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It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions. [ABSTRACT FROM AUTHOR]

Despite the significant advancements of dielectric materials, the energy density values of dielectric capacitors are extremely low compared to those of other energy storage systems, e.g., batteries and fuel cells. The deposition of solid solution of ferroelectric and paraelectric multicomponent thin films are the most widely used approach to enhance the energy density of dielectric capacitors; however, it is extremely difficult to determine the optimized composition ratio of two or three components. In this study, we develop ultrahigh energy density single-component Sn-doped BaTiO 3 (BTS) epitaxial thin film capacitors. An ultrahigh energy density of 92.5 J/cm3 and energy efficiencies above 78% were successfully achieved in (111)-oriented BTS epitaxial thin film capacitors. These excellent results were attributed to the formation of multi-nanodomains accompanied by delayed polarization saturation, low remnant polarization, high breakdown strength, and high cycling stability. Engineering multi-nanodomains through chemical doping and epitaxial orientation is a facile approach to develop energy-efficient ultrahigh energy density capacitors. This approach can be extended for the design of other single-component-based energy-efficient dielectric capacitors with ultrahigh energy density. [Display omitted] [ABSTRACT FROM AUTHOR]

Applying an electric field along the [001] direction can drive the coupled polarization reversal in [100] oriented ferroelastic nano-sized a -domains in Pb(Zr,Ti)O 3 thin film. In this study, experimental probing of nanodomain evolution in ferroelastic Pb(Zr,Ti)O 3 thin films using in-situ synchrotron X-ray scattering reveals mechanisms of polarization reversal of both nanosized a-domains as well as that of matrix c-domains. Polarization reversal of a- and matrix c-domains under an electric field along the [001] direction generates the scattering intensity–electric field hysteresis loops. Both time-dependent scattering intensity and phase-field simulation reveal that the polarization reversal of nanodomains can be completed ten times faster than that of matrix c-domain owing to the ferroelastic switching mediated reversal mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract To achieve a required output voltage, a solid oxide fuel cell (SOFC) stack has multiple unit cells connected in series through interconnects (ICs). A dual-layer IC film comprising p - and n -type conducting perovskite oxides is considered to be a promising design in terms of electrical properties and stability; however, its fabrication is materials-intensive and time-consuming. Here, we propose an advanced design of a single-layer IC film inspired by the interfacial nature of the dual-layer IC film. Based on an understanding of cross-diffusion phenomena across the interface between Sr 0.7 La 0.2 TiO 3 and La 0.8 Sr 0.2 MnO 3 during the co-sintering process revealed by secondary ion mass spectroscopy, we design and synthesize mixed-cation perovskite oxides, (Sr 0.6 La 0.4) 0.9 (Ti 1– x Mn x)O 3 (SLTM), for IC applications in SOFCs. Among various compositions, Ti-rich SLTM (x = 0.25) shows high sinterability, leading to the formation of a thin, gas-tight IC film on a porous anode support via simple screen printing and sintering. When exposed to both reducing and oxidizing atmospheres, the fabricated SLTM-IC film is highly conductive and remains stable during continuous operation. The ceramic IC design proposed in this work may provide great benefits in terms of reduced costs of IC materials and fabrication, while maintaining the IC performance required for SOFCs. [ABSTRACT FROM AUTHOR]

Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Impurity has been suggested as an important factor determining toxicity following exposure to single-walled carbon nanotubes (SWCNTs). In this study, we first compared immunotoxicity based on iron content on day 90 after a single intratracheal instillation of SWCNTs in male and female mice. The inflammatory responses were generally stronger in mice exposed to acid-purified (P)-SWCNTs compared to raw (R)-SWCNTs. In addition, both R- and P-SWCNTs induced Th1-polarized immune responses with apoptotic death of BAL cells and systemically impaired the function of antigen-presenting cells (APC). We also screened reproductive and developmental toxicity by cohabitating male and female mice on day 14 after instillation. Interestingly, the pregnancy rate rapidly decreased following exposure to both types of SWCNTs, especially R-SWCNTs. In addition, we investigated developmental immunotoxicity of the offspring on day 28 after exposure to both types of SWCNTs. Their hematological changes were clearer relative to those of the parents and a significant decrease in the alkaline phosphatase and potassium levels was observed in mice of both sexes exposed to the higher dose of R- and P-SWCNTs. In conclusion, we suggest that SWCNTs may induce Th1-polarized immune responses accompanied by suppression of APC function on day 90 after a single instillation without significant iron content dependance. In addition, the consecutive exposure of SWCNTs to the subsequent generation may exacerbate metabolic and hematological disturbance. Furthermore, our results underscore the need to clarify the reproductive and developmental health effects of SWCNTs. [ABSTRACT FROM PUBLISHER]

The transcription factors, Runx2 and Osterix (Osx), act downstream in the BMP2 pathway, and they are essential for osteoblast differentiation and bone formation. While Runx2 expression is normal in Osx-null mice, Osx is not expressed in Runx2-null mice, indicating that Osx acts downstream of Runx2 during bone formation. Runx2 and Osx are also independently regulated during bone formation. To define the unknown correlation between Runx2 and Osx in the regulation of bone formation, we analyzed the bone of Runx2/Osx double heterozygotes generated by mating heterozygous Runx2 and Osx mice and elucidated the differential gene expressions due to the lack of Runx2 and Osx in bone. Compared to the Runx2 and Osx heterozygous embryos, Runx2/Osx double heterozygous embryos showed reduced bone length in the humerus and femur as well as hypoplastic or complete absence of the maxillary and palatine shelf, presphenoid bone, zygomatic bone, and tympanic ring. Severe inward bending was observed in the ribs and humerus. Histological analysis showed an expanded region of hypertrophic chondrocytes and a reduced area of mineralized bones in the Runx2/Osx double heterozygous embryos. DNA microarray analysis of the calvaria of embryos allowed gene classification based on similarities in the upregulated and downregulated expression patterns. Clusters 1 and 2 include 68 downregulated genes and 18 upregulated genes, respectively, in the Runx2/Osx double heterozygous embryos. Finally, the skeletal analysis and gene expression profiles obtained by clustering may facilitate the understanding of the correlation between Runx2 and Osx in skeletal development. [ABSTRACT FROM AUTHOR]

Highlights: [•] A PEDOT:PSS layer was nanopatterned in OPV cells. [•] The nanopatterned PEDOT:PSS layer improved light scattering and absorption. [•] The PEDOT:PSS improved the efficiency of the OPV cells. [Copyright &y& Elsevier]

