissemination of undergraduate research results. Focusing on the research experiences in physics and chemistry of undergraduates at four Primarily Undergraduate Institutions (PUIs) from 2004–2013, statistical analysis indicates that the gender of the student does not impact the number and type of research products. However, in chemistry, the rank of the faculty advisor and the venue of the presentation do impact the number of research products by undergraduate student, whereas in physics, gender match between student and advisor has an effect on the number of undergraduate research products. This study provides a baseline for future studies of discipline-based bibliometrics and factors that affect the number of research products of undergraduate students. PMID:29698502
Realizing Student, Faculty, and Institutional Outcomes at Scale: Institutionalizing Undergraduate Research, Scholarship, and Creative Activity within Systems and Consortia

ERIC Educational Resources Information Center

Malachowski, Mitchell; Osborn, Jeffrey M.; Karukstis, Kerry K.; Ambos, Elizabeth L.

2015-01-01

This chapter reviews the evidence for the effectiveness of undergraduate research as a student, faculty, and institutional success pathway, and provides the context for the Council on Undergraduate Research's support for developing and enhancing undergraduate research in systems and consortia. The chapter also provides brief introductions to each…
Toward a Conceptual Framework for Measuring the Effectiveness of Course-Based Undergraduate Research Experiences in Undergraduate Biology

ERIC Educational Resources Information Center

Brownell, Sara E.; Kloser, Matthew J.

2015-01-01

Recent calls for reform have advocated for extensive changes to undergraduate science lab experiences, namely providing more authentic research experiences for students. Course-based Undergraduate Research Experiences (CUREs) have attempted to eschew the limitations of traditional "cookbook" laboratory exercises and have received…
Preliminary Study of Heat Transfer Correlation Development and Pressure Loss Behavior in Curved High Aspect Ratio Coolant Channels

DTIC Science & Technology

2008-12-01

coefficient over that which would be present in a straight channel (Seban and McLaughlin, 1963; McCormack, Welker, Kelleher, 1969; Sturgis and Mudawar , 1999...11. Also Eq. 11 will be applied to each angular location and downstream locations (i.e. mid-channel and exit locations). Sturgis and Mudawar ...Table 1. Published Curvature Terms Author Curvature term, φcur Comments Ito (1959) 1. 05.Re c cur d D Limited to Re(D/dc) 2 >6 Sturgis and Mudawar

Collaboration and Community Building in Summer Undergraduate Research Programs in the School of Earth Sciences at Stanford University

NASA Astrophysics Data System (ADS)

Nevle, R. J.; Watson Nelson, T.; Harris, J. M.; Klemperer, S. L.

2012-12-01

In 2012, the School of Earth Sciences (SES) at Stanford University sponsored two summer undergraduate research programs. Here we describe these programs and efforts to build a cohesive research cohort among the programs' diverse participants. The two programs, the Stanford School of Earth Sciences Undergraduate Research (SESUR) Program and Stanford School of Earth Sciences Summer Undergraduate Research in Geoscience and Engineering (SURGE) Program, serve different undergraduate populations and have somewhat different objectives, but both provide students with opportunities to work on strongly mentored yet individualized research projects. In addition to research, enrichment activities co-sponsored by both programs support the development of community within the combined SES summer undergraduate research cohort. Over the course of 6 to 9 months, the SESUR Program engages Stanford undergraduates, primarily rising sophomores and juniors, with opportunities to deeply explore Earth sciences research while learning about diverse areas of inquiry within SES. Now in its eleventh year, the SESUR experience incorporates the breadth of the scientific endeavor: finding an advisor, proposal writing, obtaining funding, conducting research, and presenting results. Goals of the SESUR program include (1) providing a challenging and rewarding research experience for undergraduates who wish to explore the Earth sciences; (2) fostering interdisciplinary study in the Earth sciences among the undergraduate population; and (3) encouraging students to major or minor in the Earth sciences and/or to complete advanced undergraduate research in one of the departments or programs within SES. The SURGE Program, now in its second year, draws high performing students, primarily rising juniors and seniors, from 14 colleges and universities nationwide, including Stanford. Seventy percent of SURGE students are from racial/ethnic backgrounds underrepresented in STEM fields, and approximately one-third are the first in their families to attend college. For eight weeks, SURGE scholars conduct independent research with the guidance of faculty, research group mentors, and program assistants. The primary objectives of the SURGE program are to (1) provide undergraduates with a research experience in SES; (2) prepare undergraduates for the process of applying to graduate school; (3) introduce undergraduates to career opportunities in the geosciences and engineering; and (4) increase diversity in SES graduate programs. Independent research, network building, and intense mentoring culminate in a final oral and poster symposium. SESUR and SURGE scholars jointly participate in enrichment activities including faculty research seminars; career, graduate school, and software training workshops; GRE preparation classes; and geoscience-oriented field trips. Interaction among our students takes place through both research and enrichment activities, creating a critical mass of undergraduate scholars and promoting community development. Pre- and post-program surveys indicate that the overall goals of both programs are being achieved.
Early Undergraduate Research Experiences Lead to Similar Learning Gains for STEM and Non-STEM Undergraduates

ERIC Educational Resources Information Center

Stanford, Jennifer S.; Rocheleau, Suzanne E.; Smith, Kevin P. W.; Mohan, Jaya

2017-01-01

Undergraduate research is touted as a high-impact educational practice yielding important benefits such as increased retention and notable learning gains. Large-scale studies describing benefits of mentored research programs have focused primarily on outcomes for science, technology, engineering and mathematics (STEM) undergraduates. The Students…
Framing the Undergraduate Research Experience: Discovery Involvement in Retailing Undergraduate Education

ERIC Educational Resources Information Center

Sternquist, Brenda; Huddleston, Patricia; Fairhurst, Ann

2018-01-01

We provide an overview of ways to involve undergraduate business and retailing students in faculty research projects and discuss advantages of these student-faculty collaborations. We use Kolb's experiential learning cycle to provide a framework for creating an effective and engaging undergraduate research experience and use it to classify types…
Undergraduate Research Mentoring: Obstacles and Opportunities

ERIC Educational Resources Information Center

Johnson, W. Brad; Behling, Laura L.; Miller, Paul; Vandermaas-Peeler, Maureen

2015-01-01

Researchers and policy-makers in higher education increasingly espouse the view that undergraduate students should have the opportunity to learn about scholarship and research in the context of faculty-mentored research experiences. There is mounting consensus that mentored undergraduate research should be standard pedagogical practice in all…
Increasing Research Productivity in Undergraduate Research Experiences: Exploring Predictors of Collaborative Faculty–Student Publications

PubMed Central

Morales, Danielle X.; Grineski, Sara E.; Collins, Timothy W.

2017-01-01

Little attention has been paid to understanding faculty–student productivity via undergraduate research from the faculty member’s perspective. This study examines predictors of faculty–student publications resulting from mentored undergraduate research, including measures of faculty–student collaboration, faculty commitment to undergraduate students, and faculty characteristics. Generalized estimating equations were used to analyze data from 468 faculty members across 13 research-intensive institutions, collected by a cross-sectional survey in 2013/2014. Results show that biomedical faculty mentors were more productive in publishing collaboratively with undergraduate students when they worked with students for more than 1 year on average, enjoyed teaching students about research, had mentored Black students, had received more funding from the National Institutes of Health, had a higher H-index scores, and had more years of experience working in higher education. This study suggests that college administrators and research program directors should strive to create incentives for faculty members to collaborate with undergraduate students and promote faculty awareness that undergraduates can contribute to their research. PMID:28747352
Improving undergraduate biology education in a large research university.

PubMed Central

Bender, C; Ward, S; Wells, M A

1994-01-01

The campus-wide Undergraduate Biology Research Program (UBRP) at the University of Arizona improves undergraduate science education by expanding student opportunities for independent research in faculty laboratories. Within the supportive community of a research laboratory, underclassmen, nonscience majors, and those aspiring to scientific careers all learn to appreciate the process of science. The Program impacts more than the students, promoting departmental cooperation, interdisciplinary collaborations, and improvements in undergraduate science education throughout a Research I University. PMID:8018999
Comb-like amphiphilic copolymers bearing acetal-functionalized backbones with the ability of acid-triggered hydrophobic-to-hydrophilic transition as effective nanocarriers for intracellular release of curcumin.

PubMed

Zhao, Junqiang; Wang, Haiyang; Liu, Jinjian; Deng, Liandong; Liu, Jianfeng; Dong, Anjie; Zhang, Jianhua

2013-11-11

The pH-responsive micelles have enormous potential as nanosized drug carriers for cancer therapy due to their physicochemical changes in response to the tumor intracellular acidic microenvironment. Herein, a series of comb-like amphiphilic copolymers bearing acetal-functionalized backbone were developed based on poly[(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl) ethane methacrylate-co-poly(ethylene glycol) methyl ether methacrylate] [P(TTMA-co-mPEGMA)] as effective nanocarriers for intracellular curcumin (CUR) release. P(TTMA-co-mPEGMA) copolymers with different hydrophobic-hydrophilic ratios were prepared by one-step reversible addition fragmentation chain transfer (RAFT) copolymerization of TTMA and mPEGMA. Their molecular structures and chemical compositions were confirmed by (1)H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). P(TTMA-co-mPEGMA) copolymers could self-assemble into nanosized micelles in aqueous solution and displayed low critical micelle concentration (CMC). All P(TTMA-co-mPEGMA) micelles displayed excellent drug loading capacity, due to the strong π-π conjugate action and hydrophobic interaction between the PTTMA and CUR. Moreover, the hydrophobic PTTMA chain could be selectively hydrolyzed into a hydrophilic backbone in the mildly acidic environment, leading to significant swelling and final disassembly of the micelles. These morphological changes of P(TTMA-co-mPEGMA) micelles with time at pH 5.0 were determined by DLS and TEM. The in vitro CUR release from the micelles exhibited a pH-dependent behavior. The release rate of CUR was significantly accelerated at mildly acidic pH of 4.0 and 5.0 compared to that at pH 7.4. Toxicity test revealed that the P(TTMA-co-mPEGMA) copolymers exhibited low cytotoxicity, whereas the CUR-loaded micelles maintained high cytotoxicity for HepG-2 and EC-109 cells. The results indicated that the novel P(TTMA-co-mPEGMA) micelles with low CMC, small and tunable sizes, high drug loading, pH-responsive drug release behavior, and good biocompatibility may have potential as hydrophobic drug delivery nanocarriers for cancer therapy with intelligent delivery.
Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

PubMed Central

2012-01-01

Background Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities. Conclusion Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA. PMID:22448640
Emphasizing Research (Further) in Undergraduate Technical Communication Curricula: Involving Undergraduate Students with an Academic Journal's Publication and Management

ERIC Educational Resources Information Center

Ford, Julie Dyke; Newmark, Julianne

2011-01-01

This article presents follow-up information to a previous publication regarding ways to increase emphasis on research skills in undergraduate Technical Communication curricula. We detail the ways our undergraduate program highlights research by requiring majors to complete senior thesis projects that culminate in submission to an online…
JERHRE's New Web Pages.

PubMed

2006-06-01

JERHRE'S WEBSITE, www.csueastbay.edu/JERHRE/ has two new pages. One of those pages is devoted to curriculum that may be used to educate students, investigators and ethics committee members about issues in the ethics of human subjects research, and to evaluate their learning. It appears at www.csueastbay.edu/JERHRE/cur.html. The other is devoted to emailed letters from readers. Appropriate letters will be posted as soon as they are received by the editor. Letters from readers appear at www.csueastbay.edu/JERHRE/let.html.
What do medical students understand by research and research skills? Identifying research opportunities within undergraduate projects.

