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Urine volumes and flows as functions of time after oral administration of placebo, furosemide 80 mg and tizolemide 100 mg to sixteen healthy male adults at 08.00 a.m. are described through mathematical models. Accumulated urine volumes after dosing, V, as functions of time, t, are accounted for by sigmoid functions and urine flows are described as dV/dt. No significant differences were found between the 24-hour urine volume mean values after furosemide (2457 ml) and tizolemide (2283 ml) and both were significantly higher than the corresponding mean value after placebo (1369 ml) (p < 0.001). Peak diuresis after dosing occurs about 1.5 hours for furosemide, 4 hours for tizolemide and 6 hours for placebo. Fourteen hours after dosing, urine volume amounts to 90% of the 24-hour urine volume after furosemide and to 76% after tizolemide, so that both substances may be regarded as diurnal diuretics.

Mesenchymal condensation is a prevalent morphogenetic transition that is essential in chondrogenesis. However, the current understanding of condensation mechanisms is limited. In vivo, progenitor cells directionally migrate from the surrounding loose mesenchyme towards regions of increasing matrix adherence (the condensation centers), which is accompanied by the upregulation of fibronectin. Here, we focused on the mechanisms of cell migration during mesenchymal cell condensation and the effects of matrix adherence. Dendrimer-based nanopatterns of the cell-adhesive peptide arginine-glycine-aspartic acid (RGD), which is present in fibronectin, were used to regulate substrate adhesion. We recorded collective and single-cell migration of mesenchymal stem cells, under chondrogenic induction, using live-cell imaging. Our results show that the cell migration mode of single cells depends on substrate adhesiveness, and that cell directionality controls cell condensation and the fusion of condensates. Inhibition experiments revealed that cell???cell interactions mediated by N-cadherin (also known as CDH2) are also pivotal for directional migration of cell condensates by maintaining cell???cell cohesion, thus suggesting a fine interplay between cell???matrix and cell???cell adhesions. Our results shed light on the role of cell interactions with a fibronectin-depositing matrix during chondrogenesis in vitro, with possible applications in regenerative medicine.

Osteosarcoma is one of the most common types of bone cancers among paediatric patients. Despite the advances made in surgery, chemo-, and radiotherapy, the mortality rate of metastatic osteosarcoma remains unchangeably high. The standard drug combination used to treat this bone cancer has remained the same for the last 20 years, and it produces many dangerous side effects. Through history, from ancient to modern times, nature has been a remarkable source of chemical diversity, used to alleviate human disease. The application of modern scientific technology to the study of natural products has identified many specific molecules with anti-cancer properties. This review describes the latest discovered anti-cancer compounds extracted from traditional medicinal plants, with a focus on osteosarcoma research, and on their cellular and molecular mechanisms of action. The presented compounds have proven to kill osteosarcoma cells by interfering with different pathways: apoptosis induction, stimulation of autophagy, generation of reactive oxygen species, etc. This wide variety of cellular targets confer natural products the potential to be used as chemotherapeutic drugs, and also the ability to act as sensitizers in drug combination treatments. The major hindrance for these molecules is low bioavailability. A problem that may be solved by chemical modification or nano-encapsulation.

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200–280 nm), -B (280–315 nm), and -A (315–400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85–0.90 times lower than control values at 7 and 14- days and 1.05–1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation., Junta de Andalucia PE-0395-2019, University of Granada B-CTS-450-UGR20 A.TEP.280.UGR18, Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-CTS-450-UGR20, European Regional Development Fund (ERDF) through the "Una manera de hacer Europa" program Junta de Andalucia P20-00200, Spanish Government PGC2018-101904-A-100

In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal Disorders. This is a reference list of recognized diseases in humans and their causal genes published to help clinician diagnosis and scientific research advances. Complementary to mammalian models, zebrafish has emerged as an interesting species to evaluate chemical treatments against these human skeletal disorders. Due to its versatility and the low cost of experiments, more than 80 models are currently available. In this article, we review the state-of-art of this "aquarium to bedside" approach describing the models according to the list provided by the Nosology Committee. With this, we intend to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians under the scope of the Nosology Committee. Yes

Dry eye syndrome is a complex and insidious pathology with a high level of prevalence among the human population and with a consequently high impact on quality of life and economic cost. Currently, its treatment is symptomatic, mainly based on the control of lubrication and inflammation, with significant limitations. Therefore, the latest research is focused on the development of new biological strategies, with the aim of regenerating affected tissues, or at least restricting the progression of the disease, reducing scar tissue, and maintaining corneal transparency. Therapies range from growth factors and cytokines to the use of different cell sources, in particular mesenchymal stem cells, due to their multipotentiality, trophic, and immunomodulatory properties. We will review the state of the art and the latest advances and results of these promising treatments in this pathology.