Abstract: Nuclear factor of activated T cells (NFAT) is an important transcription factor for the production of interleukin (IL)-2 upon T-cell receptor (TcR) signaling. Therefore, inhibition of the NFAT–carcineurin pathway is an important target for inflammatory disease inhibition and graft rejection. A novel cell permeable peptide (CPP), Sim-2, has been identified from a human transcription factor, and Sim-2-CPP conjugated to β-galactosidase or EGFP protein was efficiently delivered into cells in vitro and in vivo. A cell permeable form of the NFAT inhibitory peptide VIVIT (Sim-2-VIVIT) was synthesized and showed inhibitory effects on human CD4 or CD8 T-cell activation through NFAT transcriptional activity suppression and IL-2 inhibition. Intranasal administration of the Sim-2-VIVIT peptide in an ovalbumin (OVA)-induced murine asthma model alleviated peribronchial and perivascular infiltration of inflammatory cells in the lung and caused airway remodeling and airway hyper-responsiveness. These results suggest that cell permeable Sim-2-VIVIT peptide has clinical potential as an immunosuppressive agent for inflammatory diseases. [Copyright &y& Elsevier]

Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARΓ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4 T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease. [ABSTRACT FROM AUTHOR]

CONTEXT: There is an increasing need for the comparative assessment of palliative care services; however, few systematic empirical studies have been performed to determine the most feasible, representative, efficient survey method. OBJECTIVES: To investigate the feasibility, representativeness, and efficiency of several survey methods. METHODS: This study was performed as a part of a national initiative to develop a system to evaluate the quality of palliative care services. Three separate but related surveys of patients, caregivers, and bereaved family members were conducted. These surveys were designed to simulate an independent assessment in a nationwide quality evaluation project. RESULTS: The effective response rates for the patient, caregiver, and bereavement surveys were 30.4% (105 of 344), 46.5% (160 of 344), and 20.9% (501 of 2398), respectively. Subjects who responded to the patient and caregiver surveys were likely to have better physical and mental conditions, whereas subjects who responded to the bereaved family survey did not differ significantly from nonrespondents in regard to patient characteristics, except for a small difference in patient gender (females: 47.2% vs. 41.7%, P=0.028). The average number of responses per institution was 3.2, 4.8, and 15.2, respectively. The cost of the patient and caregiver surveys was much higher than the cost of the bereaved family member survey. CONCLUSION: There were significant differences between the three methods. Despite the low response rate, our findings suggest that the bereaved family member survey has strengths in terms of feasibility and efficiency, and could be considered as a practical option for the comparative assessment of palliative care services by an independent body. [ABSTRACT FROM AUTHOR]

CONTEXT: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) is a shortened version of the EORTC QLQ-C30, developed for use in advanced cancer patients. OBJECTIVES: We evaluated the psychometric properties of the Korean version of the EORTC QLQ-C15-PAL to determine if this tool can be used to evaluate Korean patients with cancer who receive palliative care. METHODS: A multicenter, cross-sectional survey was performed in palliative care units and hospices in Korea from September to October 2009. A total of 102 patients with cancer completed the questionnaires that included the EORTC QLQ-C15-PAL. RESULTS: The compliance rate was high, with the missing rate for each item ranging from 0% to 7.8% (mean 3.1%). A multitrait scaling analysis revealed good convergent and discriminant validity, with only three scaling errors. The Cronbach's alpha coefficients ranged from 0.65 to 0.89. The questionnaire discriminated among patient subgroups with different clinical profiles (e.g., performance status and degree of oral intake), thereby demonstrating the clinical validity of this tool. CONCLUSION: Our findings indicate that the Korean version of the EORTC QLQ-C15-PAL is a reliable and valid instrument with regard to its psychometric properties. This tool is suitable for measuring quality of life, particularly with regard to physical aspects, in Korean cancer patients who receive palliative care.Copyright © 2011 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Abstract: The present study describes the fabrication of a novel microchannel with 60 electrodes and the electrical resistance measurement in different flow types in the microchannel system. This microchannel is designed for ERT application, which has five measurement cross sections and embeds 12 electrodes in each cross section. The microchannel has been successfully fabricated by MEMS processes which are comprised of photolithography of platinum wire on quartz glass layers, compression to fabricate the electrode layers, and micro mechanical processing for the flow groove. After the microchannel fabrication, the connector is constructed in order to avoid unstable measurement condition between the microchannel electrodes and the resistance measurement system. The electrical resistances between the electrode pairs of the microchannel were measured in the case of tap water, particle flow and the separately injected tap water plus particle flow. The electrical resistances are reasonably and stably measured in the microchannel. [ABSTRACT FROM AUTHOR]

Abstract: T-cell activation requires TcR-mediated and co-stimulatory signals. ZAP-70 participates in the initial step of TcR signal transduction, while a co-receptor, CTLA-4, inhibits T-cell activation. In previous studies, the overexpression of a ZAP-70 mutant (ZAP-70-Y319F) inhibited the TcR-induced activation of NFAT and IL-2 production, while Hph-1-ctCTLA-4 prevented allergic inflammation. To develop an effective immunosuppressive protein drug that blocks both TcR-mediated and co-stimulatory signaling pathways, a fusion protein of ZAP-70-Y319F and the Hph-1 protein transduction domain was generated. Hph-1-ZAP-70-Y319F inhibited the phosphorylation of ZAP-70-Tyr319, LAT-Tyr191, and p44/42 MAPK induced by TcR stimulation, NFAT- and AP-1-mediated gene transcription, and the induction of CD69 expression and IL-2 secretion. Hph-1-ZAP-70-Y319F and Hph-1-ctCTLA-4 synergistically inhibited signaling events during T-cell activation. This is the first report to demonstrate the synergistic inhibition of signals transmitted via TcR and its co-stimulatory receptor by cell-permeable forms of intracellular signal mediators. [Copyright &y& Elsevier]

Abstract: Currently, wavelet transforms are widely used for the analyses of particle image velocimetry (PIV) velocity vector fields. This is because the wavelet provides not only spatial information of the velocity vectors, but also of the time and frequency domains. In this study, a discrete wavelet transform is applied to real PIV images of bubbly flows. The vector fields obtained by a self-made cross-correlation PIV algorithm were used for the discrete wavelet transform. The performances of the discrete wavelet transforms were investigated by changing the level of power of discretization. The images decomposed by wavelet multi-resolution showed conspicuous characteristics of the bubbly flows for the different levels. A high spatial bubble concentrated area could be evaluated by the constructed discrete wavelet transform algorithm, in which high-leveled wavelets play dominant roles in revealing the flow characteristics. [Copyright &y& Elsevier]

