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Objective: Aspirated foreign bodies (FB) are potentially life-threatening conditions which can be challenging to diagnose in children. The previous similar study from our hospital, published in 2014, created a guideline suggesting when to proceed to laryngobronchoscopy (LB) in suspected FB aspiration with over 99 % sensitivity. The grading system included the presence or absence of acute history, positive examination, and/or radiological findings, including witnessed choking, dysphonia, stridor, wheezing, or reduced air entry on examination or abnormal radiological findings. The current study reviewed a further 10 years and 5 months of data to re-evaluate the ongoing diagnostic usefulness of the three positive findings in children with suspicion of aspirated FB., Methods: We undertook a retrospective review of all LB performed at our institution for suspected acute FB aspiration from August 2013 to January 2023. We analysed patient characteristics, clinical examination, radiological findings, and outcomes., Results: We found a total of 100 children under the age of 16 years who underwent LB for suspected FB aspiration. The mean age of our study population was 2.6 years. The population demographics were similar to the results from the previous study from our institution, with Māori and Pasifika children having the highest probability of finding a FB on LB. Male children presenting for suspected FB aspiration are 1.39 times more likely than female children to have a foreign body at LB (p = 0.04). Overall, having two or more positive findings had a sensitivity of 100 %. History or examination alone are more sensitive (both 95.6 %) but less specific (12.5 % and 31.3 %, respectively). Abnormal radiology alone was more specific (75.0) but less sensitive (77.9 %). The most common site of FB was the right bronchial tree (45.6 %), followed by the left (39.7 %). 95 % of FB were organic, and 54 % were nuts. The negative bronchoscopy rate was 32 %., Conclusion: Two or more positive indicators in history, examination and radiological findings continue to be highly sensitive predictors for the presence of an aspirated foreign body in our paediatric population. We recommend a future large-scale multicentre study to confirm how applicable these findings would be to a broader cohort of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

This study presents the synthesis and characterization of hexadecyl-modified SiO 2 (HD-SiO 2 ) nanoparticles and their application in the fabrication of a multilayered elastomer hybrid sheet to enhance water resistance in implantable biomedical devices. The surface modification of SiO 2 nanoparticles was confirmed via FT-IR and TGA analyses, showing the successful grafting of hydrophobic hexadecyl groups. FE-SEM and DLS analyses revealed spherical HD-SiO 2 nanoparticles with an average size of 360 nm. A multilayered elastomer hybrid sheet, consisting of a PDMS-based circuit-protecting body, a water resistance layer of HD-SiO 2 , a planarization layer, and a biocompatible layer of polydopamine, was fabricated and characterized. The water resistance layer exhibited superhydrophobic properties, with a water contact angle of 154.7° and a 27% reduction in water vapor transmission rate (WVTR) compared to the circuit-protecting body alone. The device packaged with both the circuit-protecting body and water resistance layer demonstrated a tenfold increase in operational lifespan in water medium compared to the device without the water resistance layer. Cytotoxicity and cell proliferation tests on human dermal fibroblast cells (HDFn) confirmed the biocompatibility of the multilayered sheet, with no significant cytotoxicity observed over 48 h.

We developed a tailored 3D Agarose-well system integrated with reconstructed human skin equivalents to enhance skin penetration assessments. This system addresses common limitations in traditional trans-well reconstructions, such as dermal layer contraction and limited lateral diffusion, by entangling collagen fibrils within the Agarose-well. We evaluated the penetration behavior of three peptides, with and without skin-penetrating peptide (SPP) sequences, alongside adenosine, a known anti-wrinkle agent. Despite a SPP having a molecular weight approximately four times greater than that of adenosine, its kinetic constant was similar, with values of about 39 and 34, respectively. Moreover, this living skin equivalent system not only allowed for the evaluation of adenosine penetration, but also demonstrated its biological effects, with adenosine significantly enhancing procollagen synthesis by approximately 23% compared to the control. Overall, this novel strategy holds the potential for tailoring 3D Agarose-wells and advancing high-performance gel development, making it a promising approach for applications in tissue engineering, medical science, regenerative medicine, and cosmetics.

The integration of nanoparticles (NPs) into molecular self-assemblies has been extensively studied with the aim of building well-defined, ordered structures which exhibit advanced properties and performances. This study demonstrates a novel strategy for the preparation of a spike-like self-assembly designed to enhance UV blocking. Poly(2-hydroxyethyl aspartamide) (PHEA) substituted with octadecyl chains and menthyl anthranilate (C 18 -M-PHEA) was successfully synthesized by varying the number of grafted groups to control their morphology and UV absorption. The in situ incorporation of polymerized rod-like TiO 2 within the C 18 -M-PHEA self-aggregates generated spike-like self-assemblies (TiO 2 @C 18 -M-PHEA) with a chestnut burr structure in aqueous solution. The results showed that the spike-like self-assemblies integrated with TiO 2 NPs exhibited a nine-fold increase in UV protection by simultaneous UV absorption and scattering compared with the pure TiO 2 NPs formed via a bulk mixing process. This work provides a novel method for UV protection using self-assembling poly(amino acid)s derivatives integrated with functional nanoparticles to tune their morphology and organization.

Multi-layered hydrogels consisting of bi- or tri-layers with different swelling ratios are designed to soft hydrogel actuators by self-folding. The successful use of multi-layered hydrogels in this application greatly relies on the precise design and fabrication of the curvature of self-folding. In general, however, the self-folding often results in an undesired mismatch with the expecting value. To address this issue, this study introduces an interfacial layer formed between each layered hydrogel, and this layer is evaluated to enhance the design and fabrication precision. By considering the interfacial layer, which forms through diffusion, as an additional layer in the multi-layered hydrogel, the degree of mismatch in the self-folding is significantly reduced. Experimental results show that as the thickness of the interfacial layer increases, the multi-layered hydrogel exhibits a 3.5-fold increase in its radius of curvature during the self-folding. In addition, the diffusion layer is crucial for creating robust systems by preventing the separation of layers in the muti-layered hydrogel during actuation, thereby ensuring the integrity of the system in operation. This new strategy for designing multi-layered hydrogels including an interfacial layer would greatly serve to fabricate precise and robust soft hydrogel actuators.

