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Microbial bioconversion of a given substrate is considered an efficient and eco-friendly tool for value-added industrial compound generation from natural products. Among natural products, unsaturated fatty acids have been used as substrates to produce various functional hydroxy fatty acids. In this study, we report the production of 7,10-dihydroxy-8(E)-hexadecenoic acid (DHD) from palmitoleic acid by a new strain, Pseudomonas aeruginosa KNU-2B. KNU-2B efficiently produced DHD from palmitoleic acid and required a strong alkaline condition for maximum DHD production. The maximum DHD amount produced under pH 10.0 and 48-h incubation at 27 °C and 150 rpm was 219.5 mg/100 mL culture. Other important nutritional factors were also investigated to obtain optimum DHD production.

BACKGROUND Plasma epidermal growth factor receptor (EGFR) mutation tests are less invasive than tissue EGFR mutation tests. We determined which of two kits is more efficient: cobas EGFR Mutation test v2 (cobasv2; Roche Molecular Systems, Pleasanton, CA, USA) or PANAMutyper-R-EGFR (Mutyper; Panagene, Daejeon, Korea). We also evaluated whether pleural effusion supernatant (PE-SUP) samples are assayable, similar to plasma samples, using these two kits. METHODS We analyzed 156 plasma and PE-SUP samples (31 paired samples) from 116 individuals. We compared the kits in terms of accuracy, assessed genotype concordance (weighted κ with 95% confidence intervals), and calculated Spearman's rho between semi-quantitatively measured EGFR-mutant levels (SQIs) measured by each kit. We also compared sensitivity using 47 EGFR-mutant harboring samples divided into more-dilute and less-dilute samples (dilution ratio: ≥ or

Conversion of free fatty acids into monoacylglycerol gives rise to new structural properties, particularly amphipathic property. Therefore, monoacylglycerols are widely used in pharmaceutical and food industries and are also reported to facilitate better absorption into the human body. A functional fatty acid when transformed into a monoacylglycerol will possibly conserve both the original functionality and amphipathic property. The compound 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was generated from oleic acid by Pseudomonas aeruginosa PR3 and was known to contain antimicrobial activities against a broad range of food-borne and plant pathogenic bacteria. Here, we attempted to convert DOD into its monoacylglycerol form using lipase for producing an amphipathic antibacterial agent. Consequently, the monoacylglycerol of DOD (DOD-MAG) was successfully produced by coincubating DOD, glycerol, and lipase at 30 °C. The maximum conversion yield reached 70% after 12 h of incubation. Antibacterial activity of DOD-MAG was enhanced by 8 times from the original activity of DOD against food-borne bacteria.

Cell-free synthesis has been adopted in the bioconversion process due to its known advantages, such as fast production rate, high product content, and no substrate/product inhibition effect. In this study, the cell-free supernatant of Pseudomonas aeruginosa was used to improve the production of 7,10‐dihydroxy‐8(E)‐octadecenoic acid (DOD) from oleic acid. DOD production using cell-free supernatant demonstrated reduction in bioconversion duration and higher product concentration than conventional method using whole cell culture. The maximum DOD concentration (6.41 g/L) was obtained after 36 h of biotransformation using 1 % v/v oleic acid as a substrate with a productivity of 0.178 g/L/h and a yield of 74.8 %. DOD concentration, productivity, and yield using cell-free supernatant were 2.12, 7.12, and 2.22 times higher, respectively, than using the conventional whole cell culture method. Of the carbon and nitrogen sources used in pre-culture, galactose and sodium glutamate along with diammonium phosphate were found to be the most effective for DOD production. An incubation temperature of 27 °C and pH 8.0 were found to be most favorable for DOD production. In addition, sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis demonstrated the presence of enzymes related to DOD production in the cell-free supernatant, which was substantiated by performing DOD production experiment using the supernatant enzymes extracted from protein gel bands with oleic acid as a substrate. To the best of our knowledge, this is the first report on DOD production using a cell-free supernatant and verifying the existence of the relevant enzymes in the cell-free supernatant. Compared to whole cell process, cell-free DOD production holds several advantages, including higher DOD productivity which could be beneficial for large-scale production.

Background: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. Methods: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George’s Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. Results: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37–88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16, p &lt, 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45, 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. Conclusions: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.