PubMed

Murdoch-Eaton, Deborah; Drewery, Sarah; Elton, Sarah; Emmerson, Catherine; Marshall, Michelle; Smith, John A; Stark, Patsy; Whittle, Sue

2010-01-01

Undergraduate research exposure leads to increased recruitment into academic medicine, enhanced employability and improved postgraduate research productivity. Uptake of undergraduate research opportunities is reported to be disappointing, and little is known about how students perceive research. To investigate opportunities for undergraduate participation in research, recognition of such opportunities, and associated skills development. A mixed method approach, incorporating student focus and study groups, and documentary analysis at five UK medical schools. Undergraduates recognised the benefits of acquiring research skills, but identified practical difficulties and disadvantages of participating. Analysis of 905 projects in four main research skill areas - (1) research methods; (2) information gathering; (3) critical analysis and review; (4) data processing - indicated 52% of projects provided opportunities for students to develop one or more skills, only 13% offered development in all areas. In 17%, project descriptions provided insufficient information to determine opportunities. Supplied with information from a representative sample of projects (n = 80), there was little consensus in identifying skills among students or between students and researchers. Consensus improved dramatically following guidance on how to identify skills. Undergraduates recognise the benefits of research experience but need a realistic understanding of the research process. Opportunities for research skill development may not be obvious. Undergraduates require training to recognise the skills required for research and enhanced transparency in potential project outcomes.
Engineered catalytic biofilms: Site-specific enzyme immobilization onto E. coli curli nanofibers.

PubMed

Botyanszki, Zsofia; Tay, Pei Kun R; Nguyen, Peter Q; Nussbaumer, Martin G; Joshi, Neel S

2015-10-01

Biocatalytic transformations generally rely on purified enzymes or whole cells to perform complex transformations that are used on industrial scale for chemical, drug, and biofuel synthesis, pesticide decontamination, and water purification. However, both of these systems have inherent disadvantages related to the costs associated with enzyme purification, the long-term stability of immobilized enzymes, catalyst recovery, and compatibility with harsh reaction conditions. We developed a novel strategy for producing rationally designed biocatalytic surfaces based on Biofilm Integrated Nanofiber Display (BIND), which exploits the curli system of E. coli to create a functional nanofiber network capable of covalent immobilization of enzymes. This approach is attractive because it is scalable, represents a modular strategy for site-specific enzyme immobilization, and has the potential to stabilize enzymes under denaturing environmental conditions. We site-specifically immobilized a recombinant α-amylase, fused to the SpyCatcher attachment domain, onto E. coli curli fibers displaying complementary SpyTag capture domains. We characterized the effectiveness of this immobilization technique on the biofilms and tested the stability of immobilized α-amylase in unfavorable conditions. This enzyme-modified biofilm maintained its activity when exposed to a wide range of pH and organic solvent conditions. In contrast to other biofilm-based catalysts, which rely on high cellular metabolism, the modified curli-based biofilm remained active even after cell death due to organic solvent exposure. This work lays the foundation for a new and versatile method of using the extracellular polymeric matrix of E. coli for creating novel biocatalytic surfaces. © 2015 Wiley Periodicals, Inc.
Development, optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis.

PubMed

Chauhan, Sheetal; Bansal, Monika; Khan, Gayasuddin; Yadav, Sarita K; Singh, Ashish K; Prakash, Pradyot; Mishra, Brahmeshwar

2018-07-01

Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis. Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis. The film was developed by using solvent casting technique and "Design of Experiments" approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior. Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days. The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis.
Cellulose as an Architectural Element in Spatially Structured Escherichia coli Biofilms

PubMed Central

Serra, Diego O.; Richter, Anja M.

2013-01-01

Morphological form in multicellular aggregates emerges from the interplay of genetic constitution and environmental signals. Bacterial macrocolony biofilms, which form intricate three-dimensional structures, such as large and often radially oriented ridges, concentric rings, and elaborate wrinkles, provide a unique opportunity to understand this interplay of “nature and nurture” in morphogenesis at the molecular level. Macrocolony morphology depends on self-produced extracellular matrix components. In Escherichia coli, these are stationary phase-induced amyloid curli fibers and cellulose. While the widely used “domesticated” E. coli K-12 laboratory strains are unable to generate cellulose, we could restore cellulose production and macrocolony morphology of E. coli K-12 strain W3110 by “repairing” a single chromosomal SNP in the bcs operon. Using scanning electron and fluorescence microscopy, cellulose filaments, sheets and nanocomposites with curli fibers were localized in situ at cellular resolution within the physiologically two-layered macrocolony biofilms of this “de-domesticated” strain. As an architectural element, cellulose confers cohesion and elasticity, i.e., tissue-like properties that—together with the cell-encasing curli fiber network and geometrical constraints in a growing colony—explain the formation of long and high ridges and elaborate wrinkles of wild-type macrocolonies. In contrast, a biofilm matrix consisting of the curli fiber network only is brittle and breaks into a pattern of concentric dome-shaped rings separated by deep crevices. These studies now set the stage for clarifying how regulatory networks and in particular c-di-GMP signaling operate in the three-dimensional space of highly structured and “tissue-like” bacterial biofilms. PMID:24097954
Cellulose as an architectural element in spatially structured Escherichia coli biofilms.

PubMed

Serra, Diego O; Richter, Anja M; Hengge, Regine

2013-12-01

Morphological form in multicellular aggregates emerges from the interplay of genetic constitution and environmental signals. Bacterial macrocolony biofilms, which form intricate three-dimensional structures, such as large and often radially oriented ridges, concentric rings, and elaborate wrinkles, provide a unique opportunity to understand this interplay of "nature and nurture" in morphogenesis at the molecular level. Macrocolony morphology depends on self-produced extracellular matrix components. In Escherichia coli, these are stationary phase-induced amyloid curli fibers and cellulose. While the widely used "domesticated" E. coli K-12 laboratory strains are unable to generate cellulose, we could restore cellulose production and macrocolony morphology of E. coli K-12 strain W3110 by "repairing" a single chromosomal SNP in the bcs operon. Using scanning electron and fluorescence microscopy, cellulose filaments, sheets and nanocomposites with curli fibers were localized in situ at cellular resolution within the physiologically two-layered macrocolony biofilms of this "de-domesticated" strain. As an architectural element, cellulose confers cohesion and elasticity, i.e., tissue-like properties that-together with the cell-encasing curli fiber network and geometrical constraints in a growing colony-explain the formation of long and high ridges and elaborate wrinkles of wild-type macrocolonies. In contrast, a biofilm matrix consisting of the curli fiber network only is brittle and breaks into a pattern of concentric dome-shaped rings separated by deep crevices. These studies now set the stage for clarifying how regulatory networks and in particular c-di-GMP signaling operate in the three-dimensional space of highly structured and "tissue-like" bacterial biofilms.
The Peer Assisted Teaching Model for Undergraduate Research at a HBCU

ERIC Educational Resources Information Center

Wu, Liyun; Lewis, Marilyn W.

2018-01-01

Despite wide application of research skills in higher education, undergraduate students reported research and computer anxiety, and low association between research and their professional goals. This study aims to assess whether peer-assisted mentoring programs would promote positive changes in undergraduates' attitudes toward research. Using a…
Evaluation of a Research Experiences for Undergraduates Program in ChE Indicates Benefit from a Collaborative Model

ERIC Educational Resources Information Center

Follmer, D. Jake; Gomez, Esther; Zappe, Sarah; Kumar, Manish

2017-01-01

This study examined how a collaborative research environment in a structured research experience impacts undergraduate student outcomes. Students demonstrated significant gains in research skills and provided positive appraisals of their collaborative experiences. Emphasis on collaboration among students in an undergraduate research program…
Lowering Barriers to Undergraduate Research through Collaboration with Local Craft Breweries

ERIC Educational Resources Information Center

McDermott, M. Luke

2016-01-01

Laboratory research experiences are highly impactful learning environments for undergraduate students. However, a surprising number of chemistry students do not research. These students often do not research because they lack the time, interest, opportunity, or awareness. Course-based undergraduate research experiences can reach out to these…
Race and Gender Differences in Undergraduate Research Mentoring Structures and Research Outcomes

ERIC Educational Resources Information Center

Aikens, Melissa L.; Robertson, Melissa M.; Sadselia, Sona; Watkins, Keiana; Evans, Mara; Runyon, Christopher R.; Eby, Lillian T.; Dolan, Erin L.

2017-01-01

Participating in undergraduate research with mentorship from faculty may be particularly important for ensuring the persistence of women and minority students in science. Yet many life science undergraduates at research universities are mentored by graduate or postdoctoral researchers (i.e., postgraduates). We surveyed a national sample of…
Lessons Learned: The Evolution of an Undergraduate Research Program

ERIC Educational Resources Information Center

Smith, Gregory; Laker, Lauren; Tesch, Debbie

2013-01-01

Undergraduate research programs are commonplace at many universities. However, little research has been conducted to evaluate their ongoing and long-term effectiveness from the standpoint of the undergraduate student researcher. In an effort to gain perspective from the student researcher, including their thoughts on such a program, a survey was…

A Workbook for Scaffolding Mentored Undergraduate Research Experiences in the Social and Behavioral Sciences

ERIC Educational Resources Information Center

Colbert-White, Erin; Simpson, Elizabeth

2017-01-01

Research mentors strive to ensure that undergraduates gain research skills and develop professionally during mentored research experiences in the sciences. We created the SURE (Specialized Undergraduate Research Experience) Workbook, a freely-available, interactive guide to scaffold student learning during this process. The Workbook: (1)…
The Role of High School Research Experiences in Shaping Students' Research Self-Efficacy and Preparation for Undergraduate Research Participation

ERIC Educational Resources Information Center

Swan, Amy K.; Inkelas, Karen Kurotsuchi; Jones, Jill N.; Pretlow, Joshua; Keller, Tierney F.

2018-01-01

The effects of undergraduate research participation are well documented, but less is known about students' pathways into undergraduate research participation. This mixed-methods study explored the role of an International Baccalaureate research project in students' development of research self-efficacy in high school, and how this development…
Alive and aware: Undergraduate research as a mechanism for program vitalization

NASA Astrophysics Data System (ADS)

Rohs, C.

2013-12-01

Undergraduate research is a vital component of many geoscience programs across the United States. It is especially critical at those institutions that do not have graduate students or graduate programs in the geosciences. This paper presents findings associated with undergraduate research in four specific areas: The success of students that pursue undergraduate research both in the workforce and in graduate studies; the connections that are generated through undergraduate research and publication; the application of undergraduate research data and materials in the classroom; and the development of lasting connections between faculty and students to construct a strong alumni base to support the corresponding programs. Students that complete undergraduate research have the opportunity to develop research proposals, construct budgets, become familiar with equipment or software, write and defend their results. This skill set translates directly to graduate studies; however, it is also extremely valuable for self-marketing when seeking employment as a geoscientist. When transitioning from higher education into the workforce, a network of professional connections facilitates and expedites the process. When completing undergraduate research, students have a direct link to the faculty member that they are working with, and potentially, the network of that faculty member. Even more important, the student begins to build their own professional network as they present their findings and receive feedback on their research. Another area that benefits from undergraduate research is the classroom. A cyclical model is developed where new data and information are brought into the classroom by the faculty member, current students see the impact of undergraduate research and have the desire to participate, and a few of those students elect to participate in a project of their own. It turns into a positive feedback loop that is beneficial for both the students and the faculty members. Finally, it is important to look at the long-range benefit of undergraduate research as an investment that pays off through alumni in the years to come. These alumni have the potential to become the pillars in support of the geoscience program. With their support, the program and associated department becomes strengthened and continues to develop in order to provide for the geoscience workforce needs of the future.
Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology.