International audience; Novel nucleoside derivatives were developed using the strategy of “terminal N,N-dimethylation” to impart tertiary amines to a 1,2,4-triazole nucleoside. The obtained lead compounds displayed significantly improved anticancer activity with dual mechanisms of cell death via apoptosis and autophagy, offering a fresh perspective to searching for new anticancer candidates.

Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better health and well-being, new biomedicines, natural cosmeceuticals, environmental conservation, and sustainable energy sources. These societal needs stimulated the interest of researchers on the diverse and underexplored marine environments as promising and sustainable sources of biomolecules and biomass, and they are addressed by the emerging field of marine (blue) biotechnology. Blue biotechnology provides opportunities for a wide range of initiatives of commercial interest for the pharmaceutical, biomedical, cosmetic, nutraceutical, food, feed, agricultural, and related industries. This article synthesizes the essence, opportunities, responsibilities, and challenges encountered in marine biotechnology and outlines the attainment and valorization of directly derived or bio-inspired products from marine organisms. First, the concept of bioeconomy is introduced. Then, the diversity of marine bioresources including an overview of the most prominent marine organisms and their potential for biotechnological uses are described. This is followed by introducing methodologies for exploration of these resources and the main use case scenarios in energy, food and feed, agronomy, bioremediation and climate change, cosmeceuticals, bio-inspired materials, healthcare, and well-being sectors. The key aspects in the fields of legislation and funding are provided, with the emphasis on the importance of communication and stakeholder engagement at all levels of biotechnology development. Finally, vital overarching concepts, such as the quadruple helix and Responsible Research and Innovation principle are highlighted as important to follow within the marine biotechnology field. The authors of this review are collaborating under the European Commission-funded Cooperation in Science and Technology (COST) Action Ocean4Biotech – European transdisciplinary networking platform for marine biotechnology and focus the study on the European state of affairs., This publication is based upon work from COST Action CA18238 (Ocean4Biotech), supported by COST (European Cooperation in Science and Technology) program.AR, KK, and TR: the publication is part of a project that has received funding from the European Union Horizon 2020 Research and Innovation Programme under grant agreement no. 774499 – GoJelly project. AR and KK: this research was funded by the Slovenian Research Agency (research core funding P1-0245 and P1-0237). AR: this publication has been produced with financial assistance of the Interreg MED Programme, co-financed by the European Regional Development Fund (Project No. 7032, internal ref. 8MED20_4.1_SP_001) – B-Blue project. AB: acknowledges the support from the Research Council of Norway through the grant 267474 from the HAVBRUK2 program. MLC: acknowledges the Portuguese Foundation for Science and Technology (UIDB/04326/2020), the European Maritime and Fisheries Fund (MAR2020 OSTEOMAR/16-02-01-FMP-0057 and ALGASOLE/16.02.01-FMP-0058), the European Regional Development Fund (Atlantic Area BLUEHUMAN/EAPA/151/2016 and INTERREG V-A Spain-Portugal ALGARED+), and the European Commision (H2020-MSCA-ITN BIOMEDAQU/766347). MFC: wishes to acknowledge the funding from CEEC program supported by FCT/MCTES (CEECIND/02968/2017); ACTINODEEPSEA project (POCI-01-0145-FEDER-031045) co-financed by COMPETE 2020, Portugal 2020, ERDF and FCT; Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 through national funds provided by FCT and ERDF. MC: financial support from the Programme of the Institute of Oceanology, PAS (grant no. II.3) and National Science Centre in Poland (project number NCN 2016/21/B/NZ9/02304). MCu: acknowledges the funding from the Ministerio de Ciencia e Innovación of Spain (SAF2009-0839 and RTA 2015-00010-C03-02) and INTERREG-MAC2/1.1b/279 (AHIDAGRO). AD-M: acknowledge financial support from INTERREG-MAC/1.1b/042 (BIOTRANSFER2) and Agustín de Betancourt Programme (Cabildo de Tenerife and Universidad de La Laguna). AD: work has been supported by the ERDF Activity 1.1.1.2 “Post-doctoral Research Aid” of the Specific Aid Objective 1.1.1, Operational Programme “Growth and Employment” (No. 1.1.1.2/VIAA/1/16/048). RJF: funding for this research was provided under the Marine Research Programme 2014–2020, through the Marine Institute of Ireland under grant PBA/MB/16/01 “A National Marine Biodiscovery Laboratory of Ireland (NMBLI)” and through the Food Institutional Research Measure, administered by the Department of Agriculture, Food, and the Marine, Ireland under grant issue 17/F/260 (MaraBioActive). SG: this work was supported by the Applied Molecular Biosciences Unit-UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019). SG thanks financial support provided by FCT/MCTES through grant IF/00700/2014 and OceanTresaures project PTDC/QUIQUI/119116/2010. NID: wishes to acknowledge the funding from the Croatian Science Foundation Project CELLSTRESS (IP-2018-01-5840). MMa and TD: we wish to acknowledge funding from the General Secretariat for Research and Technology (GSRT) and the Hellenic Foundation for Research and Innovation (HFRI) under grant no. 239 (SPINAQUA project). AM-G: acknowledges the financial contribution from the project BYTHOS funded by the European Union’s Interreg V-A Italia-Malta Programme under project code C1-1.1-9. HM-M: financial support from National Science Centre in Poland 2016/21/B/NZ9/02304 and 2017/25/B/NZ9/00202. MMe: this work has been supported by the French Government, through the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-15-IDEX-01. MMe: thanks the Canceropôle Provence-Alpes-Côte d’Azur, and the Provence-Alpes-Côte d’Azur Region for the financial support provided to the MetaboCell project. DO: supported by the Doctorate Study program in Ecology and Environmental Sciences, Marine Research Institute, Klaipėda University, Lithuania. CR: we gratefully acknowledge the Research Council of Norway, the Møre and Romsdal County Council and Møreforsking AS for their financial contributions through the PROMAC (244244; www.promac.no), the Norwegian Seaweed Biorefinery Platform (294946; http://seaweedplatform.no/), and the Blå-Grønn (55031) projects. ER: this work benefited from financial support from the PACA Canceropôle, the National Cancer Institute, the PACA Regional Council and the French Government, managed by the National Research Agency as part of the Université Côte d’AzurJEDI Investissement d’Avenir project (ANR-15-IDEX-01). JS: work was supported by the Slovenian Research Agency (P4-0127 and J4-1771). IS: financial support from Ministry of Education, Youth and Sports of the Czech Republic (project CZ.02.1.01/0.0/0.0/17_048/0007323). XT: the tool “RRI Roadmap” was developed as part of the European Horizon 2020 project MARINA “Marine Knowledge Sharing Platform for Federating Responsible Research and Innovation Communities” under the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 710566 (2016–2019). OT: his contribution is carried out with the support of the Marine Institute and is funded under the Marine Research Programme by the Irish Government (Grant-Aid Agreement No. PBA/MB/16/01).