Exploring the unique physical properties of oxide perovskites necessitates their growth on diverse single‐crystal substrates. The thin‐film growth of perovskite SrMnO3 (SMO) has been a particular focus of research due to its emerging room‐temperature multiferroicity. Herein, the epitaxial thin films of (110)‐oriented SMO are grown on the piezoelectric (110)‐oriented (1–x)Pb(Mg1/3Nb2/3)O3–xPbTiO3 (PMN‐PT) substrate. The effects of the thickness and oxygen annealing on the crystal structure, stoichiometry, and ferroelectric properties of the SMO thin film are systematically investigated. The tensile strain produced by the lattice mismatch between the bulk SMO and the PMN‐PT substrate causes an expansion of the c‐lattice parallel to the in‐plane direction of the substrate. The films show larger a‐, b‐, and c‐lattice parameters than the bulk material, resulting in volume expansion of the unit cell. This lattice expansion is attributed to the generation of oxygen vacancies driven by the reduced formation energy caused by the high elastic strain. Piezoelectric force microscopy reveals that the SMO film contains domains with strain‐mediated in‐plane and vacancy‐mediated out‐of‐plane polarization. Furthermore, the piezoelectric response of the PMN‐PT substrate effectively modulates the biaxial tensile strain in the SMO film, offering a potential strategy for controlling the crystal structure and ferroelectric properties of SMO. [ABSTRACT FROM AUTHOR]

The discovery of ferroelectricity in HfO2 ultrathin films has gathered considerable interest from the microelectronic industry owing to their compatibility with complementary metal oxide semiconductor technology. However, a significant challenge in utilizing HfO2 thin films for commercial devices is the wakeup effect, which is an increase in polarization with the number of electric field cycles in HfO2-based capacitors. Despite efforts to develop wakeup-free HfO2 thin films, the root cause of this effect remains elusive. Some studies attribute it to the tetragonal (T) to orthorhombic (O) phase transformation, while others suggest it is due to the redistribution of oxygen vacancies within the HfO2 layer during electric field cycling. This study investigated the phase transformation dynamics and oxygen vacancy distributions in TiN/Hf0.5Zr0.5O2/TiN capacitors subjected to electric field cycling using in situ grazing incidence synchrotron x-ray diffraction and ex situ x-ray photoelectron spectroscopy. The as-grown HZO films were crystallized in a mixed phase consisting of monoclinic (M), tetragonal, and orthorhombic fractions. The T-phase volume fraction decreased continuously up to 10k electric field cycles. In contrast, the O-phase fraction increased within the first 100 cycles and then stabilized with further cycling. The redistribution of oxygen vacancies occurred continuously throughout the cycling process. The results revealed that continuous oxygen vacancy redistribution during electric field cycling resulted in phase transformation between the T-, O-, and M-phases. The study provides insight into the phase transformation dynamics and oxygen vacancy redistribution in TiN/Hf0.5Zr0.5O2/TiN capacitors during electric field cycling, shedding light on the underlying mechanisms of the wakeup effect. [ABSTRACT FROM AUTHOR]

Offshore platforms with ship-like hull structures have relatively low roll damping moment. In this paper, variations of roll reduction appendages based on increasing damping strategy are proposed. The appendages are an ordinary bilge keel, a newly adopted variation involving extended platforms with ship-like hull structures, such as drillships or reversed flaps, and a stinger type. To validate the roll damping performance of newly designed appendages, a series of free-decay data for the roll motion in calm water and in regular waves are obtained from towing tank tests. The free-decay data for the roll motion is analyzed using a linear-plus-quadratic damping method as well as an alternative method based on the Hilbert transform in order to overcome the possible problem of nonlinearity for non-conventional roll stabilizers. The Hilbert transform technique has the advantage over polynomial damping models for not assuming the form of the roll characteristics. A comparison of the analysis methods for the different appendages is carried out for linear, nonlinear, and equivalent linear damping methods. The results are crosschecked in regular beam waves for different amplitudes near their resonant frequencies. From the experimental analysis, the linear and nonlinear roll characteristics for various appendages are discussed. [ABSTRACT FROM AUTHOR]

Rubber-tired light rail vehicles are generally operated on lines which include a number of small curves, steep slopes, or track switching sections to reduce construction costs or to place multiple stations in densely populated areas. Recently, the tendency is to increase acceleration, deceleration, and operation speed to shorten travel time and to increase transportation capacity. These track characteristics and operation patterns may result in deteriorating lateral dynamic characteristics in rubber-tired light rail vehicles. Therefore, running gear in rubber-tired light rail vehicles needs to play a role in effectively damping lateral vibrations and shock transmitted from the guidance rails through the guidance wheels. In this paper, new running gear was proposed to improve the lateral vibration and ride comfort in rubber-tired light rail vehicles. The new running gear has been newly installed with lateral rubber shock absorbers that can dampen lateral vibration on curved routes. In addition, it has been installed with a bi-directional return spring in place of the existing restoring coil spring and hydraulic damper to improve lateral vibration on straight routes. The effect of improving the lateral dynamic characteristics of the new running gear was verified through dynamic analysis and actual vehicle driving tests (field tests). [ABSTRACT FROM AUTHOR]

TGF-β signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-β signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage integrity remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-β signaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks of age and developed OA at 12 months. Cbfb△ac/△ac mice showed enhanced OA progression under the surgically induced OA model in mice. Mechanistically, forced expression of Cbfβ rescued Type II collagen (Col2α1) and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-β1-mediated Col2α1 expression failed despite the p-Smad3 activation under TGF-β1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-β signaling pathway in articular cartilage. [ABSTRACT FROM AUTHOR]

CONTEXT: A reliable and valid measure of structure and process of end-of-life care is important for improving the outcomes of care. OBJECTIVES: This study examined the validity and reliability of the Korean version of Care Evaluation Scale (CES), which was developed in Japan to evaluate structure and process of palliative care from the perspective of bereaved family members. METHODS: Standard forward-backward translation and a pilot test were conducted. A multicenter cross-sectional survey was conducted with bereaved family members (n=501) of patients who had died from cancer two to six months before the study. Descriptive analyses were performed. The reliability of the CES was tested by Cronbach's alpha. The dimensional structure was assessed using confirmatory factor analyses. Concurrent and discriminant validity were tested by correlation with the overall satisfaction with care, patient's overall quality of life (QoL), and family member's own QoL as measured by the EQ-5D. RESULTS: Participants could complete the CES readily, with low missing response rates. Cronbach's alpha for internal consistency was 0.93 overall, and ranged from 0.88 to 0.94 for subdomains. The hypothesized 10 subscale model of the CES appeared to fit the data (goodness-of-fit index=0.854). The overall score of the CES moderately correlated with overall satisfaction with care (r=0.54, P<0.001), more weakly correlated with the patient's QoL (r=0.32, P<0.001), but did not correlate with the family member's QoL (r=0.03, P=0.548). CONCLUSION: The CES was found to be a reliable and a valid measure of the necessity for improvement in the structure and process of end-of-life care from bereaved family members' perspectives. [ABSTRACT FROM AUTHOR]

An addendum to the article "Patterning of ferroelectric nanodot arrays using a silicon nitride shadow mask," by Hyung-Joon Shin and colleagues published in Vol. 87 of 2005 is presented.