PubMed

Guo, Fangyuan; Guo, Dingjia; Zhang, Wei; Yan, Qinying; Yang, Yan; Hong, Weiyong; Yang, Gensheng

2017-03-01

Biodegradable polymeric nanoparticles (NPs) have potential therapeutic applications; however, preparing NPs of a specific diameter and uniform size distribution is a challenge. In this work, we fabricated a microchannel system for the preparation of curcumin (Cur)-loaded NPs by the interfacial precipitation method, which rapidly and consistently generated stable NPs with a relatively smaller diameter, narrow size distribution, and higher drug-loading capacity and entrapment efficiency. Poly(ε-caprolactone)-poly(ethylene glycol)-poly (ε-caprolactone) triblock copolymers(PCEC) used as the carrier material was synthesized and characterized. Cur-loaded PCEC NPs had an average size of 167.2nm with a zeta potential of -29.23mV, and showed a loading capacity and drug entrapment efficiency of 15.28%±0.23% and 96.11%±0.13%, respectively. Meanwhile, the NPs demonstrated good biocompatibility and bioavailability, efficient cellular uptake, and long circulation time and a possible liver targeting effect in vivo. These results indicate that the Cur-loaded PCEC NPs can be used as drug carriers in controlled delivery systems and other biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.
A curly-tail modifier locus, mct1, on mouse chromosome 17

DOE Office of Scientific and Technical Information (OSTI.GOV)

Letts, V.A.; Schork, N.J.; Frankel, W.N.

1995-10-10

The major gene for neural tube defects, ct, in the curly-tail (CT) mouse strain was mapped previously to mouse chromosome 4 by combining linkage data from several backcrosses. The penetrance of the neural tube trait, already incomplete in the CT strain, was further reduced in several of these backcrosses, suggesting the existence of recessive modifiers or strain-specific susceptibility alleles. Here we describe the mapping of a curly-tail modifier locus, mct1, to chromosome 17 in moderate and low penetrance crosses of CT with BALB/cByJ and Mus spretus. No effect of mct1 was seen in a higher penetrance cross with the BXD-8/Tymore » strain, confirming that ct is the major gene in the model. Homozygosity at both ct and mct1 loci was sufficient to account for all of the affected individuals in the BALB/cByJ cross and most of the affected individuals in the M. spretus cross and was the preferred model overall. No evidence was found for epistatic interaction between ct and mct1. 30 refs., 2 figs., 3 tabs.« less
1H NMR-based metabolomic profiling for identification of metabolites in Capsicum annuum cv. mirasol infected by beet mild curly top virus (BMCTV).

PubMed

Villa-Ruano, Nemesio; Velásquez-Valle, Rodolfo; Zepeda-Vallejo, L Gerardo; Pérez-Hernández, Nury; Velázquez-Ponce, Manuel; Arcos-Adame, Victor M; Becerra-Martínez, Elvia

2018-04-01

Beet mild curly top virus (BMCTV) is associated with an outbreak of curly top in chili pepper, tomato and other Solanaceae species, which can cause severe crop losses. The aim of this work was to obtain the 1 H NMR metabolomic profiling of both healthy chili peppers (cv. mirasol) and infected chili peppers with BMCTV in order to find chemical markers associated to the infection process. Significant differences were found between the two groups, according to principal component analysis and orthogonal projections to latent structure discriminant analysis. Compared to the asymptomatic peppers, the symptomatic fruits had higher relative abundance of fructose, isoleucine, histidine, phenylalanine and tryptophan. Contrarily, the asymptomatic samples showed greater amounts of malonate and isobutyrate. These results suggest that in diseased chili peppers there are metabolic changes related to the viral acquisition of energy for replication and capsid assembly. This is the first study describing the chemical profiling of a polar extract obtained from Capsicum annuum infected by BMCTV under open field conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.
Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier

PubMed Central

Lv, Yongjiu; Li, Jingjing; Chen, Huali; Bai, Yan; Zhang, Liangke

2017-01-01

In this study, a glycyrrhetinic acid-functionalized mesoporous silica nanoparticle (MSN-GA) was prepared for active tumor targeting. MSN-GA exhibited satisfactory loading capacity for insoluble drugs, uniform size distribution, and specific tumor cell targeting. Glycyrrhetinic acid, a hepatocellular carcinoma-targeting group, was covalently decorated on the surface of MSN via an amido bond. The successful synthesis of MSN-GA was validated by the results of Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and zeta potential measurement. TEM images revealed the spherical morphology and uniform size distribution of the naked MSN and MSN-GA. Curcumin (CUR), an insoluble model drug, was loaded into MSN-GA (denoted as MSN-GA-CUR) with a high-loading capacity (8.78%±1.24%). The results of the in vitro cellular experiment demonstrated that MSN-GA-CUR significantly enhanced cytotoxicity and cellular uptake toward hepatocellular carcinoma (HepG2) cells via a specific GA receptor-mediated endocytosis mechanism. The results of this study provide a promising nanoplatform for the targeting of hepatocellular carcinoma. PMID:28652738
Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3.

PubMed

Ting, Stephen B; Wilanowski, Tomasz; Auden, Alana; Hall, Mark; Voss, Anne K; Thomas, Tim; Parekh, Vishwas; Cunningham, John M; Jane, Stephen M

2003-12-01

The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation studies that a mouse homolog of the Drosophila grainyhead (grh) gene, grainyhead-like-3 (Grhl3), is a compelling candidate for the gene underlying the curly tail phenotype. The NTDs in Grhl3-null mice are more severe than those in the curly tail strain, as the Grhl3 alleles in ct/ct mice are hypomorphic. Spina bifida in ct/ct mice is folate resistant, but its incidence can be markedly reduced by maternal inositol supplementation periconceptually. The NTDs in Grhl3-/- embryos are also folate resistant, but unlike those in ct/ct mice, they are resistant to inositol. These findings suggest that residual Grhl3 expression in ct/ct mice may be required for inositol rescue of folate-resistant NTDs.
Facile approach to synthesis the curly leaf-like Nano-sheets of g-C3N4 with enhanced photocatalytic ability

NASA Astrophysics Data System (ADS)

Zhao, Zhiren; Li, Kebin; Muhmood, Tahir; Xia, Mingzhu; Wang, Fengyun

2018-03-01

Exfoliation of porous g-C3N4 has been proved a very effective way to prepare g-C3N4 nanosheets (2D layered materials). Here, we present an environment-friendly, high-efficiency and easy scale-up preparation method of curly leaf-like g-C3N4 nanosheets (CL-CN) by liquid-phase exfoliation of honeycomb-like porous g-C3N4 (HP-CN). Two-dimensional curly nanosheets have induced excellent physicochemical properties, i.e. large surface area, high fluorescence quantum efficiency, wide band gap and good water-dispersibility. The photocatalytic performance of CL-CN in degradation of RhB under visible light is much better than that of honeycomb-like porous g-C3N4 and bulk g-C3N4. The improved photocatalytic performance of CL-CN is well explained by the improved physicochemical properties and photocatalytic mechanism. In addition, CL-CN being a 2D layered material with excellent photoluminescence characteristic and non-toxic behavior can be widely applied in bio-medicine, bio-imaging and biosensors field.
A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

NASA Astrophysics Data System (ADS)

Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

2017-04-01

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.
Social Work Faculty and Undergraduate Research Mentorships

ERIC Educational Resources Information Center

Horner, Pilar S.; Hughes, Anne K.; Vélez Ortiz, Daniel

2016-01-01

Social work faculty scholars lead the field as generators of knowledge that integrates investigative studies with practical social welfare outcomes. As such, the faculty potentially offers undergraduate researchers a different way of envisioning research that extends beyond traditional undergraduate research models. To date, however, no research…
Implementation of a Collaborative Series of Classroom-Based Undergraduate Research Experiences Spanning Chemical Biology, Biochemistry, and Neurobiology

ERIC Educational Resources Information Center

Kowalski, Jennifer R.; Hoops, Geoffrey C.; Johnson, R. Jeremy

2016-01-01

Classroom undergraduate research experiences (CUREs) provide students access to the measurable benefits of undergraduate research experiences (UREs). Herein, we describe the implementation and assessment of a novel model for cohesive CUREs focused on central research themes involving faculty research collaboration across departments. Specifically,…
Undergraduate Research Engagement at Major US Research Universities. Research & Occasional Paper Series: CSHE.14.13

ERIC Educational Resources Information Center

Douglass, John Aubrey; Zhao, Chun-Mei

2013-01-01

Bolstered by the recommendations of the 1998 Boyer Report, US federal agencies have put significant resources into promoting opportunities for undergraduates to engage in research. American universities and colleges have been creating support programs and curricular opportunities intended to create a "culture of undergraduate research."…
From Inquiry-Based Learning to Student Research in an Undergraduate Mathematics Program

ERIC Educational Resources Information Center

Das, Kumer

2013-01-01

As an extension to various sponsored summer undergraduate research programs, academic year research for undergraduate students is becoming popular. Mathematics faculty around the country are getting involved with this type of research and administrators are encouraging this effort. Since 2007, we have been conducting academic year research at…
Defining Quality in Undergraduate Education: Directions for Future Research Informed by a Literature Review

ERIC Educational Resources Information Center

Bowers, Alison W.; Ranganathan, Shyam; Simmons, Denise R.

2018-01-01

Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted…
Researching Undergraduate Social Science Research

ERIC Educational Resources Information Center

Rand, Jane

2016-01-01

The experience(s) of undergraduate research students in the social sciences is under-represented in the literature in comparison to the natural sciences or science, technology, engineering and maths (STEM). The strength of STEM undergraduate research learning environments is understood to be related to an apprenticeship-mode of learning supported…
Undergraduates and Research: Connectivity in the University

ERIC Educational Resources Information Center

Hordern, Jim

2013-01-01

Contemporary universities are engaged in multiple activities, which are often disconnected and subject to powerful external influences. Undergraduate research projects have been posited as a means of enhancing undergraduate education and improving the integration of research and teaching. However, engagement with the core research activity of the…
Preliminary Study of Heat Transfer Correlation Development and Pressure Loss Behavior in Curved High Aspect Ratio Coolant Channels (Preprint)

DTIC Science & Technology

2008-06-19

be present in a straight channel (Seban and McLaughlin, 1963; McCormack, Welker, Kelleher, 1969; Sturgis and Mudawar , 1999). However, it is unclear...and downstream locations (i.e. mid-channel and exit locations). Sturgis and Mudawar (1999) and Sturgis and Nathman (2008) provide lists of curvature...Terms Author Curvature term, φcur Comments Ito (1959) 1. 05.Re          c cur d D  Limited to Re(D/dc)2>6 Sturgis and Mudawar (1999) 1
Undergraduate Science Coursework: Teachers' Goal Statements and How Students Experience Research

ERIC Educational Resources Information Center

Van der Rijst, Roeland M.; Visser-Wijnveen, Gerda J.; Verloop, Nico; Van Driel, Jan H.

2013-01-01

Understanding the relation between teachers' goal statements and students' experiences about the position of research in undergraduate coursework can give use insight into ways to integrate research and teaching and foster undergraduate research. In this study, we examined to what extent teachers' goal statements agreed with students' experiences…
Engaging Undergraduates in Social Science Research: The Taking the Pulse of Saskatchewan Project

ERIC Educational Resources Information Center

Berdahl, Loleen

2014-01-01

Although student involvement in research and inquiry can advance undergraduate learning, there are limited opportunities for undergraduate students to be directly involved in social science research. Social science faculty members typically work outside of laboratory settings, with the limited research assistance work being completed by graduate…

Course-Based Undergraduate Research Experiences Can Make Scientific Research More Inclusive

ERIC Educational Resources Information Center

Bangera, Gita; Brownell, Sara E.