Made available in DSpace on 2021-06-26T04:31:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Objective: The aim of this paper is to present the results of a consensus meeting on the threshold property requirements for the clinical use of conventional glass-ionomer cements (GICs) for restorative indications. Methods: Twenty-one experts on GICs evaluated the results of tests on mechanical and optical properties of 18 different brands of restorative GICs: Bioglass R [B], Chemfil Rock [CR], Equia Forte [EF], Gold Label 2 [GL2], Gold Label 9 [GL9], Glass Ionomer Cement II [GI], Ionglass [IG], Ion Z [IZ], Ionomaster [IM], Ionofil Plus [IP], Ionostar Plus [IS], Ketac Molar Easymix [KM], Magic Glass [MG], Maxxion R [MA], Riva Self Cure [R], Vidrion R [V], Vitro Fil [VF] and Vitro Molar [VM]. All experiments were carried out by a team of researchers from Brazil and England following strict protocols, under the same laboratory conditions throughout, and maintaining data integrity. Results: There was consensus on: determining as primary properties of the material: compressive strength, microhardness, acid erosion and fluoride release, and as secondary properties: contrast ratio and translucency parameter, in order to rank the materials. Seven brands were below the thresholds for restorative indications: IZ, IM, IG, MA, VF, B and MG. Conclusions: Based on the primary properties adopted as being essential for restorative indications, the conventional restorative GICs that met the thresholds and could be considered suitable as long-term restorative materials were: EF, GI, GL9, KM, IP, GL2, IS, CR, V, VM and R. A decision-making process to select the best GIC must also include results from clinical trials. Clinical significance: This study provides a ranking of GICs that could be considered suitable as long-term restorative materials based on their main properties. Univ Sao Paulo, Dept Restorat Dent, Bauru Sch Dent, Alameda Dr Octavio Pinheiro Brisolla 9-75, BR-17012901 Bauru, SP, Brazil Univ Estadual Maringa, Dept Restorat Dent, Av Colombo 5790 Jd, BR-87020900 Maringa, Parana, Brazil Univ Fed Uberlandia, Dept Restorat Dent, Av Joao Naves Avila 2121, BR-38408100 Uberlandia, MG, Brazil Univ Sao Paulo, Sch Dent, Dept Orthodont & Pediat Dent, Av Prof Lineu Prestes 2227, BR-05508000 Butanta, SP, Brazil State Univ Sao Paulo, Inst Sci & Technol, Av Engn Francisco Jose Longo 777, BR-1224500 Sao Jose Dos Campos, Brazil Univ Catolica Cordoba, Obispo Trejo 323,X5000 IYG, Cordoba, Argentina Univ Western Australia, OHCWA, 512,17 Monash Ave, Nedlands, WA 6009, Australia Univ Zagreb, Sch Dent Med, Gunduliceva Ul 5, Zagreb 10000, Croatia Radboud Univ Nijmegen, Med Ctr, Dept Dent, Philips van Leydenlaan 25, NL-6525 EX Nijmegen, Netherlands Univ Estadual Campinas, Piracicaba Dent Sch, Av Limeira 901, BR-13414903 Piracicaba, Brazil Univ British Columbia, Vancouver, BC V6T 1Z4, Canada Hacettepe Univ, Dept Restorat Dent, TR-06800 Ankara, Turkey Univ Brasilia, BR-70910900 Brasilia, DF, Brazil Karadeniz Tek Univ, TR-61080 Trabzon, Turkey State Univ Sao Paulo, Aracatuba Sch Dent, Rua Jose Bonifacio 1193, BR-16015050 Aracatuba, Brazil Bluefield Ctr Biomat, Unit 34, 67-68 Hatton Garden, London EC1N 8JY, England Queen Mary Univ London, Mile End Rd, London E1 4NS, England State Univ Sao Paulo, Inst Sci & Technol, Av Engn Francisco Jose Longo 777, BR-1224500 Sao Jose Dos Campos, Brazil State Univ Sao Paulo, Aracatuba Sch Dent, Rua Jose Bonifacio 1193, BR-16015050 Aracatuba, Brazil FAPESP: 2018/01616-9 CNPq: 312060/2017-3