Mg doped a-plane GaN layers with MgN interlayers were grown on r-plane sapphire substrates by metal–organic chemical vapor deposition. Nonpolar Mg doped a-plane GaN without MgN exhibited a rough surface morphology, with both various sized, and large number of faceted pits. Meanwhile, nonpolar p-type GaN layers using MgN exhibited improved surface morphology, with typical stripe features along the [0 0 0 1] direction, and reduced faceted triangular pits on the surface, leading to increased hole concentration and crystal quality. The effect of insertion of MgN interlayers and their characteristics in Mg doped a-plane GaN were estimated by Hall-effect measurement, atomic force microscopy (AFM), cathode luminescence (CL), X-ray diffraction (XRD), and transmission electron microscope (TEM) measurement. [ABSTRACT FROM AUTHOR]

With the advent of cancer immunotherapy, immunomodulation has emerged as an important strategy for the treatment of various diseases. We review recent advances in clinical trials of cell-penetrating peptide (CPP) applications for immunotherapy and also discuss their challenges and opportunities for preclinical studies in various immune diseases. CPP conjugation to antigenic peptides or proteins can enable efficient antigen uptake and cross-presentation by antigen-presenting cells (APCs), which induce both humoral and cytotoxic responses. In addition, CPP-coupled immune modulators can enhance antitumor immunity or anti-inflammatory effects to regulate allergies and autoimmunity. Given their huge advantages in overcoming delivery barriers, CPP-based strategies for immunomodulation could extend drug optimization and advance immunotherapy in various human diseases. CPP conjugates can penetrate tissue barriers such as the blood–brain barrier and skin, that are difficult for other drugs to pass. CPP-conjugated antigen delivery in APCs or directly in vivo can increase the cytotoxic T lymphocyte (CTL) response as well as the antibody response by cross-presentation. CPP-conjugated cell fate controlling peptides or proteins can modulate lymphocyte function such as increasing regulatory T cell differentiation or inhibiting type 17 T helper cells to regulate autoimmunity, allergy, or organ transplantation. CPP-mediated molecular delivery for enhancing the type 1 T helper cell or CTL responses results in antitumor immunity and can enhance the efficacy of immune checkpoint inhibitors. There have been recent significant advances in clinical trials addressing human diseases using CPPs, such as CPP-coupled botulinum toxin A for cervical dystonia, TAT–PSD-95 for ischemic stroke, and TAT–JNKI-1 for hearing loss. [ABSTRACT FROM AUTHOR]

The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway plays important roles in the development and growth of the skeleton. Apert syndrome caused by gain‐of‐function mutations of FGFR2 results in aberrant phenotypes of the skull, midface, and limbs. Although short limbs are representative features in patients with Apert syndrome, the causative mechanism for this limb defect has not been elucidated. Here we quantitatively confirmed decreases in the bone length, bone mineral density, and bone thickness in the Apert syndrome model of gene knock‐in Fgfr2S252W/+ (EIIA‐Fgfr2S252W/+) mice. Interestingly, despite these bone defects, histological analysis showed that the endochondral ossification process in the mutant mice was similar to that in wild‐type mice. Tartrate‐resistant acid phosphatase staining revealed that trabecular bone loss in mutant mice was associated with excessive osteoclast activity despite accelerated osteogenic differentiation. We investigated the osteoblast–osteoclast interaction and found that the increase in osteoclast activity was due to an increase in the Rankl level of osteoblasts in mutant mice and not enhanced osteoclastogenesis driven by the activation of FGFR2 signaling in bone marrow‐derived macrophages. Consistently, Col1a1‐Fgfr2S252W/+ mice, which had osteoblast‐specific expression of Fgfr2 S252W, showed significant bone loss with a reduction of the bone length and excessive activity of osteoclasts was observed in the mutant mice. Taken together, the present study demonstrates that the imbalance in osteoblast and osteoclast coupling by abnormally increased Rankl expression in Fgfr2S252W/+ mutant osteoblasts is a major causative mechanism for bone loss and short long bones in Fgfr2S252W/+ mice. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to compare the effects of two different resorbable collagen membranes on new bone formation after sinus grafts with anorganic bovine bone mineral ( BBM). Materials and methods For 64 patients presenting with an initial residual bone height ≤4 mm at the posterior maxilla, the sinus floors were grafted with BBM ( Bio- Oss®). The lateral windows were covered by one of the two bio-resorbable membranes, Bio- Arm® or Bio- Gide®. The histomorphometric data were obtained 7-15 months after sinus augmentation at the time of the implant installation. Results The core biopsy specimens of Bio- Arm ( n = 37 sites) and Bio- Gide group ( n = 22 sites) were compared. The results showed that the BBM particles were in direct contact with the newly formed bone in all cases. In histomorphometric analysis, the Bio- Gide group showed significantly higher new bone formation (33.3 ± 12%) compared with the Bio- Arm group (26.3 ± 8.1%) ( P < 0.05). All the implants survived successfully after a mean follow-up of 35.3 months (range 22-63 months) in the Bio- Arm group and 55.5 months (range 35-66 months) in the Bio- Gide group. The amount of new bone in the specimens did not significantly correlate with the residual bone height at the time of surgery or the length of the healing period. Conclusions The type of resorbable membrane did not readily affect the long-term survival of the implants at the grafted sinus. On the other hand, Bio- Gide group showed more new bone formation than the Bio- Arm group, which implied that the function of the membrane can influence the remodeling of the grafted sinus. As the amount of residual bone substitute particle had not decreased significantly over time, the results suggest that the BBM was rarely resorbable for at least 15 months after the surgery. [ABSTRACT FROM AUTHOR]

