Search

Background Various graft materials have been used to repair nasoseptal perforation, but there is no standardized treatment method. The anterior maxillary sinus wall is flattened in appearance and can be easily obtained in a sufficient amount for a large-sized nasoseptal perforation. Objectives The aim of this study is to determine whether the anterior maxillary sinus wall is suitable as an interpositional graft in the surgical repair of septal or nasoseptal perforation. Methods This is a retrospective review of 21 patients who underwent repair of nasoseptal perforation using anterior maxillary sinus wall as an interpositional graft. The etiology, pre- and post-operative NOSE and GBI score, and perforation size were reviewed. The surgical outcome was considered successful if total closure was achieved after postoperative follow-up. Results 19 of the 21 perforations were successfully repaired with anterior maxillary sinus wall. Failure of the repair was found in 2 patients. Causal etiology of perforation was previous septoplasty in 10 patients, and electrocautery in 1 case, but not identified in 10 cases. The largest size was 2.7 × 2.2 cm. The most common symptoms were epistaxis, crusting, and nasal obstruction. Closure of septal perforation resulted in improved subjective symptoms and quality of life which were evaluated with NOSE and GBI score. Conclusion Anterior maxillary sinus wall as interpositional graft between mucoperichondrial flaps can be used to reliably repair nasoseptal perforations.

Objective To systematically translate the Fugl-Meyer Assessment (FMA) into a Korean version of the FMA (K-FMA).Methods We translated the original FMA into the Korean version with three translators and a translation committee, which included physiatrists, physical therapists, and occupational therapists. Based on a test-retest method, each of 31 patients with stroke was assessed by two evaluators twice, once on recruitment, and again after a week. Analysis of intra- and inter-rater reliabilities was performed using the intra-class correlation coefficient, whereas validity was analysed using Pearson correlation test along with the Motricity Index (MI), Motor Assessment Scale (MAS), and Berg Balance Scale (BBS).Results The intra- and inter-rater reliabilities were significant for the total score, and good to excellent reliability was noted in all domains except for the joint range of motion of the lower extremity domain of the K-FMA. The MI and MAS scores were significantly correlated with all domains, all with p

Background Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). Methods SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. Results The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. Conclusions Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies. Electronic supplementary material The online version of this article (10.1007/s40259-019-00402-0) contains supplementary material, which is available to authorized users.

Background Little is known about the role of lymphotoxins (LTs) family in the sinonasal mucosa of patients with chronic rhinosinusitis (CRS). This study aims at investigating the expression of LIGHT, LTα, LTβ, and their receptors, LTβR and HVEM in normal and inflammatory sinus mucosa, and the effect of LIGHT and LTalpha1beta2 on chemokine secretion in epithelial cells, epithelial permeability, and leukocyte migration. Material and methods The expression of LTs family in sinonasal mucosa was evaluated with real-time PCR, immunohistochemistry, and western blot. In LTβR, HVEM siRNA, or control siRNA-transfected epithelial cells treated with LIGHT or LTalpha1beta2, the expression of chemokines, the epithelial permeability, and the expression of junctional complex proteins were evaluated using real-time PCR, ELISA, western blot, confocal microscopy, and FITC-dextran. In cultured endothelial cells treated with LIGHT or LTalpha1beta2, the expression of ICAM-1 and VCAM-1, and leukocyte migration were elucidated. Results LTs family was expressed in normal mucosa and their levels were increased in inflammatory mucosa of CRS patients. Recombinant LIGHT and LTalpha1beta2 induced chemokine secretion, increased epithelial permeability, and promoted leukocyte migration. However, the activity of LIGHT and LTalpha1beta2 was attenuated in cells transfected with LTβR and HVEM siRNA. Conclusions LIGHT and LTs may participate in the ongoing process of chronic inflammation, inducing chemokine secretion, leukocyte migration, and dysregulated epithelial barrier through LTβR and HVEM in sinonasal mucosa.