Objectives To investigate the pulpal repair potential of an experimental zirconium-oxide containing tricalcium-silicate cement, referred to as ‘TCS 50’. Materials and methods The effect of TCS 50 on viability, proliferation, migration, and odontoblastic differentiation of human dental pulp cells (HDPCs) was assessed using XTT assay, in-vitro wound healing assay and RT-PCR, respectively. Additionally, the pulp-capping potential was evaluated using a vital human tooth model. Statistical analysis was performed using non-parametric Kruskal-Wallis test and post-hoc test (Mann-Whitney U test). The tests were performed at a significance level of α = 0.05. Results The effect of TCS 50 towards HDPCs was dose dependent. Undiluted TCS 50 extract showed no immediate adverse impact on cell viability (p > .05); however, it significantly inhibited proliferation and migration of HDPCs (p < .05). A 25% diluted TCS 50 extract showed no significant effect on cell viability, proliferation or migration (p > .05), and it significantly enhanced odontoblastic differentiation of HDPCs (p < .05). In pulps capped with TCS 50 for both 2 and 4 weeks, H&E staining revealed a normal morphology of pulp tissue; mineralized foci with cellular components entrapped in the matrix were formed underneath the exposure site. Collagen I expression was weak within the matrix of mineralized foci, while the expression of nestin was positive for entrapped cellular components within the mineralized foci, indicating that the formed mineralized foci corresponded to an initial form of reparative dentin formation. Conclusion TCS 50 is capable of generating an early pulp-healing reaction and therefore could serve as a promising pulp-capping agent. ispartof: Materials Science & Engineering C-Materials For Biological Applications vol:116 ispartof: location:Netherlands status: Published online

WOS: 000467668800012 In the last decade, nerve tissue engineering has attracted much attention due to the incapability of self-regeneration. Nerve tissue regeneration is mainly based on scaffold induced nanofibrous structures using both bio and synthetic polymers. The produced nanofibrous scaffolds have to be similar to the natural extracellular matrix and should provide an appropriate environment for cells to attach onto. Nanofibrous scaffolds can support or regenerate cells of tissue. Electrospinning is an ideal method for producing the nanofibrous scaffolds. In this study, Bacterial cellulose (BC)/Poly (epsilon-caprolactone) (PCL) blend nanofibrous scaffolds were successfully prepared by electrospinning for nerve tissue induced repair. The produced nanofibrous scaffolds contain well defined interconnected nanofiber networks with hollow micro/nanobeads. Firstly, in-vitro biocompatibilities of nanofibrous scaffolds were tested with L2929 murine fibroblasts and improved cell adhesion and proliferation was observed with polymer blends compared with PCL only. The primary cell culture was performed with dorsal root ganglia (DRG) cells on nanofibrous samples and the samples were found suitable for enhancing neural growth and neurite outgrowth. Based on these results, the BC/PCL (50:50 wt.%) nanofibrous scaffolds exhibited nerve-like branching and are excellent candidate for potential biomimetic applications in nerve tissue engineering regeneration.

