Novel conformation of hyaluronic acid with improved cosmetic efficacy.

BACKGROUND: Hyaluronic acid presents a valuable cosmetic ingredient that occurs naturally. Its direct links to skin aging has led to its broad application. The aim of this study was to improve the cosmetic efficacy of high molecular weight hyaluronic acid (HMWHA) without chemical modifications and evaluate such improvements through clinical and in vitro studies. METHODS: A novel formulation of HMWHA (SCAI-HA) was prepared and investigated to comparatively assess 6 clinical and 2 in vitro parameters concerning its dermatological cosmetic efficacy and biological properties. The dermatological and cellular parameters examined in this study include skin hydration, transepidermal water loss (TEWL), skin elasticity, wrinkles, facial sagging, dermal density, cytotoxicity, and collagen synthesis. RESULTS: SCAI-HA exhibited the ability to improve the tested dermatological parameters (hydration, elasticity, wrinkles, and density) to magnitudes comparable to those of HMWHA. In addition, SCAI-HA showed notably improved capacities for attenuating facial sagging and TEWL and promoting cellular collagen synthesis in normal human dermal fibroblasts. CONCLUSION: SCAI-HA presents a novel conformation of HMWHA with improved cosmetic efficacy in mitigating (i) facial sagging, (ii) TEWL, and promoting, and (iii) collagen synthesis. These findings denote the enhancement of SCAI-HA as a cosmetic ingredient with potential anti-aging properties.

Parylene-Coated Polytetrafluoroethylene-Membrane-Based Portable Urea Sensor for Real-Time Monitoring of Urea in Peritoneal Dialysate.

A portable urea sensor for use in fast flow conditions was fabricated using porous polytetrafluoroethylene (PTFE) membranes coated with amine-functionalized parylene, parylene-A, by vapor deposition. The urea-hydrolyzing enzyme urease was immobilized on the parylene-A-coated PTFE membranes using glutaraldehyde. The urease-immobilized membranes were assembled in a polydimethylsiloxane (PDMS) fluidic chamber, and a screen-printed carbon three-electrode system was used for electrochemical measurements. The success of urease immobilization was confirmed using scanning electron microscopy, and fourier-transform infrared spectroscopy. The optimum concentration of urease for immobilization on the parylene-A-coated PTFE membranes was determined to be 48 mg/mL, and the optimum number of membranes in the PDMS chamber was found to be eight. Using these optimized conditions, we fabricated the urea biosensor and monitored urea samples under various flow rates ranging from 0.5 to 10 mL/min in the flow condition using chronoamperometry. To test the applicability of the sensor for physiological samples, we used it for monitoring urea concentration in the waste peritoneal dialysate of a patient with chronic renal failure, at a flow rate of 0.5 mL/min. This developed urea biosensor is considered applicable for (portable) applications, such as artificial kidney systems and portable dialysis systems.

Neutrophils dominate the immune cell composition in non-small cell lung cancer.

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Unfortunately, these trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Here, we use a flow cytometry panel capable of measuring 51 immune cell populations to comprehensively identify the immune cell composition and function in NSCLC. The results show that the immune cell composition is fundamentally different in lung adenocarcinoma as compared with lung squamous cell carcinoma, and that neutrophils are the most prevalent immune cell type. Using T-cell receptor-ß sequencing and tumour reactivity assays, we predict that tumour reactive T cells are frequently present in NSCLC. These results should help to guide the design of clinical trials and the direction of future research in this area.

Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma.

Insulin receptor substrate-1 (IRS-1) is a signaling adaptor protein that interfaces with many pathways activated in lung cancer. It has been assumed that IRS-1 promotes tumor growth through its ability to activate PI3K signaling downstream of the insulin-like growth factor receptor. Surprisingly, tumors with reduced IRS-1 staining in a human lung adenocarcinoma tissue microarray displayed a significant survival disadvantage, especially within the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant subgroup. Accordingly, adenoviral Cre recombinase (AdCre)-treated LSL-Kras/Irs-1(fl/fl) (Kras/Irs-1(-/-)) mice displayed increased tumor burden and mortality compared with controls. Mechanistically, IRS-1 deficiency promotes Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling via the IL-22 receptor, resulting in enhanced tumor-promoting inflammation. Treatment of Kras/Irs-1(+/+) and Kras/Irs-1(-/-) mice with JAK inhibitors significantly reduced tumor burden, most notably in the IRS-1-deficient group.