Background Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS). Objective We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone. Methods The presence of NETs in nasal secretion and the release of NETs from neutrophils stimulated with macrolides or dexamethasone were evaluated by dsDNA Assay kit and fluorescence microscope. The chemokine secretion, epithelial permeability, and transendothelial leucocyte migration were measured in cultured cells incubated with NETs, the supernatant of unstimulated neutrophils (unstim), NETs inhibitor (DPI), or H3Cit, where the expression of junctional complex proteins and ICAM-1 was evaluated by real-time PCR, Western blots, and confocal microscope. Results The amount of NETs and NETs-forming neutrophils in nasal secretion increased in exacerbated CRS. Epithelial cells treated with NETs or H3Cit secreted chemokines and showed decreased permeability associated with up-regulated junctional complex proteins. Increased transendothelial leucocyte migration associated with up-regulated ICAM-1 was noted in endothelial cells treated with NETs or H3Cit. These findings were not found in cells treated with unstim, or DPI. NETs were released by macrolides, but not by dexamethasone. Conclusions and clinical relevance NETs formation increased in exacerbated CRS, inducing chemokine secretion, strengthening the epithelial barrier, and promoting the neutrophils infiltration. Therefore, the release of NETs in CRS might be beneficial or detrimental to CRS patients.

Objective Osteoarthritis (OA) patients who undergo staged bilateral total knee arthroplasty (TKA) feel postoperative hyperalgesia in the second operated knee compared with the first knee. Ketamine is an important drug for central temporal summation and inhibition of secondary mechanical hyperalgesia. This study investigated whether central sensitization has a significant effect on hyperalgesia after consecutive operations. Methods Seventy-one of 80 OA patients were randomly allocated to the ketamine or saline group. A bolus of ketamine (group K) or saline (group C) (0.5 mg/kg) was injected before induction and at an infusion rate of 3 µg/kg/minute during surgery. A visual analog scale (VAS) was used to assess resting and moving pain and opioid consumption on postoperative days 1, 2, and 3. Results The difference in the VAS score between stages 1 and 2 (DV2-V1) was higher in the ketamine compared with the saline group. DV2-V1 for movement between the two groups was not inferior for all periods. Ketamine did not show a large analgesic effect on second-operated knee hyperalgesia in staged bilateral TKAs. Conclusions We could not confirm that hyperalgesia was only related to central sensitization with low-dose ketamine. Other factors might be also associated with the hyperexcitability of nociceptive stimuli. Clinical Research Information Service (CRIS) trial registry no: KCT0001481

In this study, to examine the application of cast-in-place of high-flowable and high-strength concrete, an experimental study on the lateral pressure of a formwork was preformed. The experiment specimens, which have different casting height and casting speed were prepared. The lateral pressure and the change of temperature from test specimens were obtained. The maximum lateral pressure was shown to lateral pressure of fresh concrete. Immediately after placing, the lateral pressure starts to decrease and, after 12 hours, it showed a stabilization. The decreased tend of the lateral pressure was similar with normal-strength concrete, which appears stabilization after 3~4 hours from casting completion. The more casting speed is fast, the more maximum lateral pressure is high, but pressure reduction with the lapse of time was nearly similar. In addition, it was found that there was no direct relation between the hydration heat and the lateral pressure reduction.

We report that engineered Cas9 variants with improved specificity—eCas9-1.1 and Cas9-HF1—are often poorly active in human cells, when complexed with single guide RNAs (sgRNAs) with a mismatch at the 5’ terminus, relative to target DNA sequences. Because the nucleotide at the 5’ end of sgRNAs, expressed under the control of the commonly-used U6 promoter, is fixed to a guanine, these attenuated Cas9 variants are not useful at many target sites. By using sgRNAs with matched 5’ nucleotides, produced by linking them to a self-cleaving ribozyme, the editing activity of Cas9 variants can be rescued without sacrificing high specificity. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1355-3) contains supplementary material, which is available to authorized users.

The seabird plays an important role as one of the indicator species for the status of and changes within marine ecosystems. Therefore, the conservation of seabirds and their habitats is important for maintaining the structure and function of marine ecosystems. Biological invasions affect most ecosystems on oceanic islands. In particular, Rattus spp. is the invasive species with the greatest impact on the seabird population. Introduced predators, like rats, severely affect seabirds and endanger them worldwide. The breeding population of Streaked Shearwaters Calonectris leucomelas in Sasu Island is one of biggest seabird colonies in Korea, and the Norway Rat Rattus norvegicus is known as an alien predator in this island. In this study we investigated rates of burrow occupancy and breeding success of Streaked Shearwaters for 7 years, and the impact of Norway Rats on the breeding success of Streaked Shearwaters breeding in Sasu Island for 4 years. Our results show that the percentage of breeding burrows decreased according to breeding stage during several years in the monitoring period, and that predation by the Norway Rat was the main cause in hatching failures. Consequently, although our results indicate that their breeding population is not likely to decline, Norway Rats have been affecting the breeding status of Streaked Shearwaters on Sasu Island during the last decade.