2014-01-01

Current approaches to improving diversity in scientific research focus on graduating more science, technology, engineering, and mathematics (STEM) majors, but graduation with a STEM undergraduate degree alone is not sufficient for entry into graduate school. Undergraduate independent research experiences are becoming more or less a prerequisite…
Undergraduate Research in the Dartmouth Economics Department

ERIC Educational Resources Information Center

Feyrer, James

2017-01-01

One of the key components to the undergraduate research enterprise at Dartmouth is the recognition that learning to do research requires both directed instruction and learning by doing. The economics faculty have tailored a fruitful undergraduate research program based on this philosophy, and this article describes these efforts while also…
Student and Faculty Outcomes of Undergraduate Science Research Projects by Geographically Dispersed Students

ERIC Educational Resources Information Center

Shaw, Lawton; Kennepohl, Dietmar

2013-01-01

Senior undergraduate research projects are important components of most undergraduate science degrees. The delivery of such projects in a distance education format is challenging. Athabasca University (AU) science project courses allow distance education students to complete research project courses by working with research supervisors in their…
Learning, Teaching and Scholarship: Fundamental Tensions of Undergraduate Research

ERIC Educational Resources Information Center

Laursen, Sandra; Seymour, Elaine; Hunter, Anne-Barrie

2012-01-01

Each year, thousands of undergraduates in the science, technology, engineering, and mathematics (STEM) fields conduct research in US university and college laboratories. Such undergraduate research (UR) experiences are common practice in US higher education, with nearly a century of history at research universities and liberal arts colleges.…
Undergraduate Students' Development of Social, Cultural, and Human Capital in a Networked Research Experience

ERIC Educational Resources Information Center

Thompson, Jennifer Jo; Conaway, Evan; Dolan, Erin L.

2016-01-01

Recent calls for reform in undergraduate biology education have emphasized integrating research experiences into the learning experiences of all undergraduates. Contemporary science research increasingly demands collaboration across disciplines and institutions to investigate complex research questions, providing new contexts and models for…
Explorations: A Research-Based Program Introducing Undergraduates to Diverse Biology Research Topics Taught by Grad Students and Postdocs

ERIC Educational Resources Information Center

Brownell, Sara E.; Khalfan, Waheeda; Bergmann, Dominique; Simoni, Robert

2013-01-01

Undergraduate biology majors are often overwhelmed by and underinformed about the diversity and complexity of biological research that is conducted on research-intensive campuses. We present a program that introduces undergraduates to the diversity and scope of biological research and also provides unique teaching opportunities for graduate…
Undergraduate Chemistry Education: A Workshop Summary

ERIC Educational Resources Information Center

Sawyer, Keegan; Alper, Joe

2014-01-01

"Undergraduate Chemistry Education" is the summary of a workshop convened in May 2013 by the Chemical Science Roundtable of the National Research Council to explore the current state of undergraduate chemistry education. Research and innovation in undergraduate chemistry education has been done for many years, and one goal of this…
Negotiating Peer Mentoring Roles in Undergraduate Research Lab Settings

ERIC Educational Resources Information Center

Packard, Becky W.; Marciano, Vincenza N.; Payne, Jessica M.; Bledzki, Leszek A.; Woodard, Craig T.

2014-01-01

Undergraduate research is viewed as an important catalyst for educational engagement and persistence, with an emphasis on the faculty mentoring relationship. Despite the common practice of having multi-tiered lab teams composed of newer undergraduates and more seasoned undergraduates serving as peer mentors, less is understood about the experience…
Why Work with Undergraduate Researchers? Differences in Research Advisors’ Motivations and Outcomes by Career Stage

PubMed Central

Hayward, Charles N.; Laursen, Sandra L.; Thiry, Heather

2017-01-01

Undergraduate research is often hailed as a solution to increasing the number and quality of science, technology, engineering, and mathematics graduates needed to fill the high-tech jobs of the future. Student benefits of research are well documented but the emerging literature on advisors’ perspectives is incomplete: only a few studies have included the graduate students and postdocs who often serve as research advisors, and not much is known about why research advisors choose to work with undergraduate researchers. We report the motivations for advising undergraduate researchers, and the related costs and benefits of doing so, from 30 interviews with research advisors at various career stages. Many advisors stated intrinsic motivations, but a small group of early-career advisors expressed only instrumental motivations. We explore what this means for how advisors work with student researchers, the benefits students may or may not gain from the experience, and the implications for training and retaining research advisors who can provide high-quality research experiences for undergraduate students. PMID:28213583
Undergraduate Research Experience in Ocean/Marine Science (URE-OMS)

DTIC Science & Technology

2003-09-30

The URE-Ocean/Marine Science program supports active research participation by undergraduate students in remote sensing and GIS. The program is based on a model for undergraduate research programs supported by the National Science Foundation . URE project features mentors, research projects, and professional development opportunities. It is the long-term goal
Undergraduate Student Teachers' Views and Experiences of a Compulsory Course in Research Methods

ERIC Educational Resources Information Center

Lombard, B. J. J.

2015-01-01

In comparison to attention given to research methods for education students at postgraduate level, the offering of research methods for education students at undergraduate level is less often considered. Yet, it is agreed that research methods for undergraduate level students is important for shaping student attitudes, learning and achievement in…
Research and Teaching: Development of Course-Based Undergraduate Research Experiences Using a Design-Based Approach

ERIC Educational Resources Information Center

Mordacq, John C.; Drane, Denise L.; Swarat, Su L.; Lo, Stanley M.

2017-01-01

In recent years, commissions and reports have called for laboratory courses that engage undergraduates in authentic research experiences. We present an iterative approach for developing course-based undergraduate research experiences (CUREs) that help students learn scientific inquiry skills and foster expert-like perceptions about biology. This…
A Combination Course and Lab-Based Approach to Teaching Research Skills to Undergraduates

ERIC Educational Resources Information Center

Danowitz, Amy M.; Brown, Ronald C.; Jones, Clinton D.; Diegelman-Parente, Amy; Taylor, Christopher E.

2016-01-01

Undergraduate research is an important capstone experience that provides students with the conceptual and technical aptitude for graduate or industrial research. However, this experience is often compressed into a single term in a course-based undergraduate research experience (CURE) or run by individual faculty members for select students on an…
"In Practice It Doesn't Always Work out Like That." Undergraduate Experiences in a Research Community of Practice

ERIC Educational Resources Information Center

John, Joanna; Creighton, John

2013-01-01

This paper examines the extent to which a structured undergraduate research intervention, UROP, permits undergraduate students early access to legitimate peripheral participation (LPP) in a research community of practice. Accounts of placement experiences suggest that UROP affords rich possibilities for engagement with research practice.…
Undergraduate Research and Inquiry-Based Learning: The Revitalization of the Humboldtian Ideals

ERIC Educational Resources Information Center

Zupanc, Gunther K. H.

2012-01-01

The past few decades have witnessed an increasing separation of research and teaching, particularly in the area of undergraduate education. Supporters of such a separation have argued that involvement of undergraduates in research is incompatible with the idea of the research university. However, one of the founding principles of the research…
Undergraduate research as curriculum.

PubMed

Dolan, Erin L

2017-07-08

To date, national interests, policies, and calls for transformation of undergraduate education have been the main drivers of research integration into the undergraduate curriculum, briefly described here. The New Horizons in Biochemistry and Molecular Biology Education conference at the Weizmann Institute of Science (Israel) this fall presents an exciting opportunity to discuss integration of undergraduate research into the curriculum and other cutting-edge topics in biochemistry and molecular biology education from a cross-national perspective. I look forward to exploring prospects for international collaboration on research and development of course-based undergraduate research experiences and on STEM education in general. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):293-298, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.
Teaching and Research at Undergraduate Institutions

NASA Astrophysics Data System (ADS)

Garg, Shila

2006-03-01

My own career path has been non-traditional and I ended up at a primarily undergraduate institution by pure accident. However, teaching at a small college has been extremely rewarding to me, since I get to know and interact with my students, have an opportunity to work with them one-on-one and promote their intellectual growth and sense of social responsibility. One of the growing trends at undergraduate institutions in the past decade has been the crucial role of undergraduate research as part of the teaching process and the training of future scientists. There are several liberal arts institutions that expect research-active Faculty who can mentor undergraduate research activities. Often faculty members at these institutions consider their roles as teacher-scholars with no boundary between these two primary activities. A researcher who is in touch with the developments in his/her own field and contributes to new knowledge in the field is likely to be a more exciting teacher in the classroom and share the excitement of discovery with the students. At undergraduate institutions, there is generally very good support available for faculty development projects in both teaching and research. Often, there is a generous research leave program as well. For those who like advising and mentoring undergraduates and a teaching and learning centered paradigm, I will recommend a career at an undergraduate institution. In my presentation, I will talk about how one can prepare for such a career.
Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization.

PubMed

Chow, Shing Fung; Wan, Ka Yee; Cheng, Kwok Kin; Wong, Ka Wai; Sun, Changquan Calvin; Baum, Larry; Chow, Albert Hee Lum

2015-08-01

The influence of critical operating parameters on the Flash Nanoprecipitation (FNP) and resulting material properties of curcumin (CUR) nanoparticles has been evaluated using a confined impinging jets-with-dilution mixer (CIJ-D-M). It has been shown that the mixing rate, molecular weight of polymeric stabilizer (i.e., polyethylene glycol-b-poly(dl-lactide) di-block copolymer; PEG-PLA) and drug-to-copolymer mass ratio all exert a significant impact on the particle size and stability of the generated nanosuspensions. The attainable mean particle size and span of the nanoparticles through optimization of these process parameters were approximately 70nm and 0.85 respectively. However, the optimized nanosuspension was only stable for about two hours after preparation. Co-formulation with polyvinylpyrrolidone (PVP) substantially extended the product lifespan to 5days at ambient conditions and two weeks at 4°C. Results from zeta potential measurement and X-ray photoelectron spectroscopy (XPS) suggested that the enhanced stability is probably due to the formation of an additional protective barrier by PVP around the particle surface, thereby suppressing the dissociation of PEG-PLA from the particles and preventing CUR leakage from inside. Long-term storage stability (>1year) could be achieved by lyophilization of the optimized nanosuspension with Kleptose (hydroxypropyl-β-cyclodextrin), which was shown to be the only effective lyoprotectant among all the ones tested for the CUR nanoparticles. At an optimal concentration of Kleptose (1.25% w/v), the redispersibility (Sf/Si; ratio of the final and initial particle sizes) and encapsulation efficiency of lyophilized CUR nanoparticles were about 1.22% and 94%, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.
Amphiphilic Peptide Nanorods Based on Oligo-Phenylalanine as a Biocompatible Drug Carrier.

PubMed

Song, Su Jeong; Lee, Seulgi; Ryu, Kyoung-Seok; Choi, Joon Sig

2017-09-20

Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH 3 F 8 (Arg-His 3 -Phe 8 ), as a drug-delivery carrier. Arginine is an essential amino acid in typical cell-penetration peptides, and histidine induces endo- and lysosomal escape because of its proton sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for stable self-assembly and drug encapsulation. The self-assembled structure of RH 3 F 8 showed nanorod-shaped morphology, positive surface charge, and retained formation in water for 35 days. RH 3 F 8 , labeled with Nile Red, showed high cellar uptake and accumulation in both cytoplasm and nucleus. The RH 3 F 8 nanorods demonstrated negligible cytotoxicity, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and hemolysis assays. To confirm the efficiency of drug delivery, curcumin was encapsulated in the RH 3 F 8 nanorod system (RH 3 F 8 -Cur). RH 3 F 8 -Cur showed high encapsulation efficiency (24.63%) under the conditions of 200 μM curcumin. The RH 3 F 8 -Cur retained nanoscale size and positive surface charge, similar to those of the empty RH 3 F 8 nanorods. RH 3 F 8 -Cur displayed a robust anticancer effect in HeLa and A549 cells, and inhibited the proliferation of cancer cells in a zebrafish model. These results indicate that the RH 3 F 8 nanorods may be a promising candidate for a safe and effective drug-delivery system.
Morphological and Biochemical Features of Cerebellar Cortex After Exposure to Zinc Oxide Nanoparticles: Possible Protective Role of Curcumin.