Synthetic oleochemical esters of polyols and fatty acids are biodegradable and possess desirable technical and ecological properties. Trimethylolpropane (TMP) triester has been widely applied as a hydraulic fluid. TMP triester was effectively synthesized by lipase-catalyzed esterification from TMP and high oleic fatty acid from palm oil using an immobilized lipase. The immobilized lipase was prepared with liquid Lipozyme TL 100 L from Thermomyces lanuginosus with Duolite A568 as a carrier. The effects of temperature, enzyme loading, vacuum level, and water activity of the enzyme on the synthesis of TMP triester were investigated. The optimum temperature, enzyme loading, and vacuum level were 60 °C, 15% (based on total substrate), and 6.7 kPa, respectively. The optimum water activity range of the enzyme was 0.5–0.9. Under the optimum conditions, the maximum conversion reached up to 95% after 9 h. No significant differences in physical properties were observed between TMP triester from this study and a commercial TMP triester prepared by chemical catalyst.

A 9,10-bis(morpholinopropylaminomethyl)anthracene ( 1 )-Fe 3+ chelate was designed, synthesized, and characterized by FT-IR, 1 H- 1 H COSY and 1 H- 1 H ROESY NMR studies. The in situ -generated Fe 3+ ensemble selectively detected putrescine ( Put ) and cadaverine ( Cad ) through a turn-off response via a decomplexation process in DMSO-H 2 O (1:1 v/v) at pH 7.3 (HEPES buffer). Furthermore, the in situ -generated ensemble can effectively differentiate biogenic aliphatic di- and triamines from a broad range of aliphatic monoamines (including basic amino acids) and aromatic amines (including polyamines). The lowest limit of detection (LOD) for Put and Cad were 33 ppb and 120 ppb, respectively, in mixed aqueous medium. The decomplexation aided turn-off response by the sequential addition of Put and Cad furnished good association constants [ K sv = 2.30 × 10 6 M −1 , and 9.95 × 10 5 M −1 in a HEPES-buffered DMSO-H 2 O (1:1, v/v) medium, respectively]. Furthermore, highly robust vapor phase detections of Put and Cad were also demonstrated using the fluorescent 1 ·Fe 3+ (1:2) ensemble coated on neutral alumina. Cheap ensemble-coated paper strips selectively detected Cad and Put among a variety of biogenic amines. By utilizing complexation/decomplexation processes aided through sequential addition of Fe 3+ and Put / Cad an INHIBIT photonic logic gate and its fluorogenic tracking was demonstrated in primitive- eukaryotic cell lines.

Despite negative public opinion, the role of the Korean government has expanded, while overcoming two rounds of global financial crises. The phenomenon of the re-swelling state is mainly attributed to the strengthening of the central bureaucracy, in particular the financial bureaucracy, rather than the whole central government or the state. The argument of the strengthening of the ‘state’ or the ‘government’ after economic crises might be subject to the error of generalization. Through the two rounds of economic crises, the financial bureaucracy succeeded in acquiring the authority of market supervision and industrial support. In consequence, the bureaucracy's institutional supremacy within the government grew less challenged. The central bureaucracy was no longer the loyal servant to the President. It has reinforced its institutional strength and autonomy vis-a-vis the President, the National Assembly, the Central Bank and civil society, under the pretext of building up the rational and autonomou...

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections with multi-drug resistance needs effective and alternative control strategies. In this study we investigated the adjuvant effect of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against multidrug-resistant S. aureus (MDRSA) strain 01ST001 by disc diffusion, checker board and time kill assays. Further the membrane targeting action of 7,10-EODA was investigated by spectroscopic and confocal microscopic studies. 7,10-EODA exerted synergistic activity along with β-lactam antibiotics against all clinical MRSA strains, with a mean fractional inhibitory concentration index below 0.5. In time-kill kinetic study, combination of 7,10-EODA with oxacillin, ampicillin, and penicillin resulted in 3.8–4.2 log10 reduction in the viable counts of MDRSA 01ST001. Further, 7,10-EODA dose dependently altered the membrane integrity (p

The simultaneous synthesis of a phytosteryl ester and enrichment of stearidonic acid (SDA) were performed via a one-step lipase-catalyzed esterification of fatty acids from Ahiflower™ seed oil with phytosterol. A commercial lipase (Lipase OF) from Candida rugosa was employed as a biocatalyst. Three solvents were screened and cyclohexane was selected as a suitable reaction medium. The effects of enzyme loading, temperature, and solvent amount were investigated. The conversion as well as the SDA content were significantly improved by adding molecular sieves after 1 h of reaction. The optimum conditions were the enzyme loading of 10% (based on the total substrate weight), the temperature of 30 °C, and the solvent amount of 4 mL (based on a substrate weight of 2 g), respectively. The maximum conversion and SDA content in the residual fatty acid were 81 mol% and 58 mol%, respectively, under the optimum conditions. The SDA content increased a 3.4-fold from 17 mol% in Ahiflower™ seed oil to 58 mol%.