Background Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS). Objective we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists. Methods The presence of virus in the sinonasal mucosa was evaluated with real-time PCR. The expression of interferons and ISGs in the sinonasal mucosa and in cultured epithelial cells treated with TH1 and TH2 cytokines, macrolides, dexamethasone, or TLR3 and TLR7 agonists were evaluated with real-time PCR and Western blotting. The expression of TLR3 and TLR7 in the sinonasal mucosa were evaluated with immunohistochemistry. Results Respiratory viruses were detected in 15% of samples. Interferons and ISGs are expressed in normal mucosa, but their levels were decreased in patients with CRS. Interferon and ISG levels were upregulated in cells treated with macrolides, dexamethasone, or TLR3 agonist, but some were decreased in cytokine-treated cells. TLR3 and TLR7 levels showed no significant difference between normal and inflammatory sinus mucosal tissue. Conclusion These results suggest that decreased levels of interferons and ISGs in patients with CRS might contribute to impairment of the antiviral innate response in inflammatory sinonasal epithelial cells. Macrolides and glucocorticoids might provide positive effects on the treatment of CRS by upregulating interferon and ISG expression., Graphical abstract

Sirtuin1 (SIRT1), a protein/histone deacetylase, protects against the development of pulmonary emphysema. However, the molecular mechanisms underlying this observation remain elusive. The imbalance of tissue inhibitor of matrix metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. We hypothesized that SIRT1 protects against emphysema by redressing the imbalance between MMPs and TIMPs. To test this hypothesis, SIRT1-deficient and overexpressing/transgenic mice were exposed to cigarette smoke (CS). The protein level and activity of MMP-9 were increased in lungs of SIRT1-deficient mice exposed to CS compared with wild-type (WT) littermates, and these effects were attenuated by SIRT1 overexpression. SIRT1 deficiency decreased the level of TIMP-1, which was augmented in SIRT1 transgenic mice compared with WT littermates by CS. However, the level of MMP-2, MMP-12, TIMP-2, TIMP-3, or TIMP-4 was not altered by SIRT1 in response to CS exposure. SIRT1 reduction was associated with imbalance of TIMP-1 and MMP-9 in lungs of smokers and COPD patients. Mass spectrometry and immunoprecipitation analyses revealed that TIMP-1 acetylation on specific lysine residues was increased, whereas its interaction with SIRT1 and MMP-9 was reduced in mouse lungs with emphysema, as well as in lungs of smokers and COPD patients. SIRT1 deficiency increased CS-induced TIMP-1 acetylation, and these effects were attenuated by SIRT1 overexpression. These results suggest that SIRT1 protects against COPD/emphysema, in part, via redressing the TIMP-1/MMP-9 imbalance involving TIMP-1 deacetylation. Thus redressing the TIMP-1/MMP-9 imbalance by pharmacological activation of SIRT1 is an attractive approach in the intervention of COPD.

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway.

Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD+-dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown. Here, we showed increased cellular senescence in lungs of COPD patients. SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice. Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance. These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes. Inhibition of lung inflammation by an NF-κB/IKK2 inhibitor did not have any beneficial effect on emphysema. Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation. Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema.