PubMed

Amer, Mona G; Karam, Rehab A

2018-03-25

Zinc oxide nanoparticles (ZnONPs) are widely used in the last decades. Therefore, investigation of its neurotoxic effect is important. This work aimed to investigate the potential adverse effects of ZnONPs on rat's cerebellar cortex and the possible neuroprotective role of curcumin (Cur). Forty male albino rats were randomly divided into four equal groups. Two groups were injected with ZnONPs and one group was previously received Cur before ZnONPs. At the end of the experiment, cerebellar tissue samples were prepared for histological, morphometric, immunohistochemical study, and tissue levels of oxidative stress markers and cytokine analysis. cerebellar damage is clearly visible with ZnONPs. Degeneration, loss, disorganization of cerebellar neurons was observed. Histopathological degeneration of Purkinje and granular cells together with loss of Nissl substance, astrocyte gliosis, and affection of cerebellar blood brain barrier were detected. Moreover, an apoptotic marker (caspase-3) was significantly expressed in Purkinje and granular layers together with elevated gene expression of P53 and COX-2 in cerebellar tissue of ZnONPs intoxicated group. Astrocyte gliosis and inflammatory markers IL-1, IL-6, and TNF-α were expressed significantly in ZnONPs intoxicated cerebellum. These changes were associated with evidence of cerebellar oxidative stress. Strikingly, treatment with Cur together with ZnONPs recorded morphological improvement, with increased number of Purkinje cells and decreased caspase +ve cells. These findings were confirmed by morphometric and statistical analysis. Cur ameliorates the deterious effect of ZnONPs on the cerebellar cortex through its antioxidant, antiapoptotic, and anti-inflammatory efficacies. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis.

PubMed

Nasra, Maha M A; Khiri, Heba M; Hazzah, Heba A; Abdallah, Ossama Y

2017-11-01

This study aimed to develop syringeable in-situ curcumin (cur) gel for the treatment of periodontal pockets as well as to evaluate the clinical efficacy of Cur in-situ gel formulation. Different in-situ gel formulations of Cur were prepared using 30% of pluronic F127, and 1% of carbopol P934. The formulations were evaluated regarding gelation temperature, pH, viscosity, syringeability study, in-vitro release and chemical stability of cur. The effect of aging of gel formulations for 3months in refrigerator was investigated. The selected formulation was clinically evaluated through the determination of probing depth, plaque index, and bleeding index at baseline and 1 month after application. The formulations showed accepted gelation temperature ranging from 28 to 34 °C and all had pH value of 4. The viscosity of the formulations at 4 °C ranged from 19 000 to 37 000 cP. All formulations were easily syringeable through 21 gauge needle at cold temperature. Curcumin stability during the release study was maintained. Aging showed no significant effect on release profile, drug content, or the pH after 3 months, while it showed a slight increase in viscosity with concomitant decrease in gelation temperature. Selected formulations delivered into periodontal pocket evaluated clinically showed to be effective. The treated group revealed that the adjunctive use of intracrevicular 2% curcumin in-situ gel adjunct to mechanical treatment in patients with adult periodontitis could aid in significant clinical reduction of probing depth, bleeding index, and to less extent of plaque. This indicates that curcumin in this novel drug delivery system is an excellent candidate for periodontal disease treatment.
Polyelectrolyte Complex Nanoparticles from Chitosan and Acylated Rapeseed Cruciferin Protein for Curcumin Delivery.

PubMed

Wang, Fengzhang; Yang, Yijie; Ju, Xingrong; Udenigwe, Chibuike C; He, Rong

2018-03-21

Curcumin is a polyphenol that exhibits several biological activities, but its low aqueous solubility results in low bioavailability. To improve curcumin bioavailability, this study has focused on developing a polyelectrolyte complexation method to form layer-by-layer assembled nanoparticles, for curcumin delivery, with positively charged chitosan (CS) and negatively charged acylated cruciferin (ACRU), a rapeseed globulin. Nanoparticles (NPs) were prepared from ACRU and CS (2:1) at pH 5.7. Three samples with weight of 5%, 10%, and 15% of curcumin, respectively, in ACRU/CS carrier were prepared. To verify the stability of the NPs, encapsulation efficiency and size of the 5% Cur-ACRU/CS NPs were determined at intervals of 5 days in a one month period. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, and differential scanning calorimetry confirmed the electrostatic interaction and hydrogen bond formation between the carrier and core. The result showed that hollow ACRU/CS nanocapsules (ACRU/CS NPs) and curcumin-loaded ACRU/CS nanoparticles (Cur-ACRU/CS NPs) were homogenized spherical with average sizes of 200-450 nm and zeta potential of +15 mV. Encapsulation and loading efficiencies were 72% and 5.4%, respectively. In vitro release study using simulated gastro (SGF) and intestinal fluids (SIF) showed controlled release of curcumin in 6 h of exposure. Additionally, the Cur-ACRU/CS NPs are nontoxic to cultured Caco-2 cells, and the permeability assay indicated that Cur-ACRU/CS NPs had improved permeability efficiency of free curcumin through the Caco-2 cell monolayer. The findings suggest that ACRU/CS NPs can be used for encapsulation and delivery of curcumin in functional foods.
PLGA-CTAB curcumin nanoparticles: Fabrication, characterization and molecular basis of anticancer activity in triple negative breast cancer cell lines (MDA-MB-231 cells).

PubMed

Meena, Ramovatar; Kumar, Sumit; Kumar, Raj; Gaharwar, Usha Singh; Rajamani, Paulraj

2017-10-01

Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells). In in-vitro drug release assay, Cur was released from CN by flicking diffusion and anomalous transport process. CN showed a higher cellular incorporation than free Cur resulted in higher cytotoxicity. Checking the anticancer activity at the molecular level, Cur has shown to induce the reactive oxygen species production that subsequently causes the DNA damage and resulting in p38-MAPK activation. The p38-MAPK induce the expression of p16 /INKK4a , p21 /waf1/cip1 and p53 resulting in a reduction in the level of CDK2, CDK4, cyclin D1 and cyclin E and subsequently cell cycle arrest at G1/S and G2/M phase. It also reduces the expression of DNA repair gene, i.e. BRCA1, BRCA2, Rad51, Rad50, Mre11 and NBS1 resulting in apoptosis induction due to persistent DNA damage. This study presents an effective delivery of curcumin in TNBC cancer cells and it could open the new frontiers in clinical cancer chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Urinary excretion of uric acid is negatively associated with albuminuria in patients with chronic kidney disease: a cross-sectional study.

PubMed

Li, Fengqin; Guo, Hui; Zou, Jianan; Chen, Weijun; Lu, Yijun; Zhang, Xiaoli; Fu, Chensheng; Xiao, Jing; Ye, Zhibin

2018-04-24

Increasing evidence has shown that albuminuria is related to serum uric acid. Little is known about whether this association may be interrelated via renal handling of uric acid. Therefore, we aim to study urinary uric acid excretion and its association with albuminuria in patients with chronic kidney disease (CKD). A cross-sectional study of 200 Chinese CKD patients recruited from department of nephrology of Huadong hospital was conducted. Levels of 24 h urinary excretion of uric acid (24-h Uur), fractional excretion of uric acid (FEur) and uric acid clearance rate (Cur) according to gender, CKD stages, hypertension and albuminuria status were compared by a multivariate analysis. Pearson and Spearman correlation and multiple regression analyses were used to study the correlation of 24-h Uur, FEur and Cur with urinary albumin to creatinine ratio (UACR). The multivariate analysis showed that 24-h Uur and Cur were lower and FEur was higher in the hypertension group, stage 3-5 CKD and macro-albuminuria group (UACR> 30 mg/mmol) than those in the normotensive group, stage 1 CKD group and the normo-albuminuria group (UACR< 3 mg/mmol) (all P < 0.05). Moreover, males had higher 24-h Uur and lower FEur than females (both P < 0.05). Multiple linear regression analysis showed that UACR was negatively associated with 24-h Uur and Cur (P = 0.021, P = 0.007, respectively), but not with FEur (P = 0.759), after adjusting for multiple confounding factors. Our findings suggested that urinary excretion of uric acid is negatively associated with albuminuria in patients with CKD. This phenomenon may help to explain the association between albuminuria and serum uric acid.
The sexual assault of undergraduate women at historically Black colleges and universities (HBCUs).

PubMed

Krebs, Christopher P; Barrick, Kelle; Lindquist, Christine H; Crosby, Carmen M; Boyd, Chimi; Bogan, Yolanda

2011-12-01

Although research has shown that undergraduate women are at high risk for experiencing sexual assault, little research has been conducted with undergraduate women who are attending a historically Black college or university (HBCU). The purpose of this research is to document the prevalence of different types of sexual assault among undergraduate women at HBCUs and make comparisons to data collected from undergraduate women at non-HBCUs. Data on sexual assault victimization were collected from 3,951 undergraduate women at HBCUs using a cross-sectional, web-based survey. These data are compared to data collected from 5,446 undergraduate women at non-HBCUs using the same research methods. Findings indicate that approximately 9.7% of undergraduate women at HBCUs report experiencing a completed sexual assault since entering college. This rate is considerably lower than the comparable rate obtained from undergraduate women at non-HBCUs (13.7%). This difference seems to be associated with differences in alcohol-use frequency. Perhaps undergraduate women at HBCUs drink alcohol much less frequently and are thus less likely to be sexually assaulted when they are incapacitated and unable to provide consent. Alcohol use frequency, while controlling for other factors, seems to have an independent association with the likelihood of an undergraduate woman being sexually assaulted. Implications for the creation and delivery of sexual assault risk reduction and prevention policies and programs are discussed.
Undergraduate Research as Engaged Student Learning

ERIC Educational Resources Information Center

Wolf, Lorraine W.

2018-01-01

This chapter discusses the impact of undergraduate research as a form of engaged student learning. It summarizes the gains reported in post-fellowship assessment essays acquired from students participating in the Auburn University Undergraduate Research Fellowship Program. The chapter also discusses the program's efforts to increase opportunities…
Student Effort in and Perceived Benefits from Undergraduate Research

ERIC Educational Resources Information Center

Salsman, Nicholas; Dulaney, Cynthia L.; Chinta, Ravi; Zascavage, Victoria; Joshi, Hem

2013-01-01

The benefits of student engagement in undergraduate research are well-recognized by many higher education institutions. Increased emphasis on undergraduate research in these institutions has taken many forms resulting in considerable differences across institutions ranging from "light touch" to "heavy duty" involvement of…
Cultivating and Nurturing Undergraduate IS Research

ERIC Educational Resources Information Center

Tams, Stefan

2014-01-01

Assurance of student motivation and retention is a central challenge for Information Systems faculty. A promising means of stimulating interest in the Information Systems major and in subsequent graduate degree programs is undergraduate Information Systems research. Undergraduate Information Systems research allows students to engage more deeply…
Enhancing Student Learning of Research Methods through the Use of Undergraduate Teaching Assistants

ERIC Educational Resources Information Center

Crowe, Jessica; Ceresola, Ryan; Silva, Tony

2014-01-01

By using a quasi-experimental design, in this study, we test the effect of undergraduate teaching assistants on student learning. Data were collected from 170 students enrolled in four sections of a quantitative research methods course, two sections without undergraduate teaching assistants and two sections with undergraduate teaching assistants,…
Undergraduate Research and Academic Archives: Instruction, Learning and Assessment

ERIC Educational Resources Information Center

Krause, Magia G.