Lipase is one of the widely used biocatalysts, which is well studied for its application in industrial production. Recently, lipases with special characteristics such as thermo-stability, alkaline-, acidic nature, and cold-activity, have gained attention for effective applications in specific purposes. Previously, Pichia lynferdii NRRL Y-7723 was reported to produce high amounts of extracellular cold-active lipase (Kim et al., 2010). In this study, we report the identification of lip1 gene that encodes an extracellular cold-active lipase from P. lynferdii NRRL Y-7723. The open reading frame of the gene consisted of 1122 bp of nucleotides that encoded a protein with 373 amino acids. The deduced molecular weight and isoelectric point were 41.8 kDa and pH 5.82, respectively. The lip1 gene was cloned into a bacterial expression vector, and the recombinant lipase was successfully expressed and purified. Several parameters of the recombinant lipase were analyzed, and Lip1 showed high activity at low temperature.

Lipase-mediated transesterification of soybean oil with a blending alcohol consisting of methanol and 1-butanol for synthesis of fatty acid esters was carried out. Lipase from Thermomyces lanuginosa (Lipozyme TL IM) was used as a biocatalyst. The lipase was purchased from Novozymes (Seoul, Republic of Korea). The effects of the molar proportions of methanol and 1-butanol in the blending alcohol, reaction temperature, enzyme loading and water content were investigated, for reaction optimization. The relative consuming rates of methanol and 1-butanol during the reaction were also explored. Among seven different ratios of alcohol blends employed in this study, that containing 80 mol% methanol gave the highest yield of fatty acid esters. Optimum reaction temperature, enzyme loading, and water content were 30 °C, 15% (based on the substrate weight), and 0.3% (based on the substrate weight), respectively. Water influenced significantly the reaction rate and yield. On the transesterification, the degree of reaction of methanol was higher than that of 1-butanol and the presence of 1-butanol contributed to increase of the reaction rate as well as yield. The maximum yield of ca. 98 wt% was achieved under the optimized condition.

ObjectiveHeterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), serine/arginine-rich splicing factor 1 (SRSF1), and SRSF3 are splicing regulators associated with oncogenesis. However, the alterations of SF proteins and their diagnostic values in cervical cancer are unclear. To apply SFs clinically, effective marker selection and characterization of the target organ properties are essential.Materials and MethodsWe concurrently analyzed HNRNPA1, SRSF1, SRSF3, and the conventional tumor markers squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in cervical tissue samples (n = 127) using semiquantitative immunoblotting. In addition, we compared them with p16 (cyclin-dependent kinase inhibitor 2A [CDKN2A]), which has shown high diagnostic efficacy in immunohistochemical staining studies and has been proposed as a candidate protein for point-of-care screening biochemical tests of cervical neoplasia.ResultsHNRNPA1, higher molecular weight forms of SRSF1 (SRSF1-HMws), SRSF3, CEA, and p16 levels were higher (P < 0.05) in cervical carcinoma tissue samples than in nontumoral cervical tissue samples. However, the levels of SRSF1-Total (sum of SRSF1-HMws and a lower molecular weight form of SRSF1) and SCCA, a commonly used cervical tumor marker, were not different between carcinoma and nontumoral tissue samples. In paired sample comparisons, HNRNPA1 (94%) showed the highest incidence of up-regulation (carcinoma/nontumor, >1.5) in cervical carcinoma, followed by p16 (84%), SRSF1-HMws (69%), SRSF3 (66%), CEA (66 %), SCCA (32%), and SRSF1-Total (31%). HNRNPA1 (92%) and p16 (91%) presented the two highest diagnostic accuracies for cervical carcinoma, which were superior to those of SRSF3 (75%), SRSF1-HMws (72%), CEA (72%), SCCA (59%), and SRSF1-Total (55%).ConclusionsOur results identified that HNRNPA1 is the best diagnostic marker among the SFs and conventional markers given its excellent diagnostic efficacy for cervical carcinoma, and it has a p16-comparable diagnostic value. We suggest that HNRNPA1 is an additional effective target protein for developing cervical cancer detection tools.