Abstract: BAX Inhibitor-1 (BI-1), a transmembrane protein on the endoplasmic reticulum, has been studied previously in various physio/pathological conditions, but not in bone cells. In this study, using the MG63 osteoblast cell line and osteoblasts differentiated from stem cells, the role of BI-1 was studied. First, expression of BI-1 was confirmed in osteoblasts, as well as osteoclasts, in mouse tibiae bone immunohistochemistry. For evaluation of a recently published property of BI-1, an acidic pH-dependent Ca2+ channel-like effect in osteoblasts, acidic pH-associated cell death, and pro-inflammatory cytokine release were examined. In MG63 osteoblasts, acidic pH induced a pH-dependent increase in cell death and ER stress, as determined by elevated expression of GRP78, CHOP, phospho-eIF2α, IRE-1α, spliced XBP-1, and phospho-JNK. In osteoblasts, mitochondrial Ca2+ also showed a strong pH-dependent increase. BI-1 knock-down using siRNA protected cells against acidic pH, regulating mitochondrial Ca2+ accumulation, possibly via the acidic pH-dependent Ca2+ channel-like effect of BI-1. BI-1 knock-down also resulted in inhibition of acidic pH-induced release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. In addition, bone marrow stem cells were differentiated into human osteoblasts, which showed increased expression of BI-1 mRNA and protein. In differentiated primary human osteoblasts, acidic pH-associated cell death, mitochondrial Ca2+ accumulation, and pro-inflammatory cytokine release were more significant than in non-differentiated stem cells. In summary, endogenous expression of BI-1 is associated with acidic pH-induced Ca2+ release, cell death, and pro-inflammatory cytokine release in human osteoblasts. [Copyright &y& Elsevier]

Abstract: In the present paper, the extraction of dominant particle concentration fluctuation at various time–space frequency levels from reconstructed electrical capacitance tomography (ECT) images by means of the discrete wavelet transform has been proposed. Using this concept, three-dimensional images (time and two-dimensional space) obtained by an ECT system are decomposed into different time and space levels to characterize the intrinsic features of the particle distribution in a down-flow fluidized bed with a newly designed distributor using three-dimensional discrete wavelet multiresolution. As a result, the dominant time and space particle distribution characteristics for a specific frequency level can be visualized. On the basis of the wavelet analysis results, the best operation condition, under which the most stable and uniform particle distribution can be obtained, was clarified. This provides a good reference for the optimization of a downer reactor to qualify the refinery process in the petroleum industry. [Copyright &y& Elsevier]

Hypoxia, inflammation, and acidity occur after bone fracture. To simplify the fracture model, we tested the effects of acidity in osteoblasts. We tested three osteoblast cell lines, MG63, MC3T3E1, and HOS cells, with MG63 cells showing much higher sensitivity to acidic pH. In physiologically acidic surroundings, pH 7.2, the endoplasmic reticulum stress response was measured through the expression of unfolded protein response proteins. Acidic surroundings time-dependently increased IL-6 secretion. Cathepsin B, a marker of the inflammation and angiogenic processes that occur after bone fracture, also increased. Thus, acidity can cause ER stress, increase IL-6, and increases cathepsin B expression in osteoblasts. [ABSTRACT FROM AUTHOR]

Abstract: An assessment of chungkukjang (traditional fermented soyfood) fermented at 42°C for 72h with six sample groups of Korean black soybean (Glycine max) was carried out. Total phenol and isoflavone contents of large black soybean (LBS) group extracts were higher than that of small black soybean (SBS) group extracts. Genistein contents were higher than daidzein in all groups. In total anthocyanin pigment, LBS groups were similar to SBS groups. LBS group extracts exhibited good inhibition rate of about 70–90% in antioxidant and some scavenging activities of free radicals as well as hydrogen peroxide. Bacillus megaterium SMY-212 was a suitable fermenting strain to promote the antioxidant and free-radical scavenging activities in cooked black soybean. [Copyright &y& Elsevier]

In the present study, the in vitro biocompatibility of calcium metaphosphate (CMP) with human bone marrow stromal cells (HBMSCs) and its effect on osteoblastic differentiation have been investigated. Powder and disk forms of CMP do not exert a cytotoxic effect on the HBMSCs undergoing osteoblastic differentiation. In addition, the HBMSCs adhere to the surface of the CMP disk as successfully as to the culture plate or hydroxyapatite (HA) disk. The HBMSCs adhered to either the HA or CMP disk display an undistinguishable actin arrangement and cellular phenotypes, indicating that the CMP does not disrupt normal cellular responses. An analysis of the differentiation of the HBMSCs cultured on culture plate, the HA and the CMP disk shows that three matrices are capable of supporting osteoblastic differentiation of the HBMSCs as accessed by alkaline phosphatase (ALP) staining. Further molecular analysis of osteoblastic differentiation of HBMSCs reveals that the CMP disk has a better ability than the HA disk to induce an expression of osteoblast-related genes, including ALP, osteoprotegerin (OPG), a decoy receptor for RANK ligand, and osteopontin (OPN), a non-collagenous bone matrix protein. The results demonstrate that, in addition to favorable biocompatibility, the CMP can stimulate osteoblastic differentiation of the HBMSCs in vitro. [Copyright &y& Elsevier]

The Runx2/Cbfa1 transcription factor regulates a program of gene expression necessary for skeletal development. To understand signals mediating skeletal formation, we examined the in vivo spatio-temporal activity of the Runx2 P1 promoter which controls expression of the bone-related Type II isoform. Transgenic mice carrying 3 kb of Runx2 promoter fused to the lacZ gene exhibit localized promoter activity in early mesenchymal condensations shortly after the embryonic turning event. Expression in developing mesenchyme continues throughout chondrogenesis and is restricted to the axial skeleton. Our data support a function for Runx2 in establishment of the prechondrocytic skeletal primordium. [Copyright &y& Elsevier]

Hypoxic environment is essential for chondrocyte maturation and longitudinal bone growth. Although hypoxia‐inducible factor 1 alpha (Hif‐1α) has been known as a key player for chondrocyte survival and function, the function of Hif‐2α in cartilage is mechanistically and clinically relevant but remains unknown. Here we demonstrated that Hif‐2α was a novel inhibitor of chondrocyte maturation through downregulation of Runx2 stability. Mechanistically, Hif‐2α binding to Runx2 inhibited chondrocyte maturation by Runx2 degradation through disrupting Runx2/Cbfβ complex formation. The Hif‐2α‐mediated‐Runx2 degradation could be rescued by Cbfβ transfection due to the increase of Runx2/Cbfβ complex formation. Consistently, mesenchymal cells derived from Hif‐2α heterozygous mice were more rapidly differentiated into hypertrophic chondrocytes than those of wild‐type mice in a micromass culture system. Collectively, these findings demonstrate that Hif‐2α is a novel inhibitor for chondrocyte maturation by disrupting Runx2/Cbfβ complex formation and consequential regulatory activity. [ABSTRACT FROM AUTHOR]