Made available in DSpace on 2018-11-29T19:30:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01. Added 1 bitstream(s) on 2021-07-15T15:20:55Z : No. of bitstreams: 1 S1678-77572018000100473.pdf: 1730795 bytes, checksum: 10c3efd0f5dc77d5cdc6c396a21b6d02 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) High levels of shrinkage stress caused by volumetric variations during the activation process are one of the main problems in the practical application of composite resins. Objective: The aim of this study is to reduce the shrinkage stress and minimize the effects caused by composite resin volumetric variation due to the photopolymerization. In this way, this work proposes a systematic study to determine the optimal dimming function to be applied to light curing processes. Material and Methods: The study was performed by applying mathematical techniques to the optimization of nonlinear objective functions. The effectiveness of the dimming function was evaluated by monitoring the polymerization shrinkage stress during the curing process of five brands/models of composites. This monitoring was performed on a universal testing machine using two steel bases coupled in the arms of the machine where the resin was inserted and polymerized. The quality of the composites cured by the proposed method was analyzed and compared with the conventional photoactivation method by experiments to determine their degree of conversion (DC). Absorbance measurements were performed using Fourier-transform infrared spectroscopy (FT-IR). A T-test was performed on DC results to compare the photoactivation techniques. We also used scanning electron microscopy (SEM) to analyze in-vitro the adhesion interface of the resin in human teeth. Results: Our results showed that the use of the optimal dimming function, named as exponential, resulted in the significant reduction of the shrinkage stress (similar to 36.88% +/- 6.56 when compared with the conventional method) without affecting the DC (t=0.86, p-value=0.44). The SEM analyses show that the proposed process can minimize or even eliminate adhesion failures between the tooth and the resin in dental restorations. Conclusion: The results from this study can promote the improvement of the composite resin light curing process by the minimization of polymerization shrinkage effects, given an operational standardization of the photoactivation process. Univ Estadual Paulista, Fac Ciencias Agron, Dept Bioproc & Biotecnol, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Botucatu, SP, Brazil Univ Estadual Paulista, Fac Ciencias, Lab Relaxacoes Anelast & Biomat, Bauru, SP, Brazil Inst Biomat Tribocorrosao & Nanomed Ramo Brasilei, Bauru, SP, Brazil Univ Estadual Paulista, Fac Ciencias Agron, Dept Bioproc & Biotecnol, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Botucatu, SP, Brazil Univ Estadual Paulista, Fac Ciencias, Lab Relaxacoes Anelast & Biomat, Bauru, SP, Brazil FAPESP: 2015/02136-2

The response to the HBV vaccine in HIV-infected patients is deficient. Our aim was to analyze whether a suppressive combined antiretroviral treatment (cART) containing maraviroc (MVC-cART) was associated with a better response to HBV vaccine. Fifty-seven patients on suppressor cART were administered the HBV vaccine. The final response, the early response, and the maintenance of the response were assessed. An anti-HBs titer of >10 mIU/ml was considered a positive response. A subgroup of subjects was simultaneously vaccinated against hepatitis A virus (HAV). Lineal regression analyses were performed to determine demographic, clinical, and immunological factors associated with the anti-HBs titer. Vaccine response was achieved in 90% of the subjects. After 1 year, 81% maintained protective titers. Only simultaneous HAV vaccination was independently associated with the magnitude of the response in anti-HBs titers, with a P value of 0.045 and a regression coefficient (B) [95% confident interval (CI)] of 236 [5 to 468]. In subjects ≤50 years old (n = 42), MVC-cART was independently associated with the magnitude of the response (P = 0.009; B [95% CI], 297 [79 to 516]) together with previous vaccination and simultaneous HAV vaccination. High rates of HBV vaccine response can be achieved by revaccination, simultaneous HAV vaccination, and administration of cARTs including MVC. MVC may be considered for future vaccination protocols in patients on suppressive cART., This study was funded by an investigator-initiated research grant from ViiV Healthcare S.L. (grant number 205644) and by grants from the Fondo de Investigación Sanitaria (FIS; PI14/01693; PI16/01863), cofunded by Fondos Europeos para el Desarrollo Regional (FEDER) and the Junta de Andalucía, Consejería de Economía, Innovación, Ciencia y Empleo (Proyecto de Investigación de Excelencia; CTS2593). The Spanish AIDS Research Network of Excellence also supported this study (RD16/0025/0019). E.R.-M. and Y.M.P. were supported by the Fondo de Investigación Sanitaria through the ‘Miguel Servet’ programs (CPII014/00025 and CPII13/00037, respectively). Y.M.P. was supported by the Consejería de Salud y Bienestar Social of Junta de Andalucía through the ‘Nicolás Monardes’ program (C-0010/13). L.T.-D. was supported by Instituto de Salud Carlos III (PFIS program; FI00/00431).

International audience; Metastasis is the cause of most (>90%) cancer deaths and currently lacks effective treatments. Approaches to understanding the biological process, unraveling the most effective molecular target(s), and implementing nanotechnology to increase the therapeutic index are expected to facilitate cancer therapy against metastasis. Here, we demonstrate the potential advantages of bringing these three approaches together through the rational design of a small interfering RNA (siRNA) that targets p70 S6K in cancer stem cells (CSCs) in combination with den-drimer nanotechnology-based siRNA delivery. Our results demonstrated that the generation 6 (G 6) poly(amidoamine) dendrimer can be used as a nanovector to effectively deliver p70 S6K siRNA by forming uniform dendriplex nanoparticles that protect the siRNA from degradation. These nanoparticles were able to significantly knock down p70 S6K in ovarian CSCs, leading to a marked reduction in CSC proliferation and expansion without obvious toxicity toward normal ovarian surface epithelial cells. Furthermore, treatment with the p70 S6K siRNA/G 6 dendriplexes substantially decreased mesothelial interaction, migration and invasion of CSCs in vitro, as well as tumor growth and metastasis in vivo. Collectively, these results suggest that p70 S6K constitutes a promising therapeutic target, and the use of siRNA in combination with nanotech-nology-based delivery may constitute a new approach for molecularly targeted cancer therapy to treat metastasis.