2010-01-01

Colleges and universities are increasingly investing resources to promote undergraduate research. Undergraduate research can be broadly defined to incorporate scientific inquiry, creative expression, and scholarship with the result of producing original work. Academic archives and special collections can play a vital role in the undergraduate…
Enhancing Undergraduate Teaching and Research with a "Drosophila" Virginizing System

ERIC Educational Resources Information Center

Venema, Dennis R.

2006-01-01

Laboratory exercises using "Drosophila" crosses are an effective pedagogical method to complement traditional lecture and textbook presentations of genetics. Undergraduate thesis research is another common setting for using "Drosophila." A significant barrier to using "Drosophila" for undergraduate teaching or research is the time and skill…
Making the Most of Multi-Disciplinary Undergraduate Research Conferences

ERIC Educational Resources Information Center

Hill, Jennifer; West, Harry; Kneale, Pauline

2018-01-01

This is the second of two Directions articles, which together offer guidance to help the reader gain the maximum benefit from participating in institutional and national multi-disciplinary undergraduate research conferences. The earlier article introduced undergraduate research conferences, summarized the key benefits of participating in such…
Developing Students, Developing Faculty: Incompatible or Compatible Goals?

ERIC Educational Resources Information Center

Ware, Mark E.; Davis, Stephen F.; Smith, Randolph A.

Grounding students in research methodology is at the core of the undergraduate curriculum. Students usually conduct individual projects in the experimental psychology or research methods courses, and most undergraduate courses in the psychology curriculum contain a strong research component. The opportunities and benefits for undergraduate student…
The Influence of Materials Science and Engineering Undergraduate Research Experiences on Public Communication Skills

ERIC Educational Resources Information Center

Ing, Marsha; Fung, Wenson W.; Kisailus, David

2013-01-01

Communicating research findings with others is a skill essential to the success of future STEM professionals. However, little is known about how this skill can be nurtured through participating in undergraduate research. The purpose of this study is to quantify undergraduate participation in research in a materials science and engineering…
Undergraduate Research as a Fate Accompli: Innovation and Evolution of a Student Conference in Business

ERIC Educational Resources Information Center

Buff, Cheryl L.; Devasagayam, Raj

2016-01-01

The benefits of undergraduate research continue to receive academic attention and it is becoming an engaged learning practice present on many college campuses today. As research participation grows, an opportunity exists to showcase the work being accomplished and to use this public presentation to foster a culture of undergraduate research on…
Mentored undergraduate research in the geosciences

NASA Astrophysics Data System (ADS)

Judge, Shelley; Pollock, Meagen; Wiles, Greg; Wilson, Mark

2012-09-01

There is little argument about the merits of undergraduate research, but it can seem like a complex, resource-intensive endeavor [e.g., Laursen et al., 2010; Lopatto, 2009; Hunter et al., 2006]. Although mentored undergraduate research can be challenging, the authors of this feature have found that research programs are strengthened when students and faculty collaborate to build new knowledge. Faculty members in the geology department at The College of Wooster have conducted mentored undergraduate research with their students for more than 60 years and have developed a highly effective program that enhances the teaching, scholarship, and research of our faculty and provides life-changing experiences for our students. Other colleges and universities have also implemented successful mentored undergraduate research programs in the geosciences. For instance, the 18 Keck Geology Consortium schools (http://keckgeology.org/), Princeton University, and other institutions have been recognized for their senior capstone experiences by U.S. News & World Report.
Cultivating the scientific research ability of undergraduate students in teaching of genetics.

PubMed

Xing, Wan-jin; Morigen, Morigen

2016-11-20

The classroom is the main venue for undergraduate teaching. It is worth pondering how to cultivate undergraduate's research ability in classroom teaching. Here we introduce the practices and experiences in teaching reform in genetics for training the research quality of undergraduate students from six aspects: (1) constructing the framework for curriculum framework systematicaly, (2) using the teaching content to reflect research progress, (3) explaining knowledge points with research activities, (4) explaining the scientific principles and experiments with PPT animation, (5) improving English reading ability through bilingual teaching, and (6) testing students' analysing ability through examination. These reforms stimulate undergraduate students' enthusiasm for learning, cultivate their ability to find, analyze and solve scientific problems, and improve their English reading and literature reviewing capacity, which lay a foundation for them to enter the field of scientific research.
(De)Constructing the Undergraduate Research Experience in an Environmental Geochemistry Lab (Invited)

NASA Astrophysics Data System (ADS)

Kim, C. S.

2013-12-01

Maintaining a productive research lab at the undergraduate level requires a savvy combination of internal organization, high (but realistic) expectations, and adaptation of one's research interests into semester- and summer-length projects. Several key strategies can help achieve the goal of building a lab culture that both enriches students' academic experiences and advances one's own scholarly research and visibility. Foremost among these is the need to maintain momentum and preserve institutional knowledge in an environment where undergraduate students' lifetime in an individual lab may only last a year or two. Examples from the Environmental Geochemistry Lab at Chapman University (www.chapman.edu/envgeo) developed over several years and with 40+ undergraduate students will be presented which can be transferable to other faculty research labs in the earth sciences. Approaches to writing successful external research grant proposals at a primarily undergraduate institution (PUI) and strategies for both personal and institutional time management/savings will also be discussed, with a focus on new models at Chapman offered to further incentivize faculty involvement in undergraduate research.
The Role of Student-Advisor Interactions in Apprenticing Undergraduate Researchers into a Scientific Community of Practice

NASA Astrophysics Data System (ADS)

Thiry, Heather; Laursen, Sandra L.

2011-12-01

Among science educators, current interest in undergraduate research (UR) is influenced both by the traditional role of the research apprenticeship in scientists' preparation and by concerns about replacing the current scientific workforce. Recent research has begun to demonstrate the range of personal, professional, and intellectual benefits for STEM students from participating in UR, yet the processes by which student-advisor interactions contribute to these benefits are little understood. We employ situated learning theory (Lave and Wenger, Situated learning: legitimate peripheral participation, Cambridge University Press, Cambridge in 1991) to examine the role of student-advisor interactions in apprenticing undergraduate researchers, particularly in terms of acculturating students to the norms, values, and professional practice of science. This qualitative study examines interviews with a diverse sample of 73 undergraduate research students from two research-extensive institutions. From these interviews, we articulate a continuum of practices that research mentors employed in three domains to support undergraduate scientists-in-training: professional socialization, intellectual support, and personal/emotional support. The needs of novice students differed from those of experienced students in each of these areas. Novice students needed clear expectations, guidelines, and orientation to their specific research project, while experienced students needed broader socialization in adopting the traits, habits, and temperament of scientific researchers. Underrepresented minority students, and to a lesser extent, women, gained confidence from their interactions with their research mentors and broadened their future career and educational possibilities. Undergraduate research at research-extensive universities exemplifies a cycle of scientific learning and practice where undergraduate researchers are mentored by graduate students and postdoctoral researchers, who are themselves apprentices to faculty members. As such, research mentors of undergraduate students should be aware of the dual scientific and educational aspects of their advising role and its significance in shaping students' identities and career trajectories.
Interdisciplinary Biomathematics: Engaging Undergraduates in Research on the Fringe of Mathematical Biology

ERIC Educational Resources Information Center

Fowler, Kathleen; Luttman, Aaron; Mondal, Sumona

2013-01-01

The US National Science Foundation's (NSF's) Undergraduate Biology and Mathematics (UBM) program significantly increased undergraduate research in the biomathematical sciences. We discuss three UBM-funded student research projects at Clarkson University that lie at the intersection of not just mathematics and biology, but also other fields. The…

Reliability Estimates for Undergraduate Grade Point Average

ERIC Educational Resources Information Center

Westrick, Paul A.

2017-01-01

Undergraduate grade point average (GPA) is a commonly employed measure in educational research, serving as a criterion or as a predictor depending on the research question. Over the decades, researchers have used a variety of reliability coefficients to estimate the reliability of undergraduate GPA, which suggests that there has been no consensus…
Telepresence-Enabled Remote Fieldwork: Undergraduate Research in the Deep Sea

ERIC Educational Resources Information Center

Stephens, A. Lynn; Pallant, Amy; McIntyre, Cynthia

2016-01-01

Deep-sea research is rarely available to undergraduate students. However, as telepresence technology becomes more available, doors may open for more undergraduates to pursue research that includes remote fieldwork. This descriptive case study is an initial investigation into whether such technology might provide a feasible opportunity for…
Pathways to Undergraduate Research Experiences: A Multi-Institutional Study

ERIC Educational Resources Information Center

Mahatmya, Duhita; Morrison, Janet; Jones, Rebecca M.; Garner, Pamela W.; Davis, Shannon N.; Manske, Jill; Berner, Nancy; Johnson, Ann; Ditty, Jayna

2017-01-01

The positive impact of undergraduate research experiences on students' post-secondary success is well-documented. However, these conclusions are drawn from undergraduate students who already participate; very little research has explored the pathways by which students enter these experiences. Using data from a multi-institutional survey, we…
Learning by Doing: The Challenge of Engaging Undergraduates in Economics Research

ERIC Educational Resources Information Center

Brunnermeier, Smita

2017-01-01

This article describes strategies developed at Princeton University to foster and promote research by all undergraduate students majoring in economics. It describes core features of the undergraduate research program and provides tangible recommendations for addressing resource constraints, and for incentivizing faculty advisors and students to…
Ideas and Approaches for Teaching Undergraduate Research Methods in the Health Sciences

ERIC Educational Resources Information Center

Peachey, Andrew A.; Baller, Stephanie L.

2015-01-01

Training in research methodology is becoming more commonly expected within undergraduate curricula designed to prepare students for entry into graduate allied health programs. Little information is currently available about pedagogical strategies to promote undergraduate students' learning of research methods, and less yet is available discussing…
Student Perceptions on Live-Case Projects: Undergraduate Marketing Research

ERIC Educational Resources Information Center

Gundala, Raghava Rao; Singh, Mandeep; Baldwin, Andrew

2014-01-01

This paper is an investigation into undergraduate students' perceptions on use of live projects as a teaching pedagogy in marketing research courses. Students in undergraduate marketing research courses from fall 2009 to spring 2013 completed an online questionnaire consisting of 17 items. The results suggested that student understanding of…
Demand for Interdisciplinary Laboratories for Physiology Research by Undergraduate Students in Biosciences and Biomedical Engineering

ERIC Educational Resources Information Center

Clase, Kari L.; Hein, Patrick W.; Pelaez, Nancy J.

2008-01-01

Physiology as a discipline is uniquely positioned to engage undergraduate students in interdisciplinary research in response to the 2006-2011 National Science Foundation Strategic Plan call for innovative transformational research, which emphasizes multidisciplinary projects. To prepare undergraduates for careers that cross disciplinary…
Preparing for Multi-Disciplinary Undergraduate Research Conferences

ERIC Educational Resources Information Center

Hill, Jennifer; West, Harry; Kneale, Pauline

2018-01-01

National undergraduate research conferences have been commonplace in the US for many years e.g. the National Conference on Undergraduate Research (NCUR), and are becoming more frequent elsewhere. Alongside national conferences many universities hold their own events, which are often institution-wide, so as to appeal to a large proportion of their…
Research Experiences of Undergraduate Students at a Comprehensive University

ERIC Educational Resources Information Center

Tan, Emily B.