Regulatory T cells play a key role in immune tolerance to self‐antigens, thereby preventing autoimmune diseases. However, no drugs targeting Treg cells have been approved for clinical trials yet. Here, a chimeric peptide is generated by conjugation of the cytoplasmic domain of CTLA‐4 (ctCTLA‐4) with dNP2 for intracellular delivery, dNP2‐ctCTLA‐4, and evaluated Foxp3 expression during Th0, Th1, Treg, and Th17 differentiation dependent on TGF‐β. The lysine motif of ctCTLA‐4, not tyrosine motif, is required for Foxp3 expression for Treg induction and amelioration of experimental autoimmune encephalomyelitis (EAE). Transcriptome analysis reveals that dNP2‐ctCTLA‐4‐treated T cells express Treg transcriptomic patterns with properties of suppressive functions. In addition, the molecular interaction between the lysine motif of ctCTLA‐4 and PKC‐η is critical for Foxp3 expression. Although both CTLA‐4‐Ig and dNP2‐ctCTLA‐4 treatment in vivo ameliorated EAE progression, only dNP2‐ctCTLA‐4 requires Treg cells for inhibition of disease progression and prevention of relapse. Furthermore, the CTLA‐4 signaling peptide is able to induce human Tregs in vitro and in vivo as well as from peripheral blood mononuclear cells (PBMCs) of multiple sclerosis patients. These results collectively suggest that the chimeric CTLA‐4 signaling peptide can be used for successful induction of regulatory T cells in vivo to control autoimmune diseases, such as multiple sclerosis. [ABSTRACT FROM AUTHOR]

Midface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2S252W mutation (Col2a1-cre; Fgfr2S252W/+) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. In Col2a1-cre; Fgfr2S252W/+ mice, skull shape was normal at birth, but hypoplastic phenotypes became evident with age. General dimensional changes of mutant mice were comparable with those of mice with mutations in EIIa-cre; Fgfr2S252W/+, a classic model of Apert syndrome in mice. Col2a1-cre; Fgfr2S252W/+ mice showed some unique facial phenotypes, such as elevated nasion, abnormal fusion of the suture between the premaxilla and the vomer, and decreased perpendicular plate of the ethmoid bone volume, which are related to the development of the nasal septal cartilage. Morphological and histological examination revealed that the presence of increased septal chondrocyte hypertrophy and abnormal thickening of nasal septum is causally related to midface deformities in nasal septum-associated structures. Our results suggest that careful examination and surgical correction of the nasal septal cartilage may improve the prognosis in the surgical treatment of midface hypoplasia and respiratory problems in patients with Apert syndrome. [ABSTRACT FROM AUTHOR]

Study design: This is a retrospective cohort comparative study. Background: Vitamin D supplementation is considered to be associated with good functional outcome. Thus, a few studies have proposed vitamin D supplementation is benefit to the functional outcome in LSS requiring surgery. The purpose of this study is to identify the prevalence of vitamin D deficiency in patients with LSS requiring surgery, and to compare the differences between the cases whether vitamin D is supplemented and vitamin D is not supplemented in terms of a QoL during postoperative 2 year. Methods: All patients with LSS who underwent surgery from March 1, 2015 to August 31, 2016 were enrolled. Among them, 61 patients with vitamin D deficiency were divided into two groups (supplemented group (A) and non-supplemented group (B)). Functional outcomes using Oswestry Disability Index (ODI) and Rolland Morris Disability Index (RMDQ) and QoL using SF-36 were evaluated at 12-month and 24-month follow-up periods. Differences in functional score and SF-36 between the vitamin D supplemented and non-supplemented group were compared. Results: Among the total 102 patients, 78 patients (76.5%) had vitamin D deficiency. Of the 78 patients, 61 patients were included, 27 patients were group A and 27 patients were group B. There was no difference in age and 25-OHD level between the two groups (all 0 > 0.05). Group A were better functional outcomes at 2 years after surgery (p < 0.05). On the QoL, group A were higher score than group B from 12 month later after surgery (p < 0.05). Conclusions: Vitamin D deficiency was highly prevalent in LSS patients (76.5%). Assessment of serum 25-hydroxyvitamin D (25(OH)D) is recommended in LSS needing surgical intervention and active treatment vitamin D supplementation and maintenance of normal range should be considered for better postoperative functional outcome and QoL. [ABSTRACT FROM AUTHOR]

G protein‐coupled receptor 119 (GPR119) is known to be a promising therapeutic target for type 2 diabetes. Recently, it has been reported that the GPR119 agonist increases bone mineral density in an animal model of diabetes, suggesting that GPR119 may play a key role in bone metabolism. In this study, we investigated the functional role of GPR119 in receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation. We found that the GPR119 expression was markedly increased in preosteoclasts and then downregulated in mature osteoclasts. Activation of GPR119 with AS1269574, a potent selective agonist for GPR119, inhibited the generation of multinuclear osteoclasts from bone marrow‐derived macrophages. Confirming this observation, targeted silencing of GPR119 using short hairpin RNA abrogated the AS1269574‐mediated suppressive effect on osteoclast formation. GPR119 activation attenuated the expression of c‐Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) and blocked RANKL‐stimulated phosphorylation of IκBα, c‐Jun N‐terminal protein kinase (JNK), and extracellular signal‐regulated kinase (ERK) but not p38. In addition, GPR119 activation suppressed preosteoclast fusion by downregulating the expression of the dendritic cell‐specific transmembrane (DC‐STAMP), a molecule that is essential for cell–cell fusion in osteoclast formation. Furthermore, ectopic expression of DC‐STAMP restored AS1269574‐mediated inhibition of osteoclast fusion. Taken together, our findings demonstrate that GPR119 plays a negative role in osteoclast differentiation and fusion induced by RANKL, and therefore may represent a potential target for bone resorption‐associated diseases. G protein‐coupled receptor 119 (GPR119) activation inhibits osteoclastogenesis and fusion induced by receptor activator of nuclear factor‐κB ligand (RANKL). GPR119 may become a new target for the treatment of bone‐erosive diseases characterized by increased osteoclast number. [ABSTRACT FROM AUTHOR]