International audience; Small interfering RNA (siRNA) therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with cova-lent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types in vitro and in vivo, including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired structurally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self-assembling amphiphilic dendrimers to construct supramo-lecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great promise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.

National audience

Made available in DSpace on 2018-12-11T16:46:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-04-01 Objectives To evaluate the effect of restoration design (‘2.5-mm deep endocrown’, ‘5-mm deep endocrown’ or ‘5-mm deep post&crown’) and CAD/CAM material type (composite or lithium disilicate glass-ceramic) on the load-to-failure of endodontically treated premolars in absence of any ferrule. Methods The crowns of 48 single-rooted premolars were cut and the roots were endodontically treated. Teeth were randomly divided into six groups (n = 8); teeth in each group were restored using one of the two tested materials with standardized CAD/CAM fabricated endocrowns (with either 2.5-mm or 5-mm deep intra-radicular extension) or conventional crowns (5-mm deep post&crown). After cementation using luting composite, the specimens were immersed in distilled water and subjected to 1,200,000 chewing cycles with a load of 50 N applied parallel to the long axis of the tooth (0°). After cyclic loading, a compressive load was applied at 45° to the tooth's long axis using a universal testing machine until failure. Load-to-failure was recorded (N) and the specimens were examined under a stereomicroscope with 3.5x magnification to determine the mode of failure. Results All specimens survived the 1,200,000 chewing cycles. A significant interaction between restoration design and CAD/CAM material was found using two-way ANOVA. In the ‘2.5-mm deep endocrown’ groups, the composite achieved a significantly higher load-to-failure than the lithium disilicate glass-ceramic, while no differences between materials were found in the ‘5-mm deep endocrown’ and ‘5-mm deep post&crown’ groups. More unfavorable failures (root fractures) were observed for higher load-to-failure values. Conclusions Only following a ‘2.5-mm deep endocrown’ design, composite appeared more favorable than lithium disilicate glass-ceramic as crown material; this may be explained by their difference in elastic modulus. Clinical significance Shallow endocrown preparations on premolars present less surface for adhesive luting and a difference in crown material becomes apparent in terms of load-to-failure. The use of a more flexible composite crown material appeared then a better option. KU Leuven (University of Leuven) Department of Oral Health Sciences BIOMAT & University Hospitals Leuven (UZ Leuven), Dentistry Federal University of Santa Catarina (UFSC) Department of Operative Dentistry Sao Paulo State University (UNESP) School of Dentistry Department of Restorative Dentistry Sao Paulo State University (UNESP) School of Dentistry Department of Restorative Dentistry

Sulfapyridine (SPy) is a sulfonamide antibiotic largely employed as veterinary drugs for prophylactic and therapeutic purposes. Therefore, its spread in the food products has to be restricted. Herein, we report the synthesis and characterization of a novel electrochemical biosensor based on gold microelectrodes modified with a new structure of magnetic nanoparticles (MNPs) coated with poly(pyrrole-co-pyrrole-2-carboxylic acid) (Py/Py-COOH) for high efficient detection of SPy. This analyte was quantified through a competitive detection procedure with 5-[4-(amino)phenylsulfonamide]-5-oxopentanoic acid-BSA (SA2-BSA) antigens toward polyclonal antibody (Ab-155). Initially, gold working electrodes (WEs) of integrated biomicro electro-mechanical system (BioMEMS) were functionalized by Ppy-COOH/MNPs, using a chronoamperometric (CA) electrodeposition. Afterward, SA2-BSA was covalently bonded to Py/Py-COOH/MNP modified gold WEs through amide bonding. The competitive detection of the analyte was made by a mixture of a fixed concentration of Ab-155 and decreasing concentrations of SPy from 50µgL-1 to 2ngL-1. Atomic Force Microscopy characterization was performed in order to ensure Ppy-COOH/MNPs electrodeposition on the microelectrode surfaces. Electrochemical measurements of SPy detection were carried out using electrochemical impedance spectroscopy (EIS). This biosensor was found to be highly sensitive and specific for SPy, with a limit of detection of 0.4ngL-1. This technique was exploited to detect SPy in honey samples by using the standard addition method. The measurements were highly reproducible for detection and interferences namely, sulfadiazine (SDz), sulfathiazole (STz) and sulfamerazine (SMz). Taking these advantages of sensitivity, specificity, and low cost, our system provides a new horizon for development of advanced immunoassays in industrial food control.