Microbial production of hydroxy fatty acids (HFAs) was widely studied because of important biological properties of HFAs. Among microorganisms producing HFAs, Pseudomonas aeruginosa PR3 was well known to produce various HFAs from different unsaturated fatty acids. Recently, a new variant species of P. aeruginosa PR3 was isolated and characterized, showing improved efficiency for producing 7,10-dihydroxy-8(E)-octadecenoic acid from oleic acid. In this study, we report the production of 7,10,12-trihydroxy-8(E)-octadecenoic acid (TOD) from ricinoleic acid by the newly isolated P. aeruginosa KNU-2B. TOD was efficiently produced from ricinoleic acid by KNU-2B with the maximum conversion yield of 56.7% under the optimum reaction conditions of pH 8.0 and 48-h incubation at 27 °C, 150 rpm. Under optimized reaction conditions, maximum TOD production reached 340.3 mg/100 mL of the culture. However, requirement of nutritional factors by KNU-2B for production of TOD were considerably different from those by PR3 strain.

Histone deacetylase (HDAC) inhibition offers the potential for anti-cancer effects in a variety of cancers, since HDAC plays an important role in cancer development and progression. Thus, we demonstrated the therapeutic efficacy of the new HDAC inhibitor, CG200745, in comparison with existing HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA) in non-small lung cancer cells. Compared with SAHA, CG200745 had inhibited cell viability and HDACs expression, and induced apoptosis, ROS and mitochondrial dysfunction. CG200745 also significantly reduced tumor volume in vivo compared with SAHA. We observed increased apoptosis and ROS after treatment with survivin siRNA and CG200745, whereas overexpression of survivin protected against apoptosis and ROS by CG200745. We next demonstrated that CG200745 reduced the acetylation of survivin and that survivin is present in the nucleus. CG200745 showed a decrease in the stability of survivin. Furthermore, CG200745 increased expression of actylated-p53 and decreased activity of survivin promoter. We found that -189 ~ -11 plays an important role in the p53 binding site of the survivin promoter, and binding of p53, is increased depending on the CG200745 concentration. Collectively, these data shows that CG200745 induces apoptosis more than SAHA through down-regulation of survivin in NSCLC cells. CG200745 reduces the stability of survivin by inhibiting deacetylation of survivin, and decreases the promoter activity of survivin by acetylating p53.

Background: Oleanolic acid acetate (OAA) is a triterpenoid compound derived from Vigna angularis and is known to have various effects such as tumor suppression, kidney protection, and anti-inflammatory effect. However, research on the inhibition mechanisms of OAA in fibrosis is limited. In this study, we investigated the effects of OAA on bleomycin-induced pulmonary fibrosis in mice and its underlying mechanism in vivo and in vitro. Methods: The in vivo effect of OAA was evaluated by measuring histological changes, mRNA, BALF, collagen content and protein expression in bleomycin-indcued pulmonary fibrosis mice. The in vitro effect of OAA was evaluated proliferation, mRNA and protein expression of A549 and NIH3T3 cells were analyzed by CCK-8, real-time PCR and Western blot respectively. Mice were treated with bleomycin and OAA was orally administered for 14 days after bleomycin injection, and A549 and NIH3T3 cells were induced by TGF-b1 for 48 hours. Results: OAA treatment reduced inflammatory cell count, cytokine level and soluble protein accumulation in bronchoalveolar lavage fluid, and ameliorated weight loss and lung weight, lung histopathological abnormality and pulmonary collagen deposition. OAA also inhibited the expression of EMT and fibrotic markers in vivo and in vitro. Moreover, levels of TGF-β1, p-Smad2, and p-Smad3 in vivo and in vitro decreased after OAA treatment. Conclusion: OAA inhibits bleomycin-induced pulmonary fibrosis by inhibiting EMT and may be a novel therapeutic drug for the treatment of idiopathic pulmonary fibrosis.

Conversion of free fatty acids into monoacylglycerol gives rise to new structural properties, particularly amphipathic property. Therefore, monoacylglycerols are widely used in pharmaceutical and food industries and are also reported to facilitate better absorption into the human body. A functional fatty acid when transformed into a monoacylglycerol will possibly conserve both the original functionality and amphipathic property. The compound 7,10-dihydroxy-8(

Malignancy and tuberculosis are common causes of lymphocytic exudative pleural effusion. However, it is occasionally difficult to differentiate malignant pleural effusion from tuberculous pleural effusion. Vascular endothelial growth factor (VEGF) is a critical cytokine in the pathogenesis of malignant pleural effusion. Endocan is a dermatan sulfate proteoglycan that is secreted by endothelial cells. Importantly, endocan mediates the vascular growth-promoting action of VEGF. The aim of this study was to evaluate the diagnostic significance of VEGF and endocan in pleural effusion. We thus measured the levels of VEGF and endocan in the pleural effusion and serum samples of patients with lung cancer (n = 59) and those with tuberculosis (n = 32) by enzyme-linked immunosorbent assay. Lung cancer included 40 cases of adenocarcinoma, 13 of squamous cell carcinoma, and 6 of small cell carcinoma. Pleural effusion VEGF levels were significantly higher in the malignant group than in the tuberculosis group (2,091.47 ± 1,624.80 pg/mL vs. 1,291.05 ± 1,100.53 pg/mL, P < 0.05), whereas pleural effusion endocan levels were similar between the two groups (1.22 ± 0.74 ng/mL vs. 0.87 ± 0.53 ng/mL). The areas under the curve of VEGF and endocan were 0.73 and 0.52, respectively. Notably, the VEGF levels were similar in malignant pleural effusion, irrespective of the histological type of lung cancer. Moreover, no significant difference was found in the serum VEGF and endocan levels between patients with lung cancer and those with tuberculosis. In conclusion, high VEGF levels in pleural effusion are suggestive of malignant pleural effusion.