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggestmore » that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

Extracellular superoxide dismutase (ECSOD or SOD3) is highly expressed in lungs and functions as a scavenger of O 2 • ─ . ECM fragmentation, which can be triggered by oxidative stress, participates in the pathogenesis of chronic obstructive pulmonary disease (COPD) through attracting inflammatory cells into the lungs. The level of SOD3 is significantly decreased in lungs of patients with COPD. However, the role of endogenous SOD3 in the development/progression of emphysema is unknown. We hypothesized that SOD3 protects against emphysema by attenuating oxidative fragmentation of ECM in mice. To test this hypothesis, SOD3-deficient, SOD3-transgenic, and WT C57BL/6J mice were exposed to cigarette smoke (CS) for 3 d (300 mg total particulate matter/m 3 ) to 6 mo (100 mg/m 3 total particulate matter) or by intratracheal elastase injection. Airspace enlargement, lung inflammation, lung mechanical properties, and exercise tolerance were determined at different time points during CS exposure or after elastase administration. CS exposure and elastase administration caused airspace enlargement as well as impaired lung function and exercise capacity in SOD3-null mice, which were improved in mice overexpressing SOD3 and by pharmacological SOD mimetic. These phenomena were associated with SOD3-mediated protection against oxidative fragmentation of ECM, such as heparin sulfate and elastin, thereby attenuating lung inflammatory response. In conclusion, SOD3 attenuates emphysema and reduces oxidative fragmentation of ECM in mouse lung. Thus, pharmacological augmentation of SOD3 in the lung may have a therapeutic potential in the intervention of COPD/emphysema.

Rationale IκB kinase (IKK) activates NF-κB which plays a pivotal role in pro-inflammatory response in the lung. NF-κB has been shown to be activated in alveolar macrophages and peripheral lungs of smokers and patients with chronic obstructive pulmonary disease. We investigated the anti-inflammatory effect of a highly selective and novel IKKβ/IKK2 inhibitor, PHA-408 [8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo[γ]indazole-3-carboxamide], in lungs of rat in vivo . Methods Adult Sprague-Dawley rats were administered orally with PHA-408 (15 and 45 mg/kg) daily for 3 days and exposed to LPS aerosol (once on day 3, 2 h post-last PHA-408 administration) or cigarette smoke (CS; 2 h after PHA-408 administration for 3 days). Animals were sacrificed at 1, 4 and 24 h after the last exposure, and lung inflammatory response and NF-κB activation were measured. Results Oral administration of IKKβ/IKK2 inhibitor PHA-408 significantly inhibited LPS- and CS-mediated neutrophil influx in bronchoalveolar lavage (BAL) fluid of rats. The levels of pro-inflammatory mediators in BAL fluid (CINC-1) and lungs (IL-6, TNF-α, IL-1β and GM-CSF) were also reduced by PHA-408 administration in response to LPS or CS exposures. The reduced pro-inflammatory response in PHA-408-administered rats was associated with decreased nuclear translocation and DNA binding activity of NF-κB in response to LPS or CS. Conclusion These results suggest that IKKβ/IKK2 inhibitor PHA-408 is a powerful anti-inflammatory agent against LPS- and CS-mediated lung inflammation.

A novel biofilter with an agitator to control excessive biomass accumulation, the agitating biotrickling filter (ABTF) system, was developed for treatment of gaseous styrene using Brevibacillus sp. as the sole microorganism the ABTF exhibited an elimination capacity of 3 kg styrene m(-3) day(-1). After 110 days, the biodegradation efficiency decreased because of the clogging. The excess biomass was effectively removed by agitation. After the first agitation step, 42.4 g biomass was eliminated, and the removal efficiency increased from 60% to 95%. Stable operation of the ABTF was achieved by controlling the biomass accumulation via the agitation of the filter bed.

Sulforaphane is an antioxidant and a potent stimulator of natural detoxifying enzyme and associated with lowered risk of cancer that is associated with the consumption of cruciferous vegetables. The chemopreventive effects of SFN was investigated using the MCF-7 human breast cancer cells and the M13SV1-immortalized human breast luminal epithelial cells. Sulforaphane reduced proliferation in MCF-7 cells and inhibited cyclooxygenase-2 expression in M13SV1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). The chemopreventive effects of sulforaphane were associated with p38 mitogen-activated protein kinase suggest its important role in cell survival/apoptosis regulation and stabilization of cyclooxygenase-2. Sulforaphane upregulates p38 in MCF-7 cells and prevented TPA-reduced phosphorylation of p38 in M13SV1 cells, but activated caspase-7 associated with apoptosis in MCF-7 cells. These results suggest that sulforaphane may be an alternative candidate for targeted prevention of ER-positive and cyclooxygenase-2-induced phenotypes and breast cancer.