International audience; Synthetic glycopolypeptides are versatile glycopolymers used to conceive bioinspired nanoassemblies. In this work, novel amphiphilic glycopolypeptides were designed to incorporate lactose or galactan in order to prepare polymeric nanoassemblies with sizes below 50 nm. The bioactivity of the two different outer surface sugar units was evaluated by defining glycan relative binding affinities to human galectins 1 and 3. A specific multivalent effect was found only for polymeric nanoparticles displaying galactan with a significant increase of the binding activity as compared to free glycan in solution. Such synthetic designs present great potential as therapeutic tools to address galectin related pathologies.

Pulse-labelling of trees with stable or radioactive carbon (C) isotopes offers the unique opportunity to trace the fate of labelled CO(2) into the tree and its release to the soil and the atmosphere. Thus, pulse-labelling enables the quantification of C partitioning in forests and the assessment of the role of partitioning in tree growth, resource acquisition and C sequestration. However, this is associated with challenges as regards the choice of a tracer, the methods of tracing labelled C in tree and soil compartments and the quantitative analysis of C dynamics. Based on data from 47 studies, the rate of transfer differs between broadleaved and coniferous species and decreases as temperature and soil water content decrease. Labelled C is rapidly transferred belowground-within a few days or less-and this transfer is slowed down by drought. Half-lives of labelled C in phloem sap (transfer pool) and in mature leaves (source organs) are short, while those of sink organs (growing tissues, seasonal storage) are longer. (13)C measurements in respiratory efflux at high temporal resolution provide the best estimate of the mean residence times of C in respiratory substrate pools, and the best basis for compartmental modelling. Seasonal C dynamics and allocation patterns indicate that sink strength variations are important drivers for C fluxes. We propose a conceptual model for temperate and boreal trees, which considers the use of recently assimilated C versus stored C. We recommend best practices for designing and analysing pulse-labelling experiments, and identify several topics which we consider of prime importance for future research on C allocation in trees: (i) whole-tree C source-sink relations, (ii) C allocation to secondary metabolism, (iii) responses to environmental change, (iv) effects of seasonality versus phenology in and across biomes, and (v) carbon-nitrogen interactions. Substantial progress is expected from emerging technologies, but the largest challenge remains to carry out in situ whole-tree labelling experiments on mature trees to improve our understanding of the environmental and physiological controls on C allocation.

International audience; Gelatin was chemically cross-linked with lactose in order to analyze the effect of this reaction in the antioxidant capacity of gelatin films. Since phenolic compounds are formed during cross-linking, the antioxidant activity of gelatin films was assessed. Although these cross-linking films showed certain antioxidant capacity, the incorporation of tetrahydrocurcumin (THC) into the films forming solutions greatly increased the antioxidant capacity of gelatin films. Total phenolic content, expressed as mg gallic acid equivalent (GAE), increased from 14 to 43 mg GAE/L. Furthermore, free radical scavenging capacity showed a three-fold increase, as shown by inhibition values. The changes observed were related to the differences found in the film surface, such as lower gloss and higher roughness.

WOS: 000183285100006, PubMed ID: 12797423, The aim of this study was to determine water sorption, solubility and dimensional stability of injection and compression-molded polymethyl methacrylate based denture base polymer that was reinforced with various concentrations and lengths of E-glass fibers. For water sorption and solubility, 20 test groups with different fiber contents and lengths of fibers were prepared. Test specimens without fibers were used as a control. The water sorption and solubility was measured after 90 days water storage. For dimensional stability, rhombic test specimens were prepared and the dimensional changes were measured after processing, drying and storing in water for 4 days and 30 days and were compared with those on the brass model. The water sorption and solubility of injection-molded denture base polymer was lower compared to compression-molded specimens (p 0.05).

The performance of a custom atomic force microscope for grazing-incidence X-ray experiments on hydrated soft and biological samples is presented., A fast atomic force microscope (AFM) has been developed that can be installed as a sample holder for grazing-incidence X-ray experiments at solid/gas or solid/liquid interfaces. It allows a wide range of possible investigations, including soft and biological samples under physiological conditions (hydrated specimens). The structural information obtained using the X-rays is combined with the data gathered with the AFM (morphology and mechanical properties), providing a unique characterization of the specimen and its dynamics in situ during an experiment. In this work, lipid monolayers and bilayers in air or liquid environment have been investigated by means of AFM, both with imaging and force spectroscopy, and X-ray reflectivity. In addition, this combination allows the radiation damage induced by the beam on the sample to be studied, as has been observed on DOPC and DPPC supported lipid bilayers under physiological conditions.