Angiogenesis plays an important role in active inflammation and wound healing. Our results showed that silk sericin and 4-hexylresorcinol (4HR) increased vascular endothelial growth factor (VEGF) expression in a dose-dependent manner in RAW264.7 cells. Unlike 4HR, silk sericin increased the expression of hypoxia inducible factor-1α (HIF-1α) and HIF-2α. Pretreatment with an HIF inhibitor decreased the sericin-induced increase in VEGF expression. However, the HIF inhibitor did not affect the 4HR-induced increase in VEGF expression. An inhibitor of matrix metalloproteinase (MMP) declined the 4HR-induced increase in VEGF expression. Silk sericin increased production of reactive oxygen species (ROS), whereas 4HR decreased ROS. M1 markers were increased by silk sericin treatment, and M2 markers were increased by 4HR treatment. VEGF and angiogenin expression were higher in rats treated with a 4HR-incorporated silk mat than in rats treated with a silk mat alone. In conclusion, silk sericin and 4HR increased VEGF expression in RAW264.7 cells via HIF-mediated and MMP-mediated pathways, respectively. Silk sericin exerted like pro-oxidant effects and 4HR exerted anti-oxidant effects. Rats treated with a 4HR-incorporated silk mat showed higher levels of VEGF and angiogenin than those treated with a silk mat alone. [ABSTRACT FROM AUTHOR]

Abstract Manipulation of human T cell functioning by delivery of macromolecules such as DNA, RNA, or protein is limited, unless the human T cells have been stimulated or electropermeabilized. To achieve successful adaptation and survival of a grafted organ, the alloreactive T cells that induce graft rejection must be regulated. Corticosteroids, calcineurin inhibitors, and mTOR inhibitors, which are systemic immunosuppressants, are currently used for transplantation, with significant side effects. In this study, we demonstrated that a cell-permeable peptide (CPP), dNP2, could efficiently deliver proteins into human CD4 and CD8 T cells. We confirmed regulatory functioning of the cytoplasmic domain of CTLA-4 conjugated with dNP2 (dNP2-ctCTLA-4) in human T cell activation, proliferation, and chemokine receptor expression. We utilized a human skin allograft system in SCID/beige mice to examine whether dNP2-ctCTLA-4 could inhibit allograft rejection by controlling T cell responses. The grafted skin tissue inflammation, allogeneic T cell infiltration, and blood cytokine level was markedly reduced by dNP2-ctCTLA-4, resulting in successful transplantation. In addition, it also inhibited T cell alloresponses against microvessels formed form Bcl-2-transduced human umbilical vein endothelial cells implanted into Balb/c Rag1−/−/IL-2Rγ−/- double knockout (DKO) mice, assessed as reduced T cell infiltration and granzyme B expression. These results collectively suggest that dNP2 peptide conjugation offers a valuable tool for delivering macromolecules like proteins into human T cells, and dNP2-ctCTLA-4 is a novel agent that shows potential in controlling human T cell responses to allow successful adaptation of grafted tissues. [ABSTRACT FROM AUTHOR]

Abstract: Reverse electrodialysis (RED) is one of the promising sustainable technologies generating electric power from the mixing energy of two different salt solutions. Most of the reports on the RED systems are focused on scale‐up development and the improvement of maximum power density. However, regarding biocompatible and eco‐friendly natures, the RED system also has a great potential use where low electrical power is necessary, in particular for skin‐wearable biomedical devices. In this work, electronics‐free RED patches are devised as an ionic power source for active transdermal drug delivery. The electrodeless RED patches generate reliable voltages, which are proportional to the number of ion‐exchange membranes and salinity ratios, and successfully facilitate in vitro delivery of ionic drugs through mouse skin without involving any electronic component for the first time; 9, 20, and 36‐fold increases with lidocaine, ketorolac, and risedronate, respectively. Indeed, by using an osteoporosis‐induced mouse model, the RED patch delivery demonstrates powerful in vivo therapeutic effects against the diffusion‐based topical administration. The new ionic power source can allow transport of various types of drugs in the transdermal route and, more importantly, can be used for the operation of other portable biomedical devices. [ABSTRACT FROM AUTHOR]

Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates cellular responses such as proteasomal degradation and DNA repair upon interaction with its substrate. We identified a highly cationic region within the PAR-binding motif of Iduna; the region was similar among various species and showed amino acid sequence similarity with that of known cell-penetrating peptides (CPPs). We hypothesized that this Iduna-derived cationic sequence-rich peptide (Iduna) could penetrate the cell membrane and deliver macromolecules into cells. To test this hypothesis, we generated recombinant Iduna-conjugated enhanced green fluorescent protein (Iduna-EGFP) and its tandem-repeat form (d-Iduna-EGFP). Both Iduna-EGFP and d-Iduna-EGFP efficiently penetrated Jurkat cells, with the fluorescence signals increasing dose- and time-dependently. Tandem-repeats of Iduna and other CPPs enhanced intracellular protein delivery efficiency. The delivery mechanism involves lipid-raft-mediated endocytosis following heparan sulfate interaction; d-Iduna-EGFP was localized in the nucleus as well as the cytoplasm, and its residence time was much longer than that of other controls such as TAT and Hph-1. Moreover, following intravenous administration to C57/BL6 mice, d-Iduna-EGFP was efficiently taken up by various tissues, including the liver, spleen, and intestine suggesting that the cell-penetrating function of the human Iduna-derived peptide can be utilized for experimental and therapeutic delivery of macromolecules. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate (1) the effect of 4-hexylresorcinol (4HR) application on TNF-α expression in RAW264.7 cells and (2) the effect of 4HR ointment on burn wound healing in a rat burn wound model.Materials and Methods: RAW264.7 cells were cultured in the presence of different concentrations of 4HR, and the attached cells were sampled for western blot analysis at each time point. Animal studies were conducted on male Wistar rats (n=24). Three treatment groups were evaluated in this study: (1) treatment with ointment alone (negative control), (2) treatment with ointment containing 0.2wt% 4HR, and (3) treatment with ointment containing 2wt% 4HR. For the assessment of wound healing, digital photographs were taken at 1, 5, and 14 days. Animals were sacrificed at 1, 5, and 14 days for histological examination or ELISA analysis.Results: Western blot analysis showed that TNF-α protein levels were reduced following treatment with 4HR at concentrations between 1 and 10μg/mL. In animal studies, the average denuded area 14 days after burn was smaller in the 2wt% 4HR treatment group compared with the control group (P=0.022). Immunohistochemical analysis revealed lower TNF-α expression in the 2wt% 4HR treatment group compared with the control group 14 days after burn (P=0.027).Conclusion: 4HR reduced TNF-α expression in RAW264.7 cells and in the burn wounds of rats. Burn wounds dressed with ointment containing 4HR also exhibited rapid epithelization and collagen regeneration. [ABSTRACT FROM AUTHOR]