Oligonol is a novel catechin-rich biotechnology product. The role of oligonol in modulating intracellular signaling mechanisms was investigated with the view of demonstrating its potential chemopreventive effect and the ability to inhibit cell proliferation using the estrogen-responsive MCF-7 and the estrogen-unresponsive MDA-MB-231 human breast cancer cell lines. Cell survival assay indicated that Oligonol was cytotoxic to both cells. Oligonol triggered apoptosis as revealed by the morphological features typical of nucleus staining and the accumulation of sub-G1 peak. Treatment with 25 microg/ml Oligonol resulted in an activation of caspase-7 and up-regulation of Bad on MCF-7 cells, while the Oligonol (20 microg/ml) induced up-regulation of Bcl-2 protein in a time-response manner on MDA-MB-231 cells. ERK1/2 in both cells were inactivated after Oligonol treatment in a time-dependent manner, and also inactivated upstream MEK1/2. Oligonol triggers apoptosis in MCF-7 and MDA-MB-231 cells through the modulation of pro-apoptotic Bcl-2 family proteins and MEK/ERK signaling pathway.

Composts are often employed as a packing material of a biofilter for treating gaseous streams contaminated with volatile organic compounds or malodorous chemicals. In order to select a good packing material for a biofilter, two commercially available composts in Korea, pig manure compost (PMC) and food waste compost (FWC), were studied during the treatment of gaseous p -xylene. The composts were used as purchased or after washed with water to remove water-soluble nutrients and microorganisms on the compost surface. Washed composts exhibited a shorter start-up period for a biofilter to reach a high and steady degradation level of p -xylene. Nitrogen limitation was experienced when a biofilter was operated without adding a supplemental nitrogen source. The soluble nitrogen content was initially higher in PMC than in FWC, but the latter had a higher content of insoluble nitrogen and a lower activity of the nitrification which converts NH 3 -N to NO 3 -N. The biofilter packed with FWC yielded a lower loss of nitrogen as leachate and exhibited a more stable performance for a longer period of 150 days with the maximal elimination capacity of 21 g p -xylene m −3 h −1 .

Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase.

Much of the interest on the chemopreventive properties of licorice has been focused on the plant genius Glycyrrhiza glabra. In this study the ethanol extract of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was investigated for its estrogenic effect and the ability to inhibit cell proliferation in the MCF-7 human breast cancer cell line. The extract of the root of G. uralensis was fractionated in EtOH:H(2)O (80:20) (80% ethanol). The extract exhibited estrogenic effects similar to 17beta- estradiol (E2) and induced apoptosis at the same dose level (100 microg/ml) in MCF-7 breast cancer cells, results were associated with up-regulation of tumor suppressor gene p53 and pro-apoptotic protein Bax. G. uralensis extract caused the up-regulation of p21(waf1/cip1) and down-regulation of cdk 2 and cyclin E and most significantly, induced G1 cell cycle arrest. This is the first study to show that the ethanolic extract of the root of G. uralensis has an estrogen-like activity and anti-cancer effects against MCF-7 human breast cancer cells. Whilst the use of phytoestrogens to protect against hormone-dependent cancers or as a 'natural' alternative to hormone replacement therapy remains controversial, the data in this paper support the suggestion that extracts of root of the Chinese licorice G. uralensis might be of importance in this debate.

Gene mining of the genome database of the zebra fish Danio rerio revealed the presence of a putative microsomal epoxide hydrolase (mEH)-like protein containing the characteristic catalytic triad composed of Asp 223 , Glu 402 , and His 429 as well as the oxyanion hole common to all mEH. Based on the sequence information, a new EH gene was cloned by PCR amplification of cDNA of the zebra fish Danio rerio and expressed heterologously in Escherichia coli . The recombinant E. coli exhibited the enantiopreference toward ( R )-styrene oxide with the maximum hydrolytic activity of 11.4 μmol min −1 (mg dcw) −1 . When the kinetic resolution was conducted with 40 mM of racemic styrene oxide, enantiopure ( S )-styrene oxide was obtained with an enantiomeric excess (ee) higher than 99 and 23.5% yield at 30 min. These results demonstrate that the recombinant fish EH has the possible application as a biocatalyst for the production of enantiopure epoxides.