Effect of low-dosage electron beam irradiation on antioxidant activities of navel oranges during storage at a low temperature of 3°C.

Effects of low-dosage electron beam irradiation on antioxidant activities of Navel oranges during storage at a low temperature of 3°C were studied. Oranges were irradiated at dosages of 0.2, 0.4, 0.6, 0.8, and 1.0 kGy and changes in antioxidant compounds and antioxidant activities were investigated. No changes in total phenolic contents or flavonoid contents were observed with an increase in radiation dosage. Also, no differences between non-irradiated and irradiated oranges in DPPH radical scavenging and ABTS radical scavenging activities, FRAP values, and reducing powers were observed. Electron beam irradiation at dosages less than 1 kGy does not affect levels of antioxidant compounds and antioxidant activities of Navel oranges.

Neutrophil elastase promotes myofibroblast differentiation in lung fibrosis.

IPF is a progressive lung disorder characterized by fibroblast proliferation and myofibroblast differentiation. Although neutrophil accumulation within IPF lungs has been negatively correlated with outcomes, the role played by neutrophils in lung fibrosis remains poorly understood. We have demonstrated previously that NE promotes lung cancer cell proliferation and hypothesized that it may have a similar effect on fibroblasts. In the current study, we show that NE(-/-) mice are protected from asbestos-induced lung fibrosis. NE(-/-) mice displayed reduced fibroblast and myofibroblast content when compared with controls. NE directly both lung fibroblast proliferation and myofibroblast differentiation in vitro, as evidenced by proliferation assays, collagen gel contractility assays, and αSMA induction. Furthermore, αSMA induction occurs in a TGF-ß-independent fashion. Treatment of asbestos-recipient mice with ONO-5046, a synthetic NE antagonist, reduced hydroxyproline content. Thus, the current study points to a key role for neutrophils and NE in the progression of lung fibrosis. Lastly, the study lends rationale to use of NE-inhibitory approaches as a novel therapeutic strategy for patients with lung fibrosis.

Plasticity of airway epithelial cell transcriptome in response to flagellin.

Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium.

Physicochemical and Sensory Properties of Appenzeller Cheese Supplemented with Shrimp Powder.

The effects of adding shrimp (Periclimenes imperator) powder to Appenzeller cheese on quality and characteristics during ripening were investigated. Cheese samples were prepared containing 1.0%, 2.0%, and 3.0% shrimp powder. Changes in the lactic acid bacterial populations, pH, water-soluble nitrogen concentrations, consumer acceptability, colour and texture were monitored during ripening. The addition of shrimp powder did not affect the appearance or consumer sensory characteristics of the cheeses. Likewise, cheese cohesiveness, fracturability, and springiness were not significantly altered. It was concluded that the quality of the Appenzeller cheese was not affected by adding shrimp powder.

Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors.

A series of new 2-(2-aminopyrimidin-4-yl)phenol derivatives were synthesized as potential antitumor compounds. Substitution with pyrrolidine-3,4-diol at the 4-position of phenol provided potent inhibitory activity against CDK1 and CDK2. X-ray crystal structural studies were performed to account for the effect of the substituent on both the enzymatic and cell growth inhibitory activities.

Transition of stable isotope ratios of leaf water under simulated dew formation.