Neural interfaces play a major role in modulating neural signals for therapeutic purposes. To meet the demand of conformable neural interfaces for developing bioelectronic medicine, recent studies have focused on the performance of electrical neurostimulators employing soft conductors such as conducting polymers and electronic or ionic conductive hydrogels. However, faradaic charge injection at the interface of the electrode and nerve tissue causes irreversible gas evolution, oxidation of electrodes, and reduction of biological ions, thus causing undesired tissue damage and electrode degradation. Here we report a conformable neural interface engineering based on multicross-linked membrane-ionogel assembly (termed McMiA), which enables nonfaradaic neurostimulation without irreversible charge transfer reaction. The McMiA consists of a genipin-cross-linked biopolymeric ionogel coupled with a dopamine-cross-linked graphene oxide membrane to prevent ion exchange between biological and synthetic McMiA ions and to function as a bioadhesive forming covalent bonds with the target tissues. In addition, the demonstration of bioelectronic medicine via the McMiA-based neurostimulation of sciatic nerves shows the enhanced clinical utility in treating the overactive bladder syndrome. As the McMiA-based neural interface is soft, robust for bioadhesion, and stable in a physiological environment, it can offer significant advancement in biocompatibility and long-term operability for neural interface engineering.

There have been several trials to develop the bioactuator using skeletal muscle cells for controllable biobybird robot. However, due to the weak contraction force of muscle cells, the muscle cells could not be used for practical applications such as biorobotic hand for carrying objects, and actuator of biohybrid robot for toxicity test and drug screening. Based on reported hyaluronic acid-modified gold nanoparticles (HA@GNPs)-embedded muscle bundle on PDMS substrate, in this study for augmented actuation, we developed the electroactive nano-biohybrid actuator composed of the HA@GNP-embedded muscle bundle and molybdenum disulfide nanosheet (MoS 2 NS)-modified electrode to enhance the motion performance. The MoS 2 NS-modified Au-coated polyimide (PI) electrode to be worked in mild pH condition for viable muscle cell was utilized as supporting- and motion enhancing- substrate since it was electrochemically active, which caused the movement of flexible PI electrode. The motion performance of this electroactive nano-biohybrid actuator by electrical stimulation was increased about 3.18 times compared with that of only HA@GNPs embedded-muscle bundle on bare PI substrate. The proposed electroactive nano-biohybrid actuator can be applied to the biorobotic hand and biohybrid robot., (© 2022. The Author(s).)

The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular-based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3-L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis. Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3-L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics-based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti-lipogenic agents., (© 2021 Wiley-VCH GmbH.)

Although there are various pre-existing technologies for engineering vasculatures, multiscale modeling of the architecture of human vasculature at a capillary scale remains a challenge. In this study, a novel technology is developed for the production of a functional, multiscale microvasculature comprising of endothelialized channels and tissue-specific capillary networks. Perfusable, endothelialized channels are bioprinted, after which angiogenic sprouts are grown into user-designed capillary networks. The induction of branched and liver-lobule-like capillary networks confirm that the technology can produce various types of tissue-specific multiscale microvasculatures. Further, the channels and capillaries are deemed to be functional when evaluated in vitro. An ex vivo assay demonstrates that the microvasculature can induce neovessel ingrowth, integrate with host vessels, and facilitate blood flow. Remarkably, blood flows through the implanted capillary network without any change in its morphology. Finally, the technology is applied to produce a vascularized liver tissue; it significantly improves its hepatic function. It is believed that this new technology will create new possibilities in the development of highly vascularized and functional tissues/organs on a clinically relevant scale., (© 2021 Wiley-VCH GmbH.)

To use implantable biomedical devices such as electrocardiograms and neurostimulators in the human body, it is necessary to package them with biocompatible materials that protect the internal electronic circuits from the body's internal electrolytes and moisture without causing foreign body reactions. Herein, we describe a hydrogel surface-modified polyurethane copolymer film with concurrent water permeation resistance and biocompatibility properties for application to an implantable biomedical device. To achieve this, hydrophobic polyurethane copolymers comprising hydrogenated poly(ethylene-co-butylene) (HPEB) and aliphatic poly(carbonate) (PC) were synthesized and their hydrophobicity degree and mechanical properties were adjusted by controlling the copolymer composition ratio. When 10 wt% PC was introduced, the polyurethane copolymer exhibited hydrophobicity and water permeation resistance similar to those of HPEB; however, with improved mechanical properties. Subsequently, a hydrophilic poly(vinyl pyrrolidone) (PVP) hydrogel layer was formed on the surface of the polyurethane copolymer film by Fenton reaction using an initiator and crosslinking agent and the effect of the initiator and crosslinking agent immobilization time, PVP concentration and crosslinking agent concentration on the hydrogel properties were investigated. Finally, MTT assay showed that the hydrogel surface-modified polyurethane copolymer film displays excellent biocompatibility.

The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells., (© 2021 Wiley Periodicals LLC.)

The hydrogels are widely used in various applications, and their successful uses depend on controlling the mechanical properties. In this study, we present an advanced strategy to develop hydrogel actuator designed to stimulate live cell clusters by self-folding. The hydrogel actuator consisting of two layers with different expansion ratios were fabricated to have various curvatures in self-folding. The expansion ratio of the hydrogel tuned with the molecular weight and concentration of gel-forming polymers, and temperature-sensitive molecules in a controlled manner. As a result, the hydrogel actuator could stimulate live cell clusters by compression and tension repeatedly, in response to temperature. The cell clusters were compressed in the 0.7-fold decreases of the radius of curvature with 1.0 mm in room temperature, as compared to that of 1.4 mm in 37 °C. Interestingly, the vascular endothelial growth factor (VEGF) and insulin-like growth factor-binding protein-2 (IGFBP-2) in MCF-7 tumor cells exposed by mechanical stimulation was expressed more than in those without stimulation. Overall, this new strategy to prepare the active and soft hydrogel actuator would be actively used in tissue engineering, drug delivery, and micro-scale actuators.