Magnetic actuation of microscopic devices in a liquid environment has been achieved in various ways, which can be grouped into rolling, propelling and swimming. Previous actuators were designed with a focus on one particular type of magnetic actuation. We have shown earlier that efficient magnetic propellers can be selected from randomly shaped magnetic nanostructures synthesized in solution. Here we show that these synthesized nanostructures can be used for all three types of magnetic actuation. Whereas it might not be surprising that single structures can roll in addition to propelling, swimming is unexpectedly also observed using the same material. In this case, however, the magnetically guided self-assembly of several individual particles into chain-like structures is necessary to obtain swimmers, since individual rigid nanostructures cannot swim. Interestingly, the direction of the swimming motion is not necessarily parallel to the long axis of the chain-like assembly, a finding that had been theoretically expected but experimentally not observed so far. Our findings show that the range of structures that can be effectively actuated by external magnetic fields is much broader than assumed until now. This could open up new opportunities for the design of magnetically actuated devices.

Infections and their consequences are a considerable problem in orthopaedic surgery. Despite intravenous prophylactic antibiotic administration, infection rates can reach in some occasions more than 1%. Indeed, the concentration in bone tissues is very low with the majority of antibiotics. Because high local dose can be obtained, the local release of gentamicin from acrylic bone cements has been shown to be efficient in preventing infections. However, for surgical procedures other than cemented prostheses no other local antibiotic releasing device is clinically available. The purpose of this study was to validate the concept of a gentamicin loaded bone substitute. About 125 mg of gentamicin were introduced into a HAP/TCP bone substitute for prophylactic purpose, to enhance the efficiency of systemic antibiotic treatments. The release rate of gentamicin from the bone substitute was investigated in vitro, in 0.9% sodium chloride solution. The rate appeared to be related to the bone substitute volume. All the gentamicin was released in less than 48 h. This release rate corresponds to the recommendations for the prophylactic use of antibiotics: the duration of the treatment should be less than 48 h, not to select antibiotic-resistant bacterial strains.

This work is a quantitative study of the conditions required for a long-term passivation of the interface silicon-alkyl monolayers prepared by thermal hydrosilyation of neat 1-alkenes on well-defined H-Si(111) surfaces. We present electrochemical capacitance measurements (C-U) in combination with ex situ atomic force microscopy (AFM) observations and X-ray photoelectron spectroscopy (XPS) measurements. Capacitance measurements as a function of the reaction time and XPS data reveal close correlations between the chemical composition at the interface and its electronic properties. A very low density of states is found if suboxide formation is carefully prevented. The monitoring of C-U plots and AFM imaging upon exposure of the sample in diverse conditions indicate that the initial electronic properties and structure of the interface are long-lasting only when the monolayer surface coverage is theta0.42. A model demonstrates that this threshold value corresponds to a monolayer with intermolecular channels narrower than approximately 2.82 A, which is equal to the diameter of a water molecule. Water exclusion from the monolayer promotes long-term passivation of the silicon surface against oxidation in air and water as well as perfect corrosion inhibition in 20% NH(4)F. We provide two criteria to assess when a sample is optimized: The first one is an effective dielectric constant2.5, and the second one is a very characteristic energy diagram at open circuit potential.

WOS: 000185967800010, PubMed ID: 14564293, Statement of problem. Fiber-reinforcement has been used to overcome the mechanical limitations of denture base polymers. One major difficulty in the use of fiber reinforcement has been the addition of fibers during conventional processing methods. Purpose. This study evaluated the effect of various lengths and concentrations of chopped E-glass fiber-reinforcement on the transverse strength, modulus of elasticity, and impact strength of injection and compression-molded polymethyl methacrylate based denture base polymer. Material and methods. Test specimens (n = 10) of 4-, 6-, and 8-mm fiber length and 1%, 3%, and 5% weight fiber concentrations were prepared with either an injection or a compression-molded processing method. Denture base polymer specimens without any fiber reinforcement were used as control for both processing methods. Transverse strength test specimens (65 x 10 x 2.5 mm) were stored in water bath at 37degreesC for 2 weeks. The transverse strength (MPa) and modulus of elasticity (GPa) was measured with the 3-point bending test. Impact strength (kJ/m(2)) test specimens (60 x 7.5 x 4 mm) were tested with the Charpy-type pendulum impact test setup. The data were analyzed with multifactorial analysis of variance and Tukey post hoc tests (alpha = .05). Results. Injection-molded fiber-reinforced groups showed significantly higher transversal strength, elastic modulus, and impact strength compared with compression-molded groups (P < .001). In the injection-molded groups, fiber concentration increased all mechanical properties tested (P < .05), but fiber length only increased transverse strength and modulus of elasticity (P < .05). In the compression molded groups, fiber concentration affected modulus of elasticity and impact strength significantly (P < .05), but fiber length did not show any significant effect on the mechanical properties tested (P > .05). Conclusion. The transverse strength, elastic modulus and impact strength of injection-molded denture base polymer increased significantly with the use of chopped E-glass fibers, whereas the effect was not significant with the compression-molded polymer.