The cruciferous vegetables such as Chinese cabbages and broccoli are known to have anticancer phytochemicals, and the consumption of cruciferous vegetables has been proposed to protect against various cancers. The anticarcinogenic properties of some Chinese cabbage extracts and sulforaphane glucosinolate (SFN) were assessed by examining their ability to prevent the inhibition of gap junctional intercellular communication (GJIC) induced by hydrogen peroxide (H2O2) in WB-F344 normal rat liver epithelial cells. The cells were preincubated with Chinese cabbage extracts and SFN for 24 h followed by cotreatment with cells and H2O2 (750 microM) for 1 h. Chinese cabbage extracts and SFN prevented the inhibition of GJIC and phosphorylation of gap junction protein connexin43 (Cx43) by H2O2 treatment. Chinese cabbage extracts and SFN were able to prevent the inhibition of GJIC through the blocking of Cx43 phosphorylaton and inactivation of ERK 1/2 and p38 MAP kinase. The results suggest that cruciferous vegetables and their components, SFN, may exert the anticancer effect by targeting the GJIC as a functional dietary chemopreventive agent.

A new type of biofilter, the rotating drum biotrickling filter (RDBF) system, was developed and operated to remove styrene from waste gas stream. Porous polyurethane foam sheets were used as a packing material for the RDBF and a pure culture of the Gram-positive bacterium Brevibacillus sp. SP1 was as an inoculum. The reactor showed a short start-up period of 18 days. Once uniform biofilms were developed on the packing, a high and stable removal of styrene over 95 % was observed at an incoming concentration of 200 ppmv and a retention time of 0.5 min. The maximum elimination capacity was estimated to be 125 g/m3/hr. The outstanding performance was attributed to an efficient gas-liquid mass transfer and proper supply of nutrient solution to the packing during the rotation of the drum. However, this performance of the RDBF was not maintained longer than 7 days because of the clogging of the open pores in the polyurethane foam due to an excessive growth of the biofilms. This result indicates that the RDBF has great potential as a gas purification system if a proper method to control the biofilm growth is developed.

Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells.

A tomographic deconvolution technique using the Fourier transformation has been applied for the reconstruction of asymmetric soot structure. Local soot volume fraction distribution can be identified from line-of-sight integrated data using light extinction measurements with multi-angular scanning. A peak-following interpolation technique was adopted to effectively increase the number of scanning angles. The results showed that the peak-following interpolation has improved the accuracy of reconstruction compared to the arithmetic interpolation in determining the local soot volume fraction. The measurement from a laser-induced incandescence technique substantiated the validity of the reconstruction technique.

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.

A mesh superposition technique is presented for an efficient finite element analysis. The formulation of the method is given for both single-field assumed displacement finite element models and two-field assumed strain finite element models. Refined local mesh is superimposed on global mesh for the region of interest. It is an adaptive mesh refinement method, which allows local refinement of the mesh without introducing transition region or multi-point constraints. By applying appropriate boundary conditions on the local superimposed mesh, singularity in the global stiffness matrix can be avoided and inter-element compatibility conditions can be satisfied. Effectiveness of the present technique is demonstrated by means of numerical examples of linear static, dynamic and buckling problems of elasticity. Moreover, effectiveness of the present procedure is tested for problems with curved geometries and with distorted grids. Also, various solutions schemes are investigated for effective analysis using the present method.

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.

Background Chronic rhinosinusitis with nasal polyps (CRSwNPs) or CRS without nasal polyps (CRSsNPs) is characterized by persistent inflammation of sinonasal mucosa. No one causative factor fully explains for the pathological manifestations of CRS. Endogenous hydrogen sulfide (H2S) has been shown to participate in inflammatory diseases, functioning as an inflammatory mediator in various organs. We analyzed the contents and synthesis activity of H2S, the expression and distribution pattern of H2S-generating enzymes, cystathione β-synthase (CBS), and cystathione γ-lyase (CSE) in CRSwNPs and CRSsNPs. The effects of H2S on the expression of CRS-relevant cytokines and the effects of cytokines on the expression of CBS and CSE were assessed in an in vitro experiment. Methods The contents and synthesis activity of H2S and the expression and distribution pattern of CBS and CSE in sinus mucosa were evaluated using spectrophotometry, real-time polymerase chain reaction, Western blot, and immunohistochemistry. Cultured epithelial cells were used to elucidate the effects of H2S donor, sodium hydrosulfide (NaHS), on the expression of CRS-relevant cytokines and the effects of cytokines on H2S-generating enzymes expression. Results The contents and synthesis activity of H2S were increased in CRSwNPs and CRSsNPs. CBS and CSE were localized to the superficial epithelium and submucosal glands, but CSE was also found in vascular endothelium. N S induced increased expression of IL-4, IL-5, interferon γ, and TNF-α. CBS and CSE expression in cultured cells was up-regulated by CRS-relevant cytokines. Conclusion H2S levels are increased in CRS, contributing to increased production of cytokines. These results suggest that H2S may function as inflammatory mediator in CRS.