Hydrogels incorporated with hydrophobic motifs have received considerable attention to recapitulate the cellular microenvironments, specifically for the bio-mineralization of a 3D matrix. Introduction of hydrophobic molecules into a hydrogel often results in irregular arrangement of the motifs, and further phase separation of hydrophobic domains, but limited efforts have been made to resolve this challenge in developing the hydrophobically-modified hydrogel. Therefore, this study presents an advanced integrative strategy to incorporate hydrophobic domains regularly in a hydrogel using self-assembled domains formed with polymer cross-linkers, building blocks of a hydrogel. Self-assemblies formed by polymer cross-linkers were examined as micro-domains to incorporate hydrophobic motifs in a hydrogel. The self-assembled structures in a pre-gelled solution were confirmed with the fluorescence analysis and the hydrophobicity of a hydrogel could be tuned by incorporating the hydrophobic chains in a controlled manner. Overall, the results of this study would greatly serve to tuning performance of a wide array of hydrophobically-modified hydrogels in drug delivery, cell therapies and tissue engineering.

Although several biomarkers can be used to distinguish cholangiocarcinoma (CCA) from healthy controls, differentiating the disease from benign biliary disease (BBD) or pancreatic cancer (PC) is a challenge. CCA biomarkers are associated with low specificity or have not been validated in relation to the biological effects of CCA. In this study, we quantitatively analyzed 15 biliary bile acids in CCA (n = 30), BBD (n = 57) and PC (n = 17) patients and discovered glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) as specific CCA biomarkers. Firstly, we showed that the average concentration of total biliary bile acids in CCA patients was quantitatively less than in other patient groups. In addition, the average composition ratio of primary bile acids and conjugated bile acids in CCA patients was the highest in all patient groups. The average composition ratio of GCA (35.6%) in CCA patients was significantly higher than in other patient groups. Conversely, the average composition ratio of TCDCA (13.8%) in CCA patients was significantly lower in all patient groups. To verify the biological effects of GCA and TCDCA, we analyzed the gene expression of bile acid receptors associated with the development of CCA in a CCA cell line. The gene expression of transmembrane G protein coupled receptor (TGR5) and sphingosine 1-phosphate receptor 2 (S1PR2) in CCA cells treated with GCA was 8.6-fold and 3.4-fold higher compared with control (untreated with bile acids), respectively. Gene expression of TGR5 and S1PR2 in TCDCA-treated cells was not significantly different from the control. Taken together, our study identified GCA and TCDCA as phenotype-specific biomarkers for CCA.

Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers. FACS and MR molecular imaging revealed that the Her2/neu overexpressing cell line showed a stronger contrast enhancement than the Her2/neu non-expressing cell lines, and the signal intensity of in vivo MR imaging decreased as the concentration of Herceptin increased. This strategy of encapsulating SPIONs with PLGA will be highly useful in functionalizing magnetic nanoparticles and improving the diagnostic and therapeutic efficacy of a wide array of cancer treatments.

Recently, polymeric micelles self-assembled from amphiphilic polymers have been studied for various industrial and biomedical applications. This nanoparticle self-assembly typically occurs in a solvent-exchange process. In this process, the quality of the resulting particles is uncontrollably mediated by polymeric solubility and mixing conditions. Here, we hypothesized that improving the solubility of an amphiphilic polymer in an organic solvent via chemical modification while controlling the mixing rate of organic and aqueous phases would enhance control over particle morphology and size. We examined this hypothesis by synthesizing a poly(2-hydroxyethyl)aspartamide (PHEA) grafted with controlled numbers of octadecyl (C 18 ) chains and oligovaline groups (termed "oligovaline-PHEA-C 18 "). The mixing rate of DMF and water was controlled either by microfluidic mixing of laminar DMF and water flows or through turbulent bulk mixing. Interestingly, oligovaline-PHEA-C 18 exhibited an increased solubility in DMF compared with PHEA-C 18 , as demonstrated by an increase of mixing energy. In addition, increasing the mixing rate between water and DMF using the microfluidic mixer resulted in a decrease of the diameter of the resulting polymeric micelles, as compared with the particles formed from a bulk mixing process. Overall, these findings will expand the parameter space available to control particle self-assembly while also serving to improve existing nanoparticle processing techniques.

Ever since proangiogenic growth factors have been used as a vascular medicine to treat tissue ischemia, efforts have been increasingly made to develop a method to enhance efficacy of growth factors in recreating microvascular networks, especially at low dose. To this end, we hypothesized that polysaccharides substituted with sulfate groups would amplify growth factor receptor activation and stimulate phenotypic activities of endothelial cells involved in neovascularization. We examined this hypothesis by modifying alginate with a controlled number of sulfates and using it to derive a complex with vascular endothelial growth factor (VEGF), as confirmed with fluorescence resonance energy transfer (FRET) assay. Compared with the bare VEGF and with a mixture of VEGF and unmodified alginates, the VEGF complexed with alginate sulfates significantly reduced the dissociation rate with the VEGFR-2, elevated VEGFR-2 phosphorylation level, and increased the number of endothelial sprouts in vitro. Furthermore, the VEGF-alginate sulfate complex improved recovery of perfusion in an ischemic hindlimb of a mouse due to the increase of the capillary density. Overall, this study not only demonstrates an important cofactor of VEGF but also uncovers an underlying mechanism by which the cofactor mitigates the VEGF-induced signaling involved in the binding kinetics and activation of VEGFR. We therefore believe that the results of this study will be highly useful in improving the therapeutic efficacy of various growth factors and expediting their uses in clinical treatments of wounds and tissue defects.