2007-01-01

Narrative inquiry was utilized to allow undergraduate students involved in an undergraduate research course to narrate their experiences in their research undertakings under the guidance of their respective mentors. A total of four focus groups representing the Bachelor of Arts and Letters, Bachelor of Commerce, Bachelor of Secondary Education,…
Faculty Workload Issues Connected to Undergraduate Research

ERIC Educational Resources Information Center

Free, Rhona; Griffith, Suzanne; Spellman, Bill

2015-01-01

This chapter delineates the consortial activities of the Council of Public Liberal Arts Colleges (COPLAC) to explore models of undergraduate research and to address the impact of undergraduate research on faculty workload. The significant progress made on the member campus of the University of Wisconsin-Superior over the last 10 years is…
Teaching Undergraduate Research: The One-Room Schoolhouse Model

ERIC Educational Resources Information Center

Henderson, LaRhee; Buising, Charisse; Wall, Piper

2008-01-01

Undergraduate research in the biochemistry, cell, and molecular biology program at Drake University uses apprenticeship, cooperative-style learning, and peer mentoring in a cross-disciplinary and cross-community educational program. We call it the one-room schoolhouse approach to teaching undergraduate research. This approach is cost effective,…
Engaging Students: An Authentic Undergraduate Research Experience

ERIC Educational Resources Information Center

Alderton, Elizabeth; Manzi, Michelina

2017-01-01

Engaging students in valuable undergraduate research can be an arduous task to craft outside of the regular schedule of both staff and students. This paper describes a successful research experience that was part of an ongoing methods class for undergraduate pre-service education students. Participants simultaneously engaged in community service…
Undergraduate Research Experience for STEM Students: Efforts and Outcomes

ERIC Educational Resources Information Center

Zhang, Chuanlei; Swaid, Samar

2017-01-01

Undergraduate research for STEM students involves students who are attending college or universities pursuing a bachelor's degree, majoring in fields related to Science, Technology, Engineering and Mathematics (STEM). Research experience for STEM undergraduates has been viewed as a positive experience that has several benefits such as developing…
Tsinghua-Johns Hopkins Joint Center for Biomedical Engineering Research: scientific and cultural exchange in undergraduate engineering.

PubMed

Wisneski, Andrew D; Huang, Lixia; Hong, Bo; Wang, Xiaoqin

2011-01-01

A model for an international undergraduate biomedical engineering research exchange program is outlined. In 2008, the Johns Hopkins University in collaboration with Tsinghua University in Beijing, China established the Tsinghua-Johns Hopkins Joint Center for Biomedical Engineering Research. Undergraduate biomedical engineering students from both universities are offered the opportunity to participate in research at the overseas institution. Programs such as these will not only provide research experiences for undergraduates but valuable cultural exchange and enrichment as well. Currently, strict course scheduling and rigorous curricula in most biomedical engineering programs may present obstacles for students to partake in study abroad opportunities. Universities are encouraged to harbor abroad opportunities for undergraduate engineering students, for which this particular program can serve as a model.
Influences on Faculty Willingness to Mentor Undergraduate Students from Another University as Part of an Interinstitutional Research Training Program

PubMed Central

Morales, Danielle X.; Grineski, Sara E.; Collins, Timothy W.

2016-01-01

In 2014, the National Institutes of Health invested $31 million in 10 primary institutions across the United States through the Building Undergraduate Infrastructure Leading to Diversity (BUILD) program; one requirement of BUILD is sending undergraduate trainees from those primary institutions to partner institutions for research experiences. Mechanisms like BUILD are designed to broaden research opportunities for students, especially those from underrepresented backgrounds. However, to our knowledge, no studies have examined faculty willingness to mentor undergraduates from other institutions through structured training programs. Survey data from 536 faculty members at 13 institutions were collected in Fall 2013 and analyzed using multiple statistical techniques. Results show that faculty who valued the opportunity to increase diversity in the academy and those who believed that mentoring undergraduates benefited their own research expressed greater willingness to serve as research mentors to visiting undergraduates, and faculty who perceived that they did not have the ability to accommodate additional students expressed less willingness to do so. Most respondents viewed student and faculty incentives as motivating factors in their willingness to mentor, but their perspectives on different types of incentives varied based on faculty career stage, discipline, and research funding status. Results have important implications for designing multi-institutional undergraduate research training programs. PMID:27521237
Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis

PubMed Central

Falah, Rabah Rashad; Talib, Wamidh H.; Shbailat, Seba Jamal

2017-01-01

Background: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. Materials and methods: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c mice with EMT6/P cells and examining tumor growth and apoptosis induction in tumor sections. Furthermore, serum levels of different cytokines and transaminases and creatinine were measured to detect the immune response and toxicity, respectively. Results: The combination treatment exhibited the highest effects against tumor proliferation and growth. It significantly reduced VEGF expression, induced Trp53 independent apoptosis, triggered Th2 immune response and showed no toxicity. Conclusion: The combination can be a potential therapeutic option to treat breast cancer. However, further testing is needed to measure the exact serum levels of MET and CUR and to further explain the obtained results. PMID:28491145
Heat transfer nanofluid based on curly ultra-long multi-wall carbon nanotubes

NASA Astrophysics Data System (ADS)

Boncel, Sławomir; Zniszczoł, Aurelia; Pawlyta, Mirosława; Labisz, Krzysztof; Dzido, Grzegorz

2018-02-01

The main challenge in the use of multi-wall carbon nanotube (MWCNT) as key components of nanofluids is to transfer excellent thermal properties from individual nanotubes into the bulk systems. We present studies on the performance of heat transfer nanofluids based on ultra-long ( 2 mm), curly MWCNTs - in the background of various other nanoC-sp2, i.e. oxidized MWCNTs, commercially available Nanocyl™ MWCNTs and spherical carbon nanoparticles (SCNs). The nanofluids prepared via ultrasonication from water and propylene glycol were studied in terms of heat conductivity and heat transfer in a scaled up thermal circuit containing a copper helical heat exchanger. Ultra-long curly MWCNT (1 wt.%) nanofluids (stabilized with Gum Arabic in water) emerged as the most thermally conducting ones with a 23-30%- and 39%-enhancement as compared to the base-fluids for water and propylene glycol, respectively. For turbulent flows ( Re = 8000-11,000), the increase of heat transfer coefficient for the over-months stable 1 wt.% ultra-long MWCNT nanofluid was found as high as >100%. The findings allow to confirm that longer MWCNTs are promising solid components in nanofluids and hence to predict their broader application in heat transfer media.
From Faculty for Undergraduate Neuroscience: Encouraging Innovation in Undergraduate Neuroscience Education by Supporting Student Research and Faculty Development

ERIC Educational Resources Information Center

Hardwick, Jean C.; Kerchner, Michael; Lom, Barbara; Ramirez, Julio J.; Wiertelak, Eric P.

2006-01-01

This article features the organization Faculty for Undergraduate Neuroscience. FUN was established by a group of neuroscientists dedicated to innovation and excellence in undergraduate neuroscience education and research. In the years since its inception, FUN has grown into a dynamic organization making a significant impact on the quality of…
Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

PubMed Central

Busari, Zulaikha A.; Dauda, Kabiru A.; Morenikeji, Olajumoke A.; Afolayan, Funmilayo; Oyeyemi, Oyetunde T.; Meena, Jairam; Sahu, Debasis; Panda, Amulya K.

2017-01-01

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p < 0.05) in exposed RAW 264.7 cell line. The cell viability was, however, higher in Cur-PLGA nanoparticles than in free curcumin at lower concentrations (p > 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration. PMID:28932197
Increasing Research Productivity in Undergraduate Research Experiences: Exploring Predictors of Collaborative Faculty-Student Publications.

PubMed

Morales, Danielle X; Grineski, Sara E; Collins, Timothy W

2017-01-01

Little attention has been paid to understanding faculty-student productivity via undergraduate research from the faculty member's perspective. This study examines predictors of faculty-student publications resulting from mentored undergraduate research, including measures of faculty-student collaboration, faculty commitment to undergraduate students, and faculty characteristics. Generalized estimating equations were used to analyze data from 468 faculty members across 13 research-intensive institutions, collected by a cross-sectional survey in 2013/2014. Results show that biomedical faculty mentors were more productive in publishing collaboratively with undergraduate students when they worked with students for more than 1 year on average, enjoyed teaching students about research, had mentored Black students, had received more funding from the National Institutes of Health, had a higher H-index scores, and had more years of experience working in higher education. This study suggests that college administrators and research program directors should strive to create incentives for faculty members to collaborate with undergraduate students and promote faculty awareness that undergraduates can contribute to their research. © 2017 D. X. Morales et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Undergraduate Biology Lab Courses: Comparing the Impact of Traditionally Based "Cookbook" and Authentic Research-Based Courses on Student Lab Experiences

ERIC Educational Resources Information Center

Brownell, Sara E.; Kloser, Matthew J.; Fukami, Tadishi; Shavelson, Rich

2012-01-01

Over the past decade, several reports have recommended a shift in undergraduate biology laboratory courses from traditionally structured, often described as "cookbook," to authentic research-based experiences. This study compares a cookbook-type laboratory course to a research-based undergraduate biology laboratory course at a Research 1…
The Conundrum of Social Class: Disparities in Publishing among STEM Students in Undergraduate Research Programs at a Hispanic Majority Institution

ERIC Educational Resources Information Center

Grineski, Sara; Daniels, Heather; Collins, Timothy; Morales, Danielle X.; Frederick, Angela; Garcia, Marilyn

2018-01-01

Research on the science, technology, engineering, and math (STEM) student development pipeline has largely ignored social class and instead examined inequalities based on gender and race. We investigate the role of social class in undergraduate student research publications. Data come from a sample of 213 undergraduate research participants…
Introducing Research Methods to Undergraduate Majors Through an On-Campus Observatory with The University of Toledo's Ritter Observatory

NASA Astrophysics Data System (ADS)

Richardson, Noel; Hardegree-Ullman, Kevin; Bjorkman, Jon Eric; Bjorkman, Karen S.; Ritter Observing Team

2017-01-01

With a 1-m telescope on the University of Toledo (OH) main campus, we have initiated a grad student-undergraduate partnership to help teach the undergraduates observational methods and introduce them to research through peer mentorship. For the last 3 years, we have trained up to 21 undergraduates (primarily physics/astronomy majors) in a given academic semester, ranging from freshman to seniors. Various projects are currently being conducted by undergraduate students with guidance from graduate student mentors, including constructing three-color images, observations of transiting exoplanets, and determination of binary star orbits from echelle spectra. This academic year we initiated a large group research project to help students learn about the databases, journal repositories, and online observing tools astronomers use for day-to-day research. We discuss early inclusion in observational astronomy and research of these students and the impact it has on departmental retention, undergraduate involvement, and academic success.
NSF Support for Physics at the Undergraduate Level: A View from Inside

NASA Astrophysics Data System (ADS)

McBride, Duncan

2015-03-01

NSF has supported a wide range of projects in physics that involve undergraduate students. These projects include NSF research grants in which undergraduates participate; Research Experiences for Undergraduates (REU) centers and supplements; and education grants that range from upper-division labs that may include research, to curriculum development for upper- and lower-level courses and labs, to courses for non-majors, to Physics Education Research (PER). The NSF Divisions of Physics, Materials Research, and Astronomy provide most of the disciplinary research support, with some from other parts of NSF. I recently retired as the permanent physicist in NSF's Division of Undergraduate Education (DUE), which supports the education grants. I was responsible for a majority of DUE's physics grants and was involved with others overseen by a series of physics rotators. There I worked in programs entitled Instrumentation and Laboratory Improvement (ILI); Course and Curriculum Development (CCD); Course, Curriculum, and Laboratory Improvement (CCLI); Transforming Undergraduate STEM Education (TUES); and Improving Undergraduate STEM Education (IUSE). NSF support has enabled physics Principal Investigators to change and improve substantially the way physics is taught and the way students learn physics. The most important changes are increased undergraduate participation in physics research; more teaching using interactive engagement methods in classes; and growth of PER as a legitimate field of physics research as well as outcomes from PER that guide physics teaching. In turn these have led, along with other factors, to students who are better-prepared for graduate school and work, and to increases in the number of undergraduate physics majors. In addition, students in disciplines that physics directly supports, notably engineering and chemistry, and increasingly biology, are better and more broadly prepared to use their physics education in these fields. I will describe NSF support for undergraduate physics with both statistics and examples. In addition I will talk about trends in support for undergraduate physics at NSF and speculate about directions such support might go. Contents of this paper reflect the opinions of the author and do not necessarily reflect those of the National Science Foundation.
AGU Activities to Promote Undergraduate Research

NASA Astrophysics Data System (ADS)

Grove, K.; Johnson, R.; Giesler, J.