Dew formation, a common meteorological phenomenon, is expected to intensify in the future. Dew can influence the H2¹8O and HDO isotopic compositions of leaf water (δ(L) ), but the phenomenon has been neglected in many experimental and modelling studies. In this study, the dew effect on δ(L) was investigated with a dark plant chamber in which dew formation was introduced. The H2¹8O and HDO compositions of water vapour, dew water and leaf water of five species were measured for up to 48 h of dew exposure. Our results show that the exchanges of H2¹8O and HDO in leaf water with the air continued in the darkness when the net H2¹6O flux was zero. Our estimates of the leaf conductance using the isotopic mass balance method ranged from 0.035 to 0.087 mol m⁻² s⁻¹, in broad agreement of the night-time stomatal conductance reported in the literature. In our experiments, the conductance of the C3 species was 0.04 ± 0.01 mol m⁻² s⁻¹ and that of the C3 plants was 0.10 ± 0.04 mol m⁻² s⁻¹. At the end of 16 h dew exposure, 72 (±17) and 94 (±11)% of the leaf water came from dew according to the ¹8O and D tracer, respectively.

Antioxidative and antiviral properties of flowering cherry fruits (Prunus serrulata L. var. spontanea).

The phenolic compounds of many fruits have been known to be efficient cellular protective antioxidants. In this study, antioxidative and antiviral properties of flowering cherry cultivars (Prunus yedoensis, Prunus sargentii, Prunus lannesiana, and Prunus cerasus) in Korea were investigated. The antioxidant property was assayed for specific activities including 2,2-diphenyl-1-picrylhydrazyl (DPPH) hydroxy radical scavenging activity, reducing power capacity, and superoxide dismutase (SOD) like activity. In addition, antiviral activity was determined by inhibition studies on the infection cycle of porcine epidemic diarrhea virus (PEDV), measured as minimum concentration of cherry extracts that inhibited 50% of cytopathic effect (CPE) on PEDV. Our results show that the four varieties of cherries contain substantially high antioxidants and antiviral activities. In particular, P. cerasus contains higher antioxidants and antiviral activities as well as polyphenolic content than other varieties. Our data indicate that Korean native cherry cultivars could be beneficial supplements of dietary antioxidants and natural antiviral agents.

[Evaluation of the efficacies of rapid antigen test, multiplex PCR, and real-time PCR for the detection of a novel influenza A (H1N1) virus].

BACKGROUND: In April 2009, a novel influenza A (H1N1) virus was detected in the US, and at the time of conducting this study, H1N1 infection had reached pandemic proportions. In Korea, rapid antigen tests and PCR assays have been developed to detect the H1N1 virus. We evaluated the efficacies of rapid antigen test, multiplex PCR, and real-time PCR for detecting the H1N1 virus. METHODS: From August to September 2009, we tested 734 samples obtained from nasopharyngeal swab or nasal swab using rapid antigen test (SD Influenza Antigen, Standard Diagnostics, Inc., Korea) and multiplex PCR (Seeplex FluA ACE Subtyping, Seegene, Korea). We also tested 224 samples using the AdvanSure real-time PCR (LG Life Sciences, Korea) to compare the results obtained using real-time PCR with those obtained using multiplex PCR. Furthermore, 99 samples were tested using the AdvanSure real-time PCR and the AccuPower real-time PCR (Bioneer, Korea). RESULTS: In comparison with the results of multiplex PCR, the sensitivity and specificity of the rapid antigen test were 48.0% and 99.8%, respectively. The concordance rate for multiplex PCR and the AdvanSure real-time PCR was 99.6% (kappa=0.991, P=0.000), and that for the AdvanSure real-time PCR and the AccuPower real-time PCR was 97.0% (kappa=0.936, P=0.000). CONCLUSIONS: The rapid antigen test is significantly less sensitive than PCR assay; therefore, it is not useful for H1N1 detection; however multiplex PCR, the AdvanSure real-time PCR, and the Accu-Power real-time PCR can be useful for H1N1 detection.

The two-dimensional thio-phosphate CsCrP(2)S(7).

The quaternary title compound, caesium chromium(III) hepta-thio-diphosphate(V), CsCrP(2)S(7), has been synthesized using the reactive halide flux method. It is isotypic with other AMP(2)S(7) (A = alkali metal; M = Cr, V or In) structures and consists of two-dimensional (∞) (2)[CrP(2)S(7)](-) layers extending parallel to (001) which are separated from each other by Cs(+) ions (symmetry 2). The layer is built up from slightly distorted octa-hedral [CrS(6)] units (symmetry 2) and bent [P(2)S(7)] units consisting of two corner-sharing [PS(4)] tetra-hedra. The [CrS(6)] octa-hedra share two edges and two corners with the [PS(4)] tetra-hedra. There are only van der Waals inter-actions present between the layers. The Cs(+) ions are located in this van der Waals gap and stabilize the structure through weak ionic inter-actions. The classical charge balance of the title compound can be expressed as [Cs(+)][Cr(3+)][P(5+)](2)[S(2-)](7.).

deltaO of water vapour, evapotranspiration and the sites of leaf water evaporation in a soybean canopy.