Thermo-triggerable self-assembly was prepared by co-dissolving cinnamoyl Pluronic F127 (CinPlu) and cinnamoyl polymeric β cyclodextrin (CinPβCD) in an aqueous phase. On TEM photo, the CinPlu/CinPβCD self-assembly was 100-200nm in diameter. The specific loading of Nile red (NR) in the assembly was calculated to be 5.5% (wt NR/wt polymer), and the molar ratio of NR to βCD residue in the assembly was about 0.89:1. No significant release of NR from the assembly was observed at 10°C and 20°C. However, when the temperature was raised to 30°C, 40°C, 50°C, and 60°C, the cumulative release amount in 5min was 17%, 25%, 32%, and 52%, respectively. The specific loading of doxorubicin (DOX) in the assembly was about 6.8% (wt DOX/wt polymer) (corresponding to the molar ratio of DOX to βCD residue was about 0.41:1). The DOX release from the assembly was proportional to the temperature of release medium. NR and DOX were likely to be expelled out of the cavity of βCD residue by the interaction of the thermally hydrophobicized Pluronic F127 chain (molecular piston) and the cavity of βCD residue (cylinder). After 4h-incubation with KB cell, DOX loaded in CinPlu/CinPβCD self-assembly was found to be internalized into the cancer cell more than free DOX, observed on a confocal laser scanning microscope and a fluorescence activated cell sorter. CinPlu/CinPβCD self-assembly enhanced the in vitro anti-cancer activity of DOX against KB cell without increasing significantly the in vitro toxicity of DOX against Raw264.7 cell., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The level of endogenous estrone, one of the three major naturally occurring estrogens, has a significant correlation with the incidence of post-menopausal breast cancer. However, it is challenging to quantitatively monitor it owing to its low abundance. Here, we develop a robust and highly sensitive mass-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based quantitative platform to identify the absolute quantities of endogenous estrones in a variety of clinical specimens. The one-step modification of endogenous estrone provided good linearity (R(2) > 0.99) and significantly increased the sensitivity of the platform (limit of quantitation: 11 fmol). In addition, we could identify the absolute amount of endogenous estrones in cells of the breast cancer cell line MCF-7 (34 fmol/10(6) cells) by using a deuterated estrone as an internal standard. Finally, by applying the MALDI-MS-based quantitative method to endogenous estrones, we successfully monitored changes in the metabolic expression level of estrones (17.7 fmol/10(6) letrozole-treated cells) in MCF-7 cells resulting from treatment with an aromatase inhibitor. Taken together, these results suggest that this MALDI-MS-based quantitative approach may be a general method for the targeted metabolomics of ketone-containing metabolites, which can reflect clinical conditions and pathogenic mechanisms.

Asterina pectinifera was fermented with Cordyceps militaris mycelia for improvement of anti-oxidant activities. DPPH, alkyl, hydroxyl, and superoxide radical scavenging activities were evaluated using electron spin resonance. Anti-oxidant activities were also determined based on the ferric reducing anti-oxidant power assays and the ABTS radical scavenging activity. The lipid peroxidation inhibition activity was confirmed using ferric thiocyanate and thiobarbituric acid assays. The free radical scavenging activity and anti-oxidative effects of A. pectinifera fermented with C. militaris mycelia (FACM) extracts were higher than for A. pectinifera and C. militaris mycelia extracts alone. FACM extracts contained different biochemical ingredients due to fermentation of A. pectinifera and provide a beneficial anti-oxidant activity. FACM extracts are a promising source of beneficial antioxidants for use in food industries.

The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine for the treatment of various human ailments, including pneumonia, bronchitis, and so on, but the pharmacological applications of the leaf part of the plant have not been studied. In this study, we evaluated the various radical scavenging activities and anti-inflammatory effects of different Chaenomeles sinensis leaf (CSL) extracts. The water extract showed a higher antioxidant and radical scavenging activities. However the ethanolic extracts showed higher NO scavenging activity than water extract, therefore the ethanolic extract of CSL was examined for anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The 70% ethanol extract of CSL (CSLE) has higher anti-inflammatory activity and significantly inhibited the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, CSLE suppressed LPS-stimulated inducible nitric oxide synthase (iNOS) and NO production, IL-1β and phospho-STAT1 expression. In this study, we investigated the effect of CSLE on the production of inflammatory mediators through the inhibition of the TRIF-dependent pathways. Furthermore, we evaluated the role of CSLE on LPS-induced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Our results suggest that CSLE attenuates the LPS-stimulated inflammatory responses in macrophages through regulating the key inflammatory mechanisms, providing scientific support for its traditional uses in treating various inflammatory diseases.

In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as evidenced by western blot. Our results indicate that CF exerts anti-inflammatory effects by down-regulating expression of iNOS and COX-2 genes through inhibition of MAPK (ERK, JNK and p38) and NF-κB signaling. Similarly we also evaluated the effects of CF on LPS-induced acute lung injury. Male Balb/c mice were pretreated with dexamethasone or CF 1 h before intranasal instillation of LPS. Eight hours after LPS administration, the inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The results indicated that CF inhibited LPS-induced TNF-α and IL-6 production in a dose dependent manner. It was also observed that CF attenuated LPS-induced lung histopathologic changes. In conclusion, these data demonstrate that the protective effect of CF on LPS-induced acute lung injury (ALI) in mice might relate to the suppression of excessive inflammatory responses in lung tissue. Thus, it can be suggested that CF might be a potential therapeutic agent for ALI.

The ethanolic extract of Trapa japonica pericarp (TJP) and its various fractions were evaluated for their antioxidant potential. The ethyl acetate fraction (EF) from TJP exhibited significant antioxidant and protective effects against tert-butylhydroperoxide (t-BHP)-induced oxidative damage in vitro and in vivo. In vitro experimental results showed that the EF suppressed t-BHP-induced damage in Chang cells by inhibiting reactive oxygen species generation and regulating the mitochondrial membrane potential. Furthermore, western blot analysis showed that the EF effectively inhibited t-BHP-induced apoptosis by suppressing caspase-3, caspase-7, caspase-8, and caspase-9. In the in vivo study, the EF significantly prevented serum increases in glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and hepatic malondialdehyde levels caused by t-BHP. Furthermore, the EF markedly increased hepatic superoxide dismutase, catalase, and glutathione levels. Histopathological examinations further confirmed that the EF could protect the liver from t-BHP-induced oxidative injury. These findings indicate that the EF could be developed as a therapy or to prevent hepatic injury.

Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

The present study was performed to investigate the various radical scavenging activities of fermented Undaria pinnatifida by the mycelia fermentation method. U. pinnatifida was fermented with Cordyceps militaris (C. militaris) mycelia using solid culture and compared with unfermentated U. pinnatifida and C. militaris mycelia for antioxidant activities. The various radical scavenging activities of extracts from U. pinnatifida fermented with C. militaris mycelia (FUCM) were evaluated by electron spin resonance. The antioxidant activities of the FUCM extracts were assayed for ferric reducing antioxidant power, 2,2'-azinobis-(3- ethybenzothiazoline-6-sulfonic acid) radical scavenging activity, and oxygen radical absorption capacity. The free radical scavenging activity of FUCM extracts was higher than that of C. militaris mycelia or U. pinnatifida alone. FUCM extracts were significantly (p < 0.05) increased up to 35 times, 10 times, and 16 times that of U. pinnatifida extracts on DPPH, alkyl, and hydroxyl radical scavenging activities, respectively. These results indicate that FUCM extracts have different chemical ingredients from U. pinnatifida and could provide beneficial antioxidant activity.

Emodin, an active constituent of oriental herbs, is widely used to treat allergy, inflammation, and other symptoms. This study provides the scientific basis for the anti-inflammasome effects of emodin on both in vitro and in vivo experimental models. Bone marrow-derived macrophages were used to study the effects of emodin on inflammasome activation by using inflammasome inducers such as ATP, nigericin, and silica crystals. The lipopolysaccharide (LPS)-induced endotoxin shock model was employed to study the effect of emodin on in vivo efficacy. Emodin treatment attenuated interleukin (IL)-1β secretion via the inhibition of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation induced by ATP, nigericin, and silica crystals. Further, emodin ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin mouse models. This study is the first to reveal mechanism-based evidence, especially with respect to regulation of inflammasome activation, substantiating traditional claims of emodin in the treatment of inflammation-related disorders.

This study was undertaken to evaluate the antioxidant potential and protective effects of Celosia cristata L. (Family: Amaranthaceae) flower (CCF) extracts on tert-butyl-hydroperoxide (t-BHP)-induced oxidative damage in the hepatocytes of Chang cells and rat livers. In vitro, CCF extracts exhibited protective effect through their radical scavenging ability to enhance cell viability, prevent reactive oxygen species (ROS) generation, and inhibit mitochondrial membrane depolarisation in t-BHP-induced hepatotoxicity in Chang cells. In vivo, oral feeding of CCF (100mg and 500mg/kg of body weight) to rats for five consecutive days before a single dose of t-BHP (2mmol/kg, i.p.) showed a significant (p<0.05) protective effect by lowering serum levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). The extract decreased the hepatic levels of lipid peroxidation (MDA) and serum level of triglyceride (TG) against t-BHP-induced oxidative stress. These results indicate that CCF extract prevented oxidative stress-induced liver injury by enhancing hepatocyte antioxidant abilities., (Copyright © 2014. Published by Elsevier Ltd.)

This study demonstrates that a new method to align microparticles releasing bioactive molecules in microchannels of a hydrogel allows the guiding of growth direction and spacing of vascular networks., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely used as drug carriers for minimally invasive, local, and sustained drug delivery. However, their use is often plagued by limited controllability of encapsulation efficiency, initial burst, and release rate of drug molecules, which cause unsatisfactory outcomes and several side effects including inflammation. This study presents a new strategy of tuning the encapsulation efficiency and the release rate of protein drugs from a PLGA microsphere by filling the hollow core of the microsphere with poly(ethylene glycol) (PEG) hydrogels of varying cross-linking density. The PEG gel cores were prepared by inducing in situ cross-linking reactions of PEG monoacrylate solution within the PLGA microspheres. The resulting PEG-PLGA core-shell microspheres exhibited (1) increased encapsulation efficiency, (2) decreased initial burst, and (3) a more sustained release of protein drugs, as the cross-linking density of the PEG gel core was increased. In addition, implantation of PEG-PLGA core-shell microspheres encapsulated with vascular endothelial growth factor (VEGF) onto a chicken chorioallantoic membrane resulted in a significant increase in the number of new blood vessels at an implantation site, while minimizing inflammation. Overall, this strategy of introducing PEG gel into PLGA microspheres will be highly useful in tuning release rates and ultimately in improving the therapeutic efficacy of a wide array of protein drugs.

Hydrogels designed to sustainably release bioactive molecules are extensively used to enhance tissue repair and regenerative therapies. Along this line, numerous efforts are made to control the molecular release rate and amount. In contrast, few efforts are made to control the molecular release pattern, and, subsequently, modulate the spatial organization of newly forming tissues, including blood vessels. Therefore, using a hydrogel printed to release vascular endothelial growth factor (VEGF) into a pre-defined pattern, this study demonstrates that spatial distribution of VEGF is important in guiding growth direction of new blood vessels, and also in retaining the structural integrity of pre-existing vasculature. Guided by a computational model, we fabricated a patch composed of micro-sized VEGF-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel cylinders using an ink-jet printer. Interestingly, hydrogel printed with computationally optimized spacing created anisotropically aligned vasculature exclusively when the printed gel pattern was placed parallel to pre-existing blood vessels. In contrast, vascular sprouting from placing the printed gel pattern perpendicular to pre-existing vessels resulted in deformation and structural disintegration of the original vasculature. We envision that this study will be useful to better understand angiogenesis-modulated neovascularization and further improve the treatment quality for various wounds and tissue defects., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Adenocarcinosarcoma, a neoplasm containing both carcinomatous and sarcomatous components, is a rare form of a cancer and the pathophysiology is currently poorly understood. Moreover, definitive treatment guidelines for this disease have not yet been established. Pancreatic adenocarcinosarcoma is even more rare and the prognosis is fatal. Here, we report a case of a 77-year-old male with pancreatic adenocarcinosarcoma and metastasis to the liver. The patient presented at our hospital with uncontrolled glucose levels and diabetes mellitus. The patient's laboratory findings were unremarkable with the exception of elevated carbohydrate antigen 19-9 levels. Biopsies of the tumors in the pancreas and the liver revealed two types of tumors: pancreatic adenocarcinoma and a poorly differentiated sarcoma. To determine if KRAS mutations were present, we performed a peptide nucleic acid (PNA) clamp PCR-based assay. DNA sequencing by PNA clamp PCR identified a point mutation in codon 12 of exon 2 within KRAS from both tumor types. Because the KRAS mutation is observed in both tumor components, our findings support a monoclonal tumor origin followed by subsequent divergent differentiation into the sarcomatous and carcinomatous tumor populations. After we considered the patient's status and the late stage of tumor detection, gemcitabine chemotherapy was administered.