2001-05-01

A primary goal of the AGU Committee on Education and Human Resources (CEHR) is to significantly increase the participation of undergraduate students at AGU meetings. Involving students in scientific meetings at this level of their education helps them to better prepare for graduate school and for a career in the geophysical sciences. Ongoing CEHR activities to promote undergraduate participation include: (1) sponsoring technical sessions to showcase undergraduate research; (2) sponsoring sessions about careers and other topics of special interest to students; (3) sponsoring workshops to inform faculty about doing research with undergraduates; (4) sponsoring meeting events to partner graduate student mentors with first-time undergraduate attendees; (5) working with sections to create situations where undergraduates and section scientists can interact; (6) creating a guide for first-time meeting attendees; (7) sponsoring an Academic Recruiting Forum at meetings to connect undergraduates with geophysical graduate programs; (8) running a Career Center at meetings to connect students and employers; (9) raising funds for more travel grants to provide more student support to attend meetings; (10) developing a listserve to inform AGU members about opportunities to do research with undergraduates and to involve more members in mentoring activities; and (11) collecting data, such as career outcomes and demographic characteristics of recent Ph.D. recipients, that are of interest to students.
Development of a structured undergraduate research experience: Framework and implications.

PubMed

Brown, Anne M; Lewis, Stephanie N; Bevan, David R

2016-09-10

Participating in undergraduate research can be a pivotal experience for students in life science disciplines. Development of critical thinking skills, in addition to conveying scientific ideas in oral and written formats, is essential to ensuring that students develop a greater understanding of basic scientific knowledge and the research process. Modernizing the current life sciences research environment to accommodate the growing demand by students for experiential learning is needed. By developing and implementing a structured, theory-based approach to undergraduate research in the life sciences, specifically biochemistry, it has been successfully shown that more students can be provided with a high-quality, high-impact research experience. The structure of this approach allowed students to develop novel, independent projects in a computational molecular modeling lab. Students engaged in an experience in which career goals, problem-solving skills, time management skills, and independence in a research lab were developed. After experiencing this approach to undergraduate research, students reported feeling challenged to think critically and prepared for future career paths. The approach allowed for a progressive learning environment where more undergraduate students could participate in publishable research. Future areas for development include implementation in a bench-top lab and extension to disciplines beyond biochemistry. In this study, it has been shown that utilizing the structured approach to undergraduate research could allow for more students to experience undergraduate research and develop into more confident, independent life scientists well prepared for graduate schools and professional research environments. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):463-474, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.
Faculty Motivation to Mentor Students through Undergraduate Research Programs: A Study of Enabling and Constraining Factors

ERIC Educational Resources Information Center

Morales, Danielle X.; Grineski, Sara E.; Collins, Timothy W.

2017-01-01

Undergraduate research experiences are a "high impact" educational practice that confer benefits to students. However, little attention has been paid to understanding faculty motivation to mentor undergraduate students through research training programs, even as the number of programs has grown, requiring increasing numbers of faculty…
Impact of Undergraduate Research on Academic Performance, Educational Planning, and Career Development

ERIC Educational Resources Information Center

Kinkel, Doreen H.; Henke, Scott E.

2006-01-01

An undergraduate research mentoring program (URMP), initiated at Texas A&M University-Kingsville, was developed (1) to aid undergraduate wildlife students in the design, conduct, and analysis of original research projects; and (2) to encourage students to become effective written and oral communicators by preparing a manuscript of their…
The Contribution of Qualitative Research Towards the Issues Affecting Female Undergraduate Engineering Students

ERIC Educational Resources Information Center

Duggan, Louise Maria

2015-01-01

This article explores the use of qualitative research methods towards our understanding of the issues affecting female undergraduate engineers. As outlined in this article female engineering students face many challenges during their undergraduate studies. Qualitative research methods provide an opportunity to gain a deeper understanding of the…
Interpreting Undergraduate Research Posters in the Literature Classroom

ERIC Educational Resources Information Center

Manarin, Karen

2016-01-01

This essay explores the use of undergraduate research posters in English literature classrooms; at the same time, it argues for a scholarship of teaching and learning responsive to how meaning is constructed in the arts and humanities. Our scholarly practice requires interaction with texts and with each other, yet the undergraduate research paper…
Ten Time-Saving Tips for Undergraduate Research Mentors

ERIC Educational Resources Information Center

Coker, Jeffrey Scott; Davies, Eric

2006-01-01

Undergraduate research experiences can be extremely valuable for students, but can also be very time-consuming for mentors. A series of surveys were administered to plant biologists during the last 4 years to understand the perspectives of mentors on training undergraduate and high school student researchers. The survey responses provided a wealth…
A Successful Model of Collaborative Undergraduate Research: A Multi-Faculty, Multi-Project, Multi-Institution Team Approach

ERIC Educational Resources Information Center

Woodzicka, Julie A.; Ford, Thomas E.; Caudill, Abbie; Ohanmamooreni, Alyna

2015-01-01

A collaborative research grant from the National Science Foundation allowed the first two authors to provide students at primarily undergraduate institutions with a multi-faculty, multi-institution team research experience. Teams of undergraduate students at Western Carolina University and Washington and Lee University collaborated with one…
Insights for Academic Developers from Three International Undergraduate Research Program Resources

ERIC Educational Resources Information Center

Allison, Meredith; Miller, Paul

2018-01-01

Undergraduate research is recognized as a high-impact educational practice (Kuh & O'Donnell, 2013), and increasingly it occurs world-wide in higher education, in particular in the United States, United Kingdom, and Australia. In each of these countries, undergraduate research is delivered through a variety of pedagogical approaches that…
Introducing Ethics to Chemistry Students in a "Research Experiences for Undergraduates" (REU) Program

ERIC Educational Resources Information Center

Hanson, Mark J.

2015-01-01

A three-day ethics seminar introduced ethics to undergraduate environmental chemistry students in the Research Experiences for Undergraduates (REU) program. The seminar helped students become sensitive to and understand the ethical and values dimensions of their work as researchers. It utilized a variety of resources to supplement lectures and…
Involving Undergraduate Students in Educational Research: Achieving Two Goals at Once.

ERIC Educational Resources Information Center

Staik, Irene M.; Rogers, Julia S.

In a relatively small, predominantly undergraduate university, it is often hard to find the time and resources to conduct educational research. One small liberal arts college, the University of Montevallo (Alabama), has addressed this problem by involving undergraduate psychology majors in collaboration in educational research with faculty. It is…
Advancing Space Sciences through Undergraduate Research Experiences at UC Berkeley's Space Sciences Laboratory - a novel approach to undergraduate internships for first generation community college students

NASA Astrophysics Data System (ADS)

Raftery, C. L.; Davis, H. B.; Peticolas, L. M.; Paglierani, R.

2015-12-01

The Space Sciences Laboratory at UC Berkeley launched an NSF-funded Research Experience for Undergraduates (REU) program in the summer of 2015. The "Advancing Space Sciences through Undergraduate Research Experiences" (ASSURE) program recruited heavily from local community colleges and universities, and provided a multi-tiered mentorship program for students in the fields of space science and engineering. The program was focussed on providing a supportive environment for 2nd and 3rd year undergraduates, many of whom were first generation and underrepresented students. This model provides three levels of mentorship support for the participating interns: 1) the primary research advisor provides academic and professional support. 2) The program coordinator, who meets with the interns multiple times per week, provides personal support and helps the interns to assimilate into the highly competitive environment of the research laboratory. 3) Returning undergraduate interns provided peer support and guidance to the new cohort of students. The impacts of this program on the first generation students and the research mentors, as well as the lessons learned will be discussed.
Do They Want to Stay or Do They Want to Return? The Stay Inclinations for Chinese Undergraduate Students in a Public Mid-West Research University

ERIC Educational Resources Information Center

Wang, Lu

2017-01-01

This study expands understanding of Chinese international undergraduate students' stay inclinations in the United States. It analyzed a sample of 247 Chinese undergraduate students from a public Midwestern research university during Spring 2017. This study compared the differences in stay inclinations between Chinese undergraduate students who…
Incorporating "Ethics in Science" into a Summer Undergraduate Research Program.

ERIC Educational Resources Information Center

Shachter, Amy M.; McNelis, Brian J.; Shanks, Thomas

1999-01-01

Describes a program at Santa Clara University, California where undergraduates participated in weekly Ethics in Science discussions while conducting scientific research. The program was successful in improving the ethical sensitivity, judgment, and commitment of the undergraduates. (WRM)
Journal of Undergraduate Research, Volume IX, 2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stiner, K. S.; Graham, S.; Khan, M.

Each year more than 600 undergraduate students are awarded paid internships at the Department of Energy’s (DOE) National Laboratories. Th ese interns are paired with research scientists who serve as mentors in authentic research projects. All participants write a research abstract and present at a poster session and/or complete a fulllength research paper. Abstracts and selected papers from our 2007–2008 interns that represent the breadth and depth of undergraduate research performed each year at our National Laboratories are published here in the Journal of Undergraduate Research. The fields in which these students worked included: Biology; Chemistry; Computer Science; Engineering; Environmentalmore » Science; General Science; Materials Science; Medical and Health Sciences; Nuclear Science; Physics; Science Policy; and Waste Management.« less
Monitoring undergraduate student needs and activities at Experimental Biology: APS pilot survey.

PubMed

Nichols, Nicole L; Ilatovskaya, Daria V; Matyas, Marsha L

2017-06-01

Life science professional societies play important roles for undergraduates in their fields and increasingly offer membership, fellowships, and awards for undergraduate students. However, the overall impacts of society-student interactions have not been well studied. Here, we sought to develop and test a pilot survey of undergraduate students to determine how they got involved in research and in presenting at the Experimental Biology (EB) meeting, what they gained from the scientific and career development sessions at the meeting, and how the American Physiological Society (APS) can best support and engage undergraduate students. This survey was administered in 2014 and 2015 to undergraduate students who submitted physiology abstracts for and attended EB. More than 150 students responded (38% response rate). Respondents were demographically representative of undergraduate students majoring in life sciences in the United States. Most students (72%) became involved in research through a summer research program or college course. They attended a variety of EB sessions, including poster sessions and symposia, and found them useful. Undergraduate students interacted with established researchers at multiple venues. Students recommended that APS provide more research fellowships (25%) and keep in touch with students via both e-mail (46%) and social media (37%). Our results indicate that APS' EB undergraduate activities are valued by students and are effective in helping them have a positive scientific meeting experience. These results also guided the development of a more streamlined survey for use in future years. Copyright © 2017 the American Physiological Society.

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