We analyzed the antimicrobial potential of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against methicillin-resistant and -sensitive S. aureus (MRSA and MSSA). The anti-staphylococcal activity of 7,10-EODA and its consequences on cell physiology was determined by disc diffusion, broth microdilution, and flow cytometry. Anti-virulence activity of 7,10-EODA was evaluated by bioassays. 7,10-EODA was anti-staphylococcal with minimum inhibitory concentration (MIC) range of 125-250 mg/L. 7,10-EODA exhibited a dose response and inhibited MRSA 01ST001 by 90.5% and ATCC 29213 (MSSA) by 85.3% at 125 mg/L. MIC of 7,10-EODA permeabilized >95 % of MRSA 01ST001 cells to small molecules. Sublethal dose of 7,10-EODA was non-toxic but markedly reduced the hemolytic, coagulase, and autolytic activities of MRSA and MSSA at 15.6 mg/L. The results provide a lead for the utilization of natural furan fatty acids as novel anti-MRSA agents.

The use of computed tomography (CT) in the diagnosis of urinary tract infection (UTI) has rapidly increased recently at acute stage, but the CT findings associated with bacteremia in UTI patients are unknown. 189 UTI patients were enrolled who underwent a CT scan within 24 h after hospital admission. We classified CT findings into eight types: a focal or multifocal wedge-shaped area of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and renal and perirenal abscess. A retrospective analysis was conducted to evaluate the CT findings associated with bacteremia. The mean age of these patients was 60 ± 17.2 years, and 93.1 % were women. Concurrent bacteremia was noted in 40.2 % of the patients. Abnormal CT findings were noted in 96.3 % of the patients and 62.4 % had two or more abnormal findings. The most frequent abnormal CT finding was a focal or multifocal wedge-shaped area of hypoperfusion (77.2 %), followed by perinephric fat stranding (29.1 %). Perinephric fat stranding, hydronephrosis, and the presence of two or more abnormal CT findings were significantly associated with bacteremia in patients with community-acquired UTI. In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.009-1.062], two or more abnormal CT findings (OR 3.163; 95 % CI 1.334-7.498), and hydronephrosis (OR 13.160; 95 % CI 1.048-165.282) were significantly associated with bacteremia. Physicians should be aware that appropriate early management is necessary to prevent fatality in patients with these CT findings.

// Byong-Ki Cha 1, * , Young-Suk Kim 2, * , Ki-Eun Hwang 2 , Kyung-Hwa Cho 2 , Seon-Hee Oh 3 , Byoung-Ryun Kim 4 , Hong-Young Jun 5 , Kwon-Ha Yoon 6 , Eun-Taik Jeong 2 , Hak-Ryul Kim 2 1 Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical School, Jeonbuk, Korea 2 Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea 3 Department of Premedicine, School of Medicine, Chosun University, Gwangju, Korea 4 Department of Obstetrics & Gynecology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea 5 Imaging Science Research Center, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea 6 Departments of Radiology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea * These authors have contributed equally to this work Correspondence to: Hak-Ryul Kim, email: kshryj@wku.ac.kr Keywords: celecoxib, sulindac, EMT, SIRT1, lung cancer Received: December 16, 2015 Accepted: July 26, 2016 Published: August 09, 2016 ABSTRACT The non-steroidal anti-inflammatory drugs (NSAIDs) celecoxib and sulindac have been reported to suppress lung cancer migration and invasion. The class III deacetylase sirtuin 1 (SIRT1) possesses both pro- and anticarcinogenic properties. However, its role in inhibition of lung cancer cell epithelial-mesenchymal transition (EMT) by NSAIDs is not clearly known. We attempted to investigate the potential use of NSAIDs as inhibitors of TGF-β1-induced EMT in A549 cells, and the underlying mechanisms of suppression of lung cancer migration and invasion by celecoxib and sulindac. We demonstrated that celecoxib and sulindac were effective in preventing TGF-β1-induced EMT, as indicated by upregulation of the epithelial marker, E-cadherin, and downregulation of mesenchymal markers and transcription factors. Moreover, celecoxib and sulindac could inhibit TGF-β1-enhanced migration and invasion of A549 cells. SIRT1 downregulation enhanced the reversal of TGF-β1-induced EMT by celecoxib or sulindac. In contrast, SIRT1 upregulation promoted TGF-β1-induced EMT. Taken together, these results indicate that celecoxib and sulindac can inhibit TGF-β1-induced EMT and suppress lung cancer cell migration and invasion via downregulation of SIRT1. Our findings implicate overexpressed SIRT1 as a potential therapeutic target to reverse TGF-β1-induced EMT and to prevent lung cancer cell migration and invasion.