Intercellular adhesion modulated by cadherin molecules plays an important role in diverse cellular functions including tissue morphogenesis, regeneration, and pathogenesis. However, it is a challenging task to decipher the effects of cell-cell adhesion in vitro because of difficulty in controlling the extent and numbers of cell-cell contacts. In this study, we hypothesize that tethering recombinant extracellular domains of neural cadherin with a C-terminal immunoglobulin Fc domain (N-Cad-Fc) to a substrate with an immobilized anti-Fc antibody (Fc-antibody) and a bifunctional polymer, which is reactive to both protein and substrate, would allow us to recapitulate cell-cell adhesion, independent of the number of cells plated on the substrate. To examine this hypothesis, we first immobilized Fc-antibody to a polyacrylamide hydrogel and a methacrylate-substituted glass using poly(amino-2-hydroxyethyl-co-2-methacryloxyethyl aspartamide)-g-poly(ethylene glycol)-N-hydroxysuccinimide ester (PHMAA-g-PEGNHS) and then incubated the gel in medium containing defined concentrations of the recombinant N-Cad-Fc. The resulting N-Cad-conjugated substrate enabled us to modulate adhesion of bone marrow stromal cells to the gel surface by varying the surface density of N-Cad-Fc. In contrast, direct chemical conjugation of N-Cad-Fc to the gel surface did not support cell adhesion. Additionally, the glass substrate biologically tethered with N-Cad-Fc promoted neuronal adhesion significantly more than substrates coated with poly-l-lysine. We suggest that this novel biological tethering method could be broadly applicable for modifying substrates with a variety of classical cadherins to enable the systematic study of the effects of cadherin-modulated cell-cell adhesion on cellular activities.

In this study, Haliotis discus hannai (H. discus hannai) fermentation was attempted with Cordyceps militaris (C. militaris) mycelia using a solid culture. We tried to ferment H. discus hannai to determine the optimal conditions fermentation with regards to its anti-inflammatory effects. The extracts of H. discus hannai fermented with C. militaris mycelia (HFCM-5) showed higher nitric oxide inhibitory effects than H. discus hannai and C. militaris alone. HFCM-5 also decreased pro-inflammatory cytokines, TNF-α and IL-6 in a dose-dependent manner. HFCM-5 did not affect the MyD88-dependent pathway, but decreased phosphorylation of IRF3 and STAT1 which are involved in TRIF-dependent pathway. Taken together, our results suggest that HFCM-5 exerts its anti-inflammatory effects via TRIF signaling pathway and could potentially be used as a functional food in the regulation of inflammation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present work describes the protective effects of thymol isolated from Thymus quinquecostatus Celak. against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage through various experiments with Chang liver cells. Thymol significantly protected hepatocytes against t-BHP-induced cell cytotoxicity as demonstrated by increased viability. Furthermore, observation of Hoechst staining, annexin V/PI staining, and expression of Bcl-2 and Bax indicated that thymol inhibited t-BHP-induced Chang cell damage. Further, thymol inhibited the loss of mitochondrial membrane potential in t-BHP-treated Chang cells and prevented oxidative stress-triggered reactive oxygen species (ROS) and lipid peroxidation (malondialdehyde, MDA). Thymol restored the antioxidant capability of hepatocytes including glutathione (GSH) levels which were reduced by t-BHP. These results indicated that thymol prevents oxidative stress-induced damage to liver cells through suppression of ROS and MDA levels and increase of GSH level.

Hydrogels have been extensively studied as a carrier of various hydrophilic molecular compounds and cells for local delivery and subsequent controlled release. One of key design parameters in the hydrogel assembly is an ability to control spatiotemporal gel degradation, in order to tailor release rates of multiple drugs and also regulate phenotypic activities of co-cultured cells. To achieve this goal, this study presents a simple but innovative implantable, microfabricated hydrogel patch that undergoes micropatterned surface erosion at controlled rates and subsequently discharges two molecular compounds of interests at desired rates. This device was prepared by first fabricating a non-degradable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogel patch containing micro-pockets of controlled spacing and subsequently filling micro-pockets with a hydrogel of poly(ethylene imine) (PEI) and PEG diacrylate (PEGDA) that was tailored to degrade at controlled rates. Separate incorporation of vascular endothelial growth factor (VEGF)121 and VEGF165, known to orchestrate vascular development, into the PEI-PEGDA gel and PEGDMA hydrogel resulted in enhanced neovascularization at the implantation sites due to bimodal, sequential release of two VEGF isoforms. We believe that the hydrogel patch fabricated in this study will be highly useful to better understand a broad array of complex biological processes and also improve the efficacy of molecular cargos in varied applications., (© 2013 Elsevier Ltd. All rights reserved.)

This study presents a multi-walled poly(ethylene glycol) diacrylate hydrogel tube formed by the simple self-folding of a bi-layered hydrogel patch. The gel tube has the capability to release encapsulated molecules through designated pathways in a sustained manner. Therefore, the gel tube encapsulating the vascular endothelial growth factor significantly increases the vascular densities and vessel diameters at an implantation site., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Since stem cells emerged as a new generation of medicine, there are increasing efforts to deliver stem cells to a target tissue via intravascular injection. However, the therapeutic stem cells lack the capacity to detect and adhere to the target tissue. Therefore, this study presents synthesis of a bioactive hyperbranched polyglycerol (HPG) that can noninvasively associate with stem cells and further guide them to target sites, such as inflamed endothelium. The overall process is analogous to the way in which leukocytes are mobilized to the injured endothelium.