Distributions of flame temperature in silica generating coflow diffusion flames have been measured using coherent anti-Stokes Raman spectroscopy (CARS) and qualitative measurements of OH radical concentrations have been made utilizing planar laser-induced fluorescence (PLIF). Silica particles have been visualized through the plane images of light scattering from particles. The results show that aerosol generation due to chemical reactions can significantly affect thermal and chemical characteristics of hydrogen–oxygen diffusion flames. When SiCl4 is added to a flame, the temperature in non-reacting zone decreases due to the increases in both specific heat and density of the gas mixture while the flame temperature increases in the particle formation zone due to exothermal chemical reactions of hydrolysis and oxidation of SiCl4. It has also been found that OH concentration decreases dramatically in the particle formation zone, which can be attributed to both the generation of HCl and the consumption of O2 and H2O during silica formation.

The evolution of non-spherical silica particles in a counterflow diffusion flame has been studied considering the effects of convection, diffusion, thermophoresis, chemical reactions, coagulation and coalescence. The counterflow geometry provides a one-dimensional flow field along the stagnation point streamline which greatly simplifies the analysis of non-spherical particle growth. Flame analysis of multi-step chemical reactions of hydrogen/oxygen including both oxidation and hydrolysis of SiCl 4 has been done to predict flame temperatures, concentrations of gas species and particle generation. The present prediction of flame temperatures was in good agreement with the previous experimental data. Two-dimensional aerosol dynamics in which both particle volume and surface area are independent variables has been then analyzed to obtain the evolution of non-spherical particles which has been compared with the previous experimental data. Several different models of coalescence of silica particles were studied; viscous flow sintering, atomistic diffusion sintering, fast sintering and hybrid sintering models. The use of hybrid sintering model yielded the best agreement with the previous experimental data. Since the collision cross section of non-spherical particles is larger than that of spherical particles having the same volume, coagulation of particles was obviously shown to be enhanced. The important role of axial particle diffusion has been identified in the counterflow diffusion flame. Bi-modal size distributions were obtained at some flame heights.

OBJECTIVE: The objective of our study was to analyze MR images of vascular leiomyoma of the extremity and to compare these images with histopathologic findings to determine if a correlation exists. CONCLUSION: T2-weighted MR images of vascular leiomyoma of an extremity showed a mass with mixed areas that were both hyper- and isointense to skeletal muscle and also revealed a hypointense rim; these images correlate with histopathologic findings of smooth muscle, vessels, fibrous tissue, an intravascular thrombus, and a fibrous capsule.

Sooting characteristics in laminar diffusion flames have been studied experimentally for ethylene–propane mixtures, and a synergistic effect from mixture fuels has been observed. Soot volume fraction and polycyclic aromatic hydrocarbon (PAH) concentration are increased when a small amount of propane is added to ethylene diffusion flames. Considering C2H2 concentrations and adiabatic flame temperatures, the experimental results indicate that H-abstraction–C2H2-addition (HACA) reaction alone is insufficient to explain soot inception and growth processes in diffusion flames of ethylene–propane mixtures. The synergistic effect of fuel mixture is discussed, emphasizing the importance of C3 recombination reaction during the initial ring formation process for incipient PAHs. The results of soot number density and particle size in low-temperature soot growth region also support continuous soot inception via PAH agglomeration. Therefore, it is suggested that PAHs are directly involved in the soot particle inception processes. The synergistic effect is less significant for ethylene–ethane mixtures compared to ethylene–propane mixtures.