BACKGROUND/AIMS Brain and bone metastases are common in patients with lung cancer. The development of metastasis is associated with poor survival in lung cancer patients. Although tumor morphologic features on radiographs are routinely assessed for differentiation between benign and malignant lung nodules, they are not used to predict metastasis. We assessed morphologic features of pulmonary adenocarcinomas with brain/bone metastasis on computed tomography (CT) to identify related factors for metastasis. METHODS We performed a retrospective analysis of initial chest CT findings (size, type of contour, percentage of necrosis, enhancement, presence or absence of calcification, and air cavity) from 2009 to 2010 of patients with brain or bone metastasis and compared the findings with those of patients without metastases. RESULTS In total, 128 patients were included (78 men, 52 women; mean age 69 years; range, 36 to 87). Nineteen patients had brain metastases and 32 had bone metastases. Morphologic features associated with brain metastasis included size ≥ 50 mm (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.24 to 9.17; p = 0.013), necrosis ≥ 30% (OR, 4.51; 95% CI, 1.62 to 12.55; p =0.002), and presence of calcification (OR, 3.97; 95% CI, 1.16 to 13.55; p = 0.035). Morphologic features associated with bone metastasis included necrosis ≥ 30% (OR, 4.639; 95% CI, 1.98 to 10.82; p < 0.001) and T 3 to 4 stage (OR, 2.53; 95% CI, 1.07 to 6.00; p = 0.031). CONCLUSIONS We found that necrosis ≥ 30% was associated with pulmonary adenocarcinoma with brain and bone metastasis at initial chest CT morphologic feature. To validate these results, further research should be conducted.

We report first case of pulmonary siderosis appearing as a consolidation upon radiological examination and being misdiagnosed as pneumonia. A 59-year-old man visited our hospital with a cough and sputum that had persisted for more than a month. He had undergone chest computed tomography (CT) after abnormal findings on chest X-ray at other hospitals. Based on the chest CT results, he was diagnosed with pneumonia. He was then administered antibiotics for 3 weeks, but there was no improvement. We identified the patient's occupational history first, and then performed bronchoalveolar lavage and chest CT-guided transthoracic lung biopsy. The obtained specimen showed alveolar, macrophage-containing, Prussian blue-positive iron particles. Based on the results, we diagnose/d the patient with pulmonary siderosis. We advised him to discontinue his job. He is currently undergoing observation, and has not shown any special symptoms. Keywords: Pulmonary siderosis, Bronchoalveolar lavage, Transthoracic lung biopsy

International audience; Degradation of palmitoleic acid (C 16:1x7), the main fatty acid component of sea ice-associated (sympagic) diatoms, was monitored in Arctic sea ice at the beginning of ice melting and in the underlying sinking particles and superficial bottom sediments. In sea ice, degradation of sympagic algae involved biotic oxidation induced by 10S-DOX-like lipoxygenase of unknown salinity-stressed attached bacteria, while photo-and autoxidation were limited. In the water column, strong hydratase and Z/E isomerase activity were observed. Hydration of unsaturated fatty acids seems to be a detoxification strategy, which is essential for bacterial survival when associated with free fatty acid-rich environments such as ice algae. In contrast, Z/E isomerisation of palmitoleic acid was attributed to the release of Fe 2+ ions during radical-induced damage of the active site of the bacterial 10S-DOX-like lipoxygenase and Z/E isomerases. Due to the poor physiological state of their attached bacteria resulting from salinity stress in brine channels or toxicity of free ice algae fatty acids, sympagic algae appeared to be only very weakly biotically degraded within the water column. In bottom sediments, free radicals resulting from 10S-DOX-like lipoxygenase activity induced a strong autoxidation of the ice algal material. The presence in bottom sediments of a significant proportion of oxidation products resulting from 10S-DOX-like lipoxygenase activity attested to the strong contribution of sea ice-derived OM released during the early stages of ice melt prior to depo-sition in the sediments. However, on the basis of the highest fatty acid photooxidation state observed in these sediments, an additional contribution of highly photooxidized material (ice algal material released at the end of ice melting or open water phytoplankton) seems likely. The degradation of hydroperoxides, resulting from biotic and abiotic degradation of palmitoleic acid, appeared to involve: (i) homolytic cleav-age of the peroxyl group affording the corresponding hydroxy-and oxoacids, (ii) reduction to the corresponding hydroxyacids by peroxygenases, (iii) heterolytic proton-catalysed cleavage and (iv) conversion to allylic 1,4-diols by diol synthases and hydroperoxide isomerases.

The tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein that has been related to drug resistance in some tumors. Epithelial-mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. The aim of the present study was to determine the role of TRAP1 on EMT in lung cancer cell lines and to evaluate the prognostic role of TRAP1 in NSCLC patients. We developed an in vitro model of acquired resistance to gefitinib by continuously treating HCC827 with escalating doses. The effects of TRAP1 on EMT and lung cancer migration and invasion in gefitinib resistance (GR) cells were examined by western blotting and confocal microscopy. Downregulation of TRAP1 through siRNA or G-TPP inhibited GR-induced EMT, as indicated by upregulation of E-cadherin, and downregulation of mesenchymal markers and transcriptional factors. TRAP1 expression was analysed by immunohistochemistry in a series of 97 NSCLC patients. TRAP1 expression correlates with poor outcome in NSCLC patients. We next showed that TRAP1 downregulation enhanced the reversal of TGF-β1-induced EMT and hypoxia-induced EMT. Furthermore, TRAP1 downregulation attenuated migration and invasion of HCC827GR cells. In conclusions, these results suggested that TRAP1 downregulation could overcome gefitinib resistance in NSCLC via EMT reversal in tumor microenvironment.

TNF receptor-associated protein 1 (TRAP1) has been reported to be upregulated in some tumors, and protected against apoptosis and oxidative stress. This study was designed to investigate overcoming gefitinib resistance in NSCLC through a mechanism-based approach using gamitrinib variant containing triphenylphosphonium (G-TPP), TRAP1 inhibitor. We developed an in vitro model of acquired resistance to gefitinib. The effects of G-TPP on apoptosis and ROS-dependent mitochondrial dysfunction in HCC827GR cells were examined by annexin V binding assay, MitoSoX, and immunoblot analysis. and we tested the effects of pretreated with NAC or DPI, free radical scavenger. In addition, TRAP1 and antioxidant MnSOD were respectively knocked down or overexpressed to determine its role in modulating ROS-mediated apotosis signals by G-TPP. Downregulation of TRAP1 through siRNA or G-TPP enhanced ROS-mediated apoptosis whereas TRAP1 overexpression attenuated ROS-mediated apoptosis induced by gefitinib. On the other hand, pretreatment with NAC or DPI prevents apoptosis induced by gefitinib and G-TPP. We next showed that the combination of gefitinib and G-TPP resulted in decreased expression of MnSOD in HCC827GR cells, not HCC827 cells. MnSOD siRNA and combined with gefitinib and G-TPP resulted in a greater apoptosis. In contrast, overexpression of MnSOD could confer protection against the apoptosis reduced by gefitinib and G-TPP. TRAP1 downregulation could overcome gefitinib resistance in NSCLC via ROS-mediated apoptotic pathway. Moreover, enhanced apoptosis by gefitinib and G-TPP in HCC827GR cells was due, at least in part, to the down-regulation of MnSOD.

Background Plasma epidermal growth factor receptor (EGFR) mutation tests are less invasive than tissue EGFR mutation tests. We determined which of two kits is more efficient: cobas EGFR Mutation test v2 (cobasv2; Roche Molecular Systems, Pleasanton, CA, USA) or PANAMutyper-R-EGFR (Mutyper; Panagene, Daejeon, Korea). We also evaluated whether pleural effusion supernatant (PE-SUP) samples are assayable, similar to plasma samples, using these two kits. Methods We analyzed 156 plasma and PE-SUP samples (31 paired samples) from 116 individuals. We compared the kits in terms of accuracy, assessed genotype concordance (weighted κ with 95% confidence intervals), and calculated Spearman's rho between semi-quantitatively measured EGFR-mutant levels (SQIs) measured by each kit. We also compared sensitivity using 47 EGFR-mutant harboring samples divided into more-dilute and less-dilute samples (dilution ratio: ≥ or