There is increasing evidence that matrix stiffness modulates various phenotypic activities of cells surrounded by a three-dimensional (3D) matrix. These findings suggest that matrix stiffness can also regulate dermal fibroblasts activities to remodel, repair, and recreate skin dermis, but this has not yet been systematically demonstrated to date. This study examines the effects of matrix rigidity on the morphology, growth rates, and glycosaminoglycan (GAG) production of dermal fibroblasts cultured in collagen-based hydrogels with controlled elastic moduli. The elastic moduli (E) of collagen hydrogels were increased from 0.7 to 1.6 and 2.2  kPa by chemically cross-linking collagen fibrils with poly(ethylene glycol) disuccinimidylester. Increasing E of the hydrogel led to decreases in cellular spreading, nuclear aspect ratio, and growth rate. In contrast, the cellular GAG production level was elevated by increasing E from 0.7 to 1.6  kPa. The larger accumulation of GAG in the stiffer hydrogel led to increased water retention during exposure to air, as confirmed with magnetic resonance imaging. Additionally, in a chicken chorioallantoic membrane, a cell-encapsulating hydrogel with E of 1.6  kPa created dermis-like tissue with larger amount of GAG and density of blood vessels, while a cell-hydrogel construct with E of 0.7  kPa generated scar-like tissue. Overall, the results of this study will be highly useful for designing advanced tissue engineering scaffolds that can enhance the quality of a wide array of regenerated tissues including skin.

Many diverse applications utilize hydrogels as carriers, sensors, and actuators, and these applications rely on the refined control of physical properties of the hydrogel, such as elastic modulus and degree of swelling. Often, hydrogel properties are interdependent; for example, when elastic modulus is increased, degree of swelling is decreased. Controlling these inverse dependencies remains a major barrier for broader hydrogel applications. We hypothesized that polymer cross-linkers with varied chain flexibility would allow us to tune the inverse dependency between the elastic modulus and the degree of swelling of the hydrogels. We examined this hypothesis by using alginate and poly(acrylic acid) (PAA) modified with a controlled number of methacrylic groups as model inflexible and flexible cross-linkers, respectively. Interestingly, the polyacrylamide hydrogel cross-linked by the inflexible alginate methacrylates exhibited less dependency between the degree of swelling and the elastic modulus than the hydrogel cross-linked by flexible PAA methacrylates. This critical role of the cross-linker's inflexibility was related to the difference of the degree of hydrophobic association between polymer cross-linkers, as confirmed with pyrene probes added in pregel solutions. Furthermore, hydrogels cross-linked with alginate methacrylates could tune the projection area of adhered cells by solely altering elastic moduli. In contrast, gels cross-linked with PAA methacrylates failed to modulate the cellular adhesion morphology due to a lower, and smaller, elastic modulus range to be controlled. Overall, the results of this study will significantly advance the controllability of hydrogel properties and greatly enhance the performance of hydrogels in various biological applications.

Nano-sized polymersomes functionalized with peptides or proteins are being increasingly studied for targeted delivery of diagnostic and therapeutic molecules. Earlier computational studies have suggested that ellipsoidal nanoparticles, compared to spherical ones, display enhanced binding efficiency with target cells, but this has not yet been experimentally validated. We hypothesize that hydrophilic polymer chains coupled to vesicle-forming polymers would result in ellipsoidal polymersomes. In addition, ellipsoidal polymersomes modified with cell adhesion peptides bind with target cells more actively than spherical ones. We examine this hypothesis by substituting polyaspartamide with octadecyl chains and varying numbers of poly(ethylene glycol) (PEG) chains. Increasing the degree of substitution of PEG from 0.5 to 1.0 mol% drives the polymer to self-assemble into an ellipsoidal polymersome with an aspect ratio of 2.1. Further modification of these ellipsoidal polymersomes with peptides containing an Arg-Gly-Asp sequence (RGD peptides) lead to a significant increase in the rate of association and decrease in the rate of dissociation with a substrate coated with α v β 3 integrins. In addition, in a circulation-mimicking flow, the ellipsoidal polymersomes linked with RGD peptides adhere to target tissues more favorably than their spherical equivalents do. Overall, the results of this study will greatly serve to improve the efficiency of targeted delivery of a wide array of polymersomes loaded with various biomedical modalities.

Polymer vesicles are being extensively studied to emulate self-assembly in biological systems and also use them in a variety of biological and industrial applications. This study demonstrates a novel strategy to prepare polymer vesicles in a pure aqueous medium by driving the micelle-to-vesicle transition with metallic nanoparticles. We synthesized poly(2-amino-2-hydroxyethyl aspartamide) (PAHA) substituted with octadecyl chains, which could form micelle-like self-aggregates in the aqueous medium and chemically bind with platinum precursors. Then, in situ polymerization of Pt nanoparticles within the PAHA self-aggregates generated polymer vesicles that possess nanoparticles within bilayers, because of the increase of the hydrophilic mass ratio to total mass of PAHA, f (w). This new strategy to prepare polymer vesicles would greatly serve to facilitate the control of self-assembly and ultimately improve the functionality of a wide array of polymer vesicles.