Cell-permeable peptides (CPPs) have been widely studied as an attractive drug delivery system to deliver therapeutic macromolecules such as DNA, RNA, and protein into cells. However, its clinical application is still limited and controversial due to the lack of a complete understanding of delivery efficiency in target cells. Previously we identified and characterized the novel and superior CPP, named dNP2, and here we comparatively analyzed intracellular delivery efficiency of dNP2 and TAT in various immune cells of mouse spleen to demonstrate their cell type preference. dNP2- or TAT-conjugated fluorescent proteins were most efficiently taken up by phagocytic cells such as dendritic cells and macrophages while little protein uptake was seen by lymphocytes including T cells, B cells, and NK cells. Interestingly CD8+ lymphoid dendritic cells and CD62LloCD44hi memory like T cell subsets showed significantly better uptake efficiency in vitro and in vivo relative to other dendritic cells or T cells, respectively. In addition, activated macrophages, T cells, and B cells took up the proteins more efficiently relative to when in the resting state. Importantly, only dNP2, not TAT, shows significant intracellular protein delivery efficiency in vivo. Collectively, this study provides important information regarding heterogeneous intracellular delivery efficiency of CPPs such as dNP2 and TAT with cell type preference in the spleen needed for its application in phagocytic cells or activated immune cells. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop novel biomedicated electrospun nanofibers for controlled release. Pre-formulation studies were carried out for nanofibers of sodium alginate (SA) (2 wt %)/polyvinyl alcohol (PVA) (10 wt %) composites (2/8, 3/7 and 4/6), by an electrospinning technique. The morphology and average diameter of the nanofibers were investigated by scanning electron microscopy (SEM). The optimum ratio (3/7) was used to load gatifloxacin hydrochloride (GH) (1wt %), found to form smooth fibers with uniform structures. The drug entrapment in the composite nanofibers was confirmed by SEM, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), and swelling behavior. The drug release behavior was investigated using phosphate-buffered saline (PBS) (pH 7.4) at 37°C for 24 h. The XRD and FTIR data demonstrate that there are good interactions between PVA and SA, possibly caused by hydrogen bonds. As much as 90% of the GH was released from the electrospun fibers within 6 h of incubation. Beyond this, the release was sustained for 24 h. The thickness of nanofibers greatly influenced the initial release and rate of drug release. Moreover, GH-loaded sodium alginate/PVA composite nanofibers exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound-healing applications. [ABSTRACT FROM AUTHOR]

Core binding factor β (Cbfβ) is a partner protein of Runx family transcription factors with minimally characterized function in cartilage. Here we address the role of Cbfβ in cartilage by generating chondrocyte-specific Cbfβ-deficient mice ( CbfbΔch/Δch) from Cbfb-floxed mice crossed with mice expressing Cre from the Col2a1 promoter. CbfbΔch/Δch mice died soon after birth and exhibited delayed endochondral bone formation, shorter appendicular skeleton length with increased proliferative chondrocytes, and nearly absent hypertrophic chondrocyte zones. Immunohistochemical and quantitative real-time PCR analyses showed that the number and size of proliferative chondrocytes increased and the expression of chondrocyte maturation markers at the growth plates, including Runx2, osterix, and osteopontin, significantly diminished in CbfbΔch/Δch mice compared to wild type mice. With regard to signaling pathways, both PTHrP-Ihh and BMP signaling were compromised in CbfbΔch/Δch mice. Mechanistically, Cbfβ deficiency in chondrocytes caused a decrease of protein levels of Runx transcription factors by accelerating polyubiquitination-mediated proteosomal degradation in vitro. Indeed, Runx2 and Runx3, but not Runx1, decreased in CbfbΔch/Δch mice. Collectively, these findings indicate that Cbfβ plays a critical role for chondrocyte differentiation through stabilizing Runx2 and Runx3 proteins in cartilage J. Cell. Physiol. 230: 162-171, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Hericium erinaceumis an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies ofH. erinaceumwas investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1–6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated β-galactosidase (SA-β-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases. [ABSTRACT FROM AUTHOR]

After palatal fusion, the dorsal and ventral epithelia of the palatal shelf differentiate into the nasal and oral mucosa, respectively. The tissue-specific differentiation of palatal epithelia along the dorsal-ventral axis is regulated by the signaling molecules expressed in the underlying mesenchyme. Thus, as in many other epithelial organs, differentiation relies on epithelial-mesenchymal interactions. To screen for region-specific mesenchymal signaling molecules that determine the fate of the palatal epithelia, we employed a laser microdissection (LMD) method. LMD allowed us to collect region-specific mesenchymal tissues at E13, prior to palatal fusion and the development of distinct dorsal and ventral epithelial morphology. Genome-wide screening was performed on the tissues collected using LMD to identify candidate mesenchymal signaling molecules. The microarray results were validated using real-time quantitative (qPCR) and in situ hybridization methods. The developmental role and interactions of the candidate genes were evaluated in in vitro-cultivated E13 palates using an anti-sense oligodeoxynucleotide (AS-ODN)-based loss-of-function approach. Apparent changes in the expression patterns of Runt-related transcription factor 2 ( Runx2) and LIM homeobox 8 ( Lhx8) were observed after knocking down each gene. Knock-down of Runx2 and Lhx8 also altered the immunolocalization pattern of cytokeratin18 (CK18), an established marker for nasal epithelium. These results were confirmed using Runx2 heterozygote mice. The mesenchymal signaling molecules Runx2 and Lhx8, which possess region-specific expression patterns along the dorsoventral axis, functionally interact to regulate the cellular and molecular characteristics of dorsal and ventral epithelia, suggesting that mesenchymal signaling molecules determine the dorsoventral fate of epithelial structures in the developing palate. [ABSTRACT FROM AUTHOR]

Piceatannol, a metabolite of resveratrol found in red wine and grapes, displays a wide spectrum of biological activity. Although the anti-oxidant, anti-inflammatory, and anti-tumorigenesis activity of piceatannol has been extensively studied, its role in the adaptive immune response has received less attention. Here we investigated the role of piceatannol, a well-known Syk inhibitor, in T cell activation, proliferation, and differentiation using isolated murine splenic T cells from C57BL/6 mice. Piceatannol treatment inhibited surface expression of CD4 and CD8 T cell activation markers CD25 and CD69, reduced production of cytokines IFNγ, IL-2, and IL-17, and suppressed proliferation of activated T cells. Moreover, piceatannol treatment significantly inhibited differentiation of CD4 + CD25 − CD62L + naïve CD4 T cells into Th1, Th2, and Th17 cells, presumably due to inhibition of TcR signaling through p-Erk, p-Akt, and p-p38. Piceatannol appears to be a useful nutritional or pharmacological biomolecule that regulates effector T cell functions such as cytokine production, differentiation, and proliferation. [ABSTRACT FROM AUTHOR]