New polyurethanes were synthesized based on dihydroxy fatty acid obtained by the microbial conversion of olive oil. Monounsaturated 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was produced from olive oil by Pseudomonas aeruginosa PR3 and reacted with hexamethylene diisocyanate (HMDI) at different ratios to form polyurethanes. Fourier transform infrared spectroscopy and gas chromatography/mass spectrometry confirmed the synthesis of DOD. The thermal and tensile properties of the polyurethanes were investigated by differential scanning calorimetry, thermogravimetric analysis, and a universal testing machine. At an isocyanate/hydroxyl ratio of 1.4, the polyurethane exhibited an elongation at break of 59.2% and a high tensile strength of 37.9 MPa. DOD was also mixed with polycaprolactone diol or polyethylene glycol at different weight ratios and then reacted with HMDI to produce new polyurethanes of various properties. These polyurethanes displayed higher elongation at break and good thermal stability. This is the first report on the synthesis of polyurethanes based on DOD produced by the microbial conversion of vegetable oil.

Fatty acid methyl esters were synthesized from palm fatty acid distillate (PFAD) and methanol in a packed bed reactor via lipase-catalyzed esterification. The PFAD consisted of 91 wt% of free fatty acids, 2 wt% monoacylglycerides, 3 wt% diacylglycerides, and 4 wt% triacylglycerides. t-Butanol was employed as a reaction medium and a mixed enzyme consisting of Lipozyme TL IM from Thermomyces lanuginosus and Novozym 435 from Candida antarctica was employed as the biocatalyst. The effect of mixed enzyme was investigated and the optimum blending ratio (w/w) of Novozym 435 to Lipozyme TL IM was 5:95. Using the mixed enzyme, the optimum molar ratio (PFAD to methanol) and temperature were determined to be 1:6 and 30°C, respectively. Under the optimized conditions, the maximum yield of ca. 96% was achieved.

We report an unusual case of obstructive pneumonia due to an unknown eosinophilic mucoid impaction of the bronchi (MIB). A 54-year-old woman visited our hospital for investigation of abnormal shadows visible on a chest radiograph. Chest computed tomography and bronchoscopic examination revealed pneumonia due to MIB. Histopathological examination of biopsied mucosal tissue revealed extensive eosinophilic infiltration. With the exclusion of medical diseases that can cause eosinophilia, pneumonia due to eosinophilic mucoid impaction of the bronchi was diagnosed. The cause of the eosinophilia remained unknown. The pneumonia and mucoid impaction resolved after oral steroid therapy. (Korean J Med 2015;89:699-703)

Sugar derivatives are critically important in nutritional, pharmaceutical, and some non-food industries. Amino sugars are more important as essential components of many drugs, antibiotics, and biopolymers. Hence, a novel amino sugar compound is worthy of investigation for identification and production. A novel amino sugar compound was identified from crude extracts of Korean pine seed embryos. This new compound was isolated from extracts using traditional purification steps. The pure compound was white in color with a melting point of 145°C. HPLC, TLC, FT-IR, and NMR analyses of the compound indicated a trisaccharide form of amino mannose that was polymerized with β-(1→2) glycosidic bonding. Computer-aided NMR spectral analysis of the trisaccharide of 2-dehydro-2-mannosamine exhibited a 96% match with the 13C-NMR spectrum of the new compound.

Pemetrexed is a multitargeted antifolate used for the treatment of malignant mesothelioma and non-small cell lung cancer (NSCLC). However, the mechanism by which pemetrexed induces apoptosis remains unclear. In the present study, we investigated the involvement of reactive oxygen species (ROS) and sirtuin 1 (SIRT1) in pemetrexed-induced apoptosis in MSTO-211 malignant mesothelioma cells and A549 NSCLC cells. Pemetrexed enhanced caspase-dependent apoptosis, induced intracellular ROS generation, and downregulated SIRT1 in the MSTO-211 and A549 cells. Pemetrexed-induced apoptosis, which was prevented by pretreatment with N-acetyl-cysteine (NAC), was mediated by effects on the mitochondria, including mitochondrial membrane potential transition (MPT) and cytosolic release of cytochrome c, and also involved regulation of SIRT1 expression. Interference with SIRT1 expression using siRNA enhanced pemetrexed-induced apoptosis through mitochondrial dysfunction and ROS generation, whereas resveratrol, an activator of SIRT1, protected against pemetrexed-induced apoptosis. These results show that pemetrexed induces apoptosis in MSTO-211 mesothelioma cells and A549 NSCLC cells through mitochondrial dysfunction mediated by ROS accumulation and SIRT1 downregulation.