14 research outputs found

    Next generation bioreactor with cyclic mechanical stretch on biomimetic lung tissue

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    Synergistic Effect of Elicitors in Enhancement of Ganoderic Acid Production: Optimization and Gene Expression Studies

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    Ganoderma lucidum is one of the most well-known fungi, and has many applications in medicine. Ganoderic acid is among the valuable secondary metabolites of Ganoderma lucidum, and responsible for the inhibition of the tumor cell growth and cancer treatment. Application of ganoderic acid has been limited because of low yields of its production from Ganoderma lucidum. The present study aims to investigate the synergistic effect of elicitors including methyl jasmonate and aspirin on the production of ganoderic acid derived from Ganoderma lucidum mushroom in a shaken flasks using response surface methodology. The results showed that the optimal dose of methyl jasmonate and asprin significantly impacts on the amount of ganoderic acid production as a response (p<0.05). The proposed model predicted the maximum ganoderic acid production as 0.085 mgml-1 in which the optimal concentrations obtained for methyl jasmonate and asprin were 250 mM and 4.4 mM, respectively. Also the influence of ganoderic acid production on the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and squalene synthase (two important metabolic pathway genes in ganoderic acid) was investigated, and the results showed that these genes’ expression has increased by 10 and 11 folds, respectively. 

    Administracja samorządowa i instytucje kultury w województwie podlaskim. Podstawy regionalnej polityki publicznej

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    The subject of the analysis in the article is the participation of the local government administration in running a cultural institution. The situation in the Podlaskie voivodship has been analyzed on a nationwide basis. The main problems focus on the principles and methods of financing cultural institutions by regional self-government and various ways of obtaining additional, extra-budgetary funding for their activities, especially from Ministry of Culture and National Heritage and the European Union. The author points to spatial, social, and financial diversification related to the access to cultural events and participation in them using the example of Podlaskie voivodship. He propounds greater professionalisation related to running cultural institutions at the level of the voivodship as well as conducting pro-development cultural policy by local government units. He also stresses the need for activating local and regional communities in connection with cultural events and participation in organizing them. Participation in culture at the local and regional level and prudent government policy in this area are the foundation for building a strong social and regional identity.Przedmiotem analizy w artykule jest udział administracji jednostek samorządu terytorialnego w prowadzeniu instytucji kultury. Na tle ogólnopolskim przeanalizowana została sytuacja w województwie podlaskim. Główne zagadnienia opracowania to zasady i metody finansowania instytucji kultury przez regionalny samorząd terytorialny oraz różne sposoby pozyskiwania przez instytucje kultury dodatkowego,  pozabudżetowego dofinansowania ich działalności, szczególnie ze środków pochodzących z budżetu Ministerstwa Kultury i Dziedzictwa Narodowego oraz Unii Europejskiej. Autor wskazuje na zróżnicowanie przestrzenne, społeczne i finansowe związane z dostępem do wydarzeń kulturalnych i uczestnictwem w nich na przykładzie województwa podlaskiego. Postuluje większą profesjonalizację zarządzania instytucjami kultury na szczeblu województwa oraz prowadzenie prorozwojowej polityki kulturalnej przez jednostki samorządu terytorialnego. Akcentuje również konieczność aktywizowania lokalnych i regionalnych społeczności w związku z wydarzeniami kulturalnymi i współuczestniczenia mieszkańców w ich organizowaniu. Uczestnictwo w kulturze na poziomie lokalnym i regionalnym oraz rozważna polityka władz w tym zakresie są podstawą budowania silnych więzi społecznych i tożsamości regionalnej mieszkańców

    An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials

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    Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ 12) and titanium dioxide nanoparticles (TiO 2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ 12 and TiO 2 NM-105 particles showed good linearity (R 2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ 12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO 2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO 2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials

    A Biomimetic, Copolymeric Membrane for Cell‐Stretch Experiments with Pulmonary Epithelial Cells at the Air‐Liquid Interface

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    Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε‐)caprolactone and gelatin with tunable properties, resembling the main characteristics of the alveolar basement membrane is introduced. The thin bioinspired membrane (≤5 μm) is stretchable (up to 25% linear strain) with appropriate surface wettability and porosity for culturing lung epithelial cells under air–liquid interface conditions. The unique biphasic concept of this membrane provides optimum characteristics for initial cell growth (phase I) and then switch to biomimetic properties for cyclic cell‐stretch experiments (phase II). It is showed that physiologic cyclic mechanical stretch improves formation of F‐actin cytoskeleton filaments and tight junctions while non‐physiologic over‐stretch induces cell apoptosis, activates inflammatory response (IL‐8), and impairs epithelial barrier integrity. It is also demonstrated that cyclic physiologic stretch can enhance the cellular uptake of nanoparticles. Since this membrane offers considerable advantages over currently used membranes, it may lead the way to more biomimetic in vitro models of the lung for translation of in vitro response studies into clinical outcome

    BeWell+: Multi-dimensional Wellbeing Monitoring with Community-guided User Feedback and Energy Optimization

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    Smartphone sensing and persuasive feedback design is enabling a new generation of wellbeing applications capable of automatically monitoring multiple aspects of physical and mental health. In this paper, we present BeWell+ the next generation of the BeWell smartphone health app, which continuously monitors user behavior along three distinct health dimensions, namely sleep, physical activity, and social interaction. BeWell promotes improved behavioral patterns via feedback rendered as an ambient display on the smartphone's wallpaper. With BeWell+, we introduce new wellbeing mechanisms to address challenges identified during the initial deployment of the BeWell app; specifically, (i) community adaptive wellbeing feedback, which automatically generalize to diverse user communities (e.g., elderly, young adults, children) by balancing the need to promote better behavior yet remains realistic to the user's goals; and, (ii) wellbeing adaptive energy allocation, which prioritizes monitoring fidelity and feedback responsiveness on specific health dimensions of wellbeing (e.g., social interaction) where the user needs most help. We evaluate the performance of these mechanisms as part of an initial deployment and user study that includes 27 people using BeWell+ over a 19 day field trial. Our findings show that not only can BeWell+ operate successfully on consumer-grade smartphones, but users understand feedback and respond by taking positive steps towards leading healthier lifestyles

    A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions

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    Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m2^{2}) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o^{-}) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung

    An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials.

    Get PDF
    Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation CV): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. a 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials
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