Stable isotopes in water have the potential to diagnose changes in the earth's hydrological budget in response to climate change and land use change. However, there have been few measurements in the vapour phase. Here, we present high-frequency measurements of oxygen isotopic compositions of water vapour (delta(v)) and evapotranspiration (delta(ET)) above a soybean canopy using the tunable diode laser (TDL) technique for the entire 2006 growing season in Minnesota, USA. We observed a large variability in surface delta(v) from the daily to the seasonal timescales, largely explained by Rayleigh processes, but also influenced by vertical atmospheric mixing, local evapotranspiration (ET) and dew formation. We used delta(ET) measurements to calculate the isotopic composition at the sites of evaporative enrichment in leaves (delta(L,e)) and compared that with the commonly used steady-state prediction (delta(L,s)). There was generally a good agreement averaged over the season, but larger differences on individual days. We also found that vertical variability in relative humidity and temperature associated with canopy structure must be addressed in canopy-scale leaf water models. Finally, we explored this data set for direct evidence of the Péclet effect.

Tissue inhibitor of metalloproteinase-1 moderates airway re-epithelialization by regulating matrilysin activity.

Obliterative bronchiolitis (OB) is the histopathological finding in chronic lung allograft rejection. Mounting evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue inhibitor of metalloproteinase (TIMP)-1 expression increases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallproteinase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization through matrilysin. We found that TIMP-1 and matrilysin co-localized in the epithelium of human lungs with OB and both co-localized and co-immunoprecipitated in wounded primary airway epithelial cultures. TIMP-1-deficient cultures migrated faster, and epithelial cells spread to a greater extent compared with wild-type cultures. TIMP-1 also inhibited matrilysin-mediated cell migration and spreading in vitro. In vivo, TIMP-1 deficiency enhanced airway re-epithelialization after naphthalene injury. Furthermore, TIMP-1 and matrilysin co-localized in airway epithelial cells adjacent to the wound edge. Our data demonstrate that TIMP-1 interacts with matrix metalloproteinases and regulates matrilysin activity during airway epithelial repair. Furthermore, we speculate that TIMP-1 overexpression restricts airway re-epithelialization by inhibiting matrilysin activity, contributing to a stereotypic injury response that promotes airway fibrosis via bronchiole airway epithelial damage and obliteration.

Synthesis and biological evaluation of 3,5-diaminoindazoles as cyclin-dependent kinase inhibitors.

A novel series of 3,5-diaminoindazoles were prepared and found to be CDK inhibitors. Potent inhibitors against CDK1 and CDK2 were obtained by introduction of 1lambda(6)-isothiazolidine-1,1-dioxide at 5-position of indazole. Anti-proliferative activities of compounds were evaluated using EJ, HCT116, SW620, and A549 cancer cell lines.

Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl ketones.

Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.

Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists.

Oxime ethers of alpha-acyl-beta-phenylpropanoic acids were prepared to apply as PPARalpha and gamma dual agonists. Among them, compound 11l proved to exhibit potent in vitro activities with EC(50) of 19 and 13nM in PPARalpha and gamma, respectively. It showed better glucose lowering effects than rosiglitazone 1 and ameliorated the lipid profile like plasma triglyceride in db/db mice model.

3-Hydroxychromones as cyclin-dependent kinase inhibitors: synthesis and biological evaluation.

A novel series of 3-hydroxychromones were prepared and found to be CDK inhibitors. Isothiazolidine 1,1-dioxide analogues showed potent CDK1 and CDK2 inhibitory activities and inhibited proliferation of EJ, HCT116, SW620, and MDAMB468 cancer cells.