Cell-based biohybrid actuators are integrated systems that use biological components including proteins and cells to power material components by converting chemical energy to mechanical energy. The latest progress in cell-based biohybrid actuators has been limited to rigid materials, such as silicon and PDMS, ranging in elastic moduli on the order of mega (10(6)) to giga (10(9)) Pascals. Recent reports in the literature have established a correlation between substrate rigidity and its influence on the contractile behavior of cardiomyocytes (A. J. Engler, C. Carag-Krieger, C. P. Johnson, M. Raab, H. Y. Tang and D. W. Speicher, et al., J. Cell Sci., 2008, 121(Pt 22), 3794-3802, P. Bajaj, X. Tang, T. A. Saif and R. Bashir, J. Biomed. Mater. Res., Part A, 2010, 95(4), 1261-1269). This study explores the fabrication of a more compliant cantilever, similar to that of the native myocardium, with elasticity on the order of kilo (10(3)) Pascals. 3D stereolithographic technology, a layer-by-layer UV polymerizable rapid prototyping system, was used to rapidly fabricate multi-material cantilevers composed of poly(ethylene glycol) diacrylate (PEGDA) and acrylic-PEG-collagen (PC) mixtures. The incorporation of acrylic-PEG-collagen into PEGDA-based materials enhanced cell adhesion, spreading, and organization without altering the ability to vary the elastic modulus through the molecular weight of PEGDA. Cardiomyocytes derived from neonatal rats were seeded on the cantilevers, and the resulting stresses and contractile forces were calculated using finite element simulations validated with classical beam equations. These cantilevers can be used as a mechanical sensor to measure the contractile forces of cardiomyocyte cell sheets, and as an early prototype for the design of optimal cell-based biohybrid actuators.

In this paper, we review our recent work on the potential of stereolithography (SL) for different biomedical applications including tissue engineering, neovessel formation, investigating cell-cell and cell matrix interactions, and development of cellular systems. Also, we show that SL technology can be combined with dielectrophoresis (DEP) to create scaffolds with micro-scale organization, a hallmark of in vivo tissues.

Materials used in various biological applications are often modified with proteins to regulate biomolecular and cellular adhesion. Conventional strategies of protein conjugation accompany monovalent bifunctional protein linkers, which present several limitations in molecular synthesis and protein conjugation. Herein, we present a new strategy of preparing multivalent polyaspartamide linkers in a simple top-down manner, and also demonstrate that the resulting polymer linkers allow us to readily conjugate proteins to both organic and inorganic materials. The top-down synthesis of polyaspartamide linkers was performed by partially opening succinimidyl ring moieties of polysuccinimide (PSI) with the controlled number of nucleophiles reactive to photo-cross-linked hydrogel or gold-coated inorganic materials: (1) Poly(2-hydroxyethyl-co-2-methacryloxyethyl aspartamide) (PHMAA) presenting methacrylate was used to micropattern fibronectin or collagen on a hydrogel in order to regulate cell adhesion and growth area on a micrometer scale. (2) Poly(2-hydroxyethyl-co-2-mercaptoethyl aspartamide) (PHMCA) presenting thiol functional groups was used to link fibronectin to a gold-coated silicon microelectromechanical probe designed to measure cell traction force. Overall, these multivalent polyaspartamide protein linkers will greatly assist efforts to analyze and regulate the cellular adhesion to and phenotypic activities of a wide array of substrates and devices.

The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA-PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings., (Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Object: The aim of this prospective observational study was to assess the incidence and pattern of hypopituitarism after diffuse axonal injury (DAI) and to identify its effect on these patients in terms of functional outcome., Methods: Of 1307 patients with traumatic brain injury treated at the authors' institution between March 2005 and June 2008, 65 patients with DAI were enrolled in the present study. The authors determined basal hormone levels, initial Glasgow Coma Scale scores, the Marshall CT grades, the presence of abnormal signal intensity indicating lesions on MR images, and duration of unconsciousness. At the 6-month follow-up visits, functional outcomes were estimated using the Modified Barthel Index. Univariate and multivariate analyses were performed to identify factors that influenced functional outcomes., Results: Twenty-one patients with hypopituitarism (Group A) had more lesions in the body of the corpus callosum, basal ganglia, thalamus, and the gray-white matter junction than those without hypopituitarism (Group B). In Group A, growth hormone deficiency (17 patients, 80.9%) was the most common, and multiple pituitary hormone deficiencies were found in 12 patients (57.1%). The mean Modified Barthel Index score at the 6-month follow-up was 64.7 in Group A and 88.5 in Group B (p = 0.027). Duration of unconsciousness (p = 0.035), the Marshall CT grade (p = 0.021), hypopituitarism (p = 0.044), and abnormal signal intensities on MR imaging in midline or deep structures of the brain (p = 0.001) were found to be associated with functional outcome., Conclusions: The findings in this prospective observational study suggest that hypopituitarism in patients with DAI has a relationship not only with injuries in the midline or deep structures of the brain, but also with a poor outcome.

Cell-encapsulated hydrogels with complex three-dimensional (3D) structures were fabricated from photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) using modified 'top-down' and 'bottoms-up' versions of a commercially available stereolithography apparatus (SLA). Swelling and mechanical properties were measured for PEGDA hydrogels with molecular weights (M(w)) ranging from 700 to 10 000 Daltons (Da). Long-term viability of encapsulated NIH/3T3 cells was quantitatively evaluated using an MTS assay and shown to improve over 14 days by increasing the M(w) of the hydrogels. Addition of adhesive RGDS peptide sequences resulted in increased cell viability, proliferation, and spreading compared to pristine PEG hydrogels of the same M(w). Spatial 3D layer-by-layer cell patterning was successfully demonstrated, and the feasibility of depositing multiple cell types and material compositions into distinct layers was established.

Rosa rugosa is a species of rose native to eastern Asia. The root of R. rugosa has been used to treat diabetes mellitus, pain and chronic inflammatory disease, and a R. rugosa petal extract has a strong anti-oxidant effect. In the present study, we examined if solvent fractions from white rose petal extract (WRPE) had any anti-allergic or anti-atopic effects not previously reported. WRPE and butanol and hexane fractions effectively reduced systemic anaphylactic reactions and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in mice, with the greatest inhibition observed for the hexane fraction. In addition, a significant reduction of scratching behavior by mice after histamine injection suggested this fraction's potential anti-allergic effect. At the cell level, the hexane fraction markedly inhibited beta-hexosaminidase release from RBL-2H3 mast cells and suppressed the expressions of mRNA interferon-gamma and interleukin-4 cytokines produced by T helper cells (type 1 and 2). These results strongly support that the hexane fraction may have an effect on atopic dermatitis, as these 2 cell types play central roles in the pathogenesis of atopic dermatitis. In conclusion, these results suggest that either the hexane fraction or one of its components may be beneficial for the treatment of allergic diseases, including atopic dermatitis.