Prediction of organic pollutant removal using Corynebacterium glutamicum fermentation waste.

The disposal of bio-waste (e.g., Corynebacterium glutamicum) produced by the fermentation industry is a serious problem and has a negative impact on economic returns. Some fermentation waste can be recycled as livestock feed, but much cannot be used. Therefore, other recycling methods must be developed to increase its applications, for example, as an environmentally friendly adsorbent for the removal or recovery of chemicals. To broaden its application as an adsorbent, we carried out comprehensive experimental and theoretical analysis. From the experiments, adsorption affinity values between C. glutamicum and micropollutants were measured, and, based on the experimental values, we developed a predictive model. The experimental results reveal that the degree of adsorption is dependent on the structural properties of the micropollutants. In particular, the adsorbent has remarkable adsorption ability toward cations, whereas anionic and neutral compounds interact weakly with the adsorbent. In addition, we found that adsorption is affected by the sodium chloride concentration. Briefly, an increase in salt concentration increases the adsorption of anions, whereas the opposite behavior is observed for cations. In contrast, the adsorption of neutral compounds was not affected by the presence of salt. The modeling studies revealed that a linear free energy relationship model can be used to predict the adsorption affinity. Based on the developed model, we found that hydrogen-bond basicity, anionic coulombic interactions, and molecular volume are the main contributing factors to the adsorption model. However, to achieve the best predictability (a coefficient of determination (R2) of 0.902), additional parameters, such as the dipolarity/polarizability and dispersive interaction, should be included. This indicates that adsorption is a product of complex interactions.

Two-year treatment outcome of chronic hepatitis B infection treated with besifovir vs. entecavir: results from a multicentre study.

BACKGROUND & AIMS: We aimed to compare the viral suppression, safety and rate of drug resistance between besifovir (a new acyclic nucleotide analogue) and entecavir. METHODS: Treatment-naïve chronic hepatitis B patients receiving besifovir 90 mg (n=31), 150 mg (n=28) and entecavir 0.5 mg (n=30) were monitored for liver biochemistry, viral serology, HBV DNA levels, development of drug resistance mutations, and adverse events throughout 96 weeks of treatment. RESULTS: The mean decline of HBV DNA levels from baseline to week 96 were 5.29, 5.15, and 5.67 logs IU/ml for patients receiving besifovir 90 mg, 150 mg and entecavir 0.5 mg, respectively (p>0.05). Undetectable HBV DNA (<20 IU/ml) were achieved in 80.7%, 78.6%, and 80%; ALT normalization in 90.3%, 78.6%, and 93.3%; and loss of HBeAg in 20%, 21.4%, and 22.2% of patients respectively (all p>0.05). One patient receiving besifovir 90 mg had a virological breakthrough due to drug non-compliance. No patient developed drug resistance mutations. Ten patients had serious adverse events, which were not related to the study medications. The most common side effect related to besifovir was carnitine depletion. Carnitine supplements were prescribed to 83.9% and 100% of patients, who had low carnitine level for any one time during follow-up, receiving besifovir 90 mg and 150 mg respectively. No patient had increased creatinine>0.5 mg/dl from baseline. CONCLUSIONS: Besifovir had the same antiviral property as compared to entecavir over 96 weeks of treatment for chronic hepatitis B patients. Besifovir was well tolerated and also had a good clinical safety profile.

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B.

BACKGROUND: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients in preliminary studies. DESIGN: We aimed to compare the safety and antiviral activity of two doses of besifovir (90 mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry, including serum L-carnitine levels, were monitored. RESULTS: At week 48, in the intention-to-treat population, the proportion of patients achieving undetectable HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were -5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were -4.65, -4.55 and -4.67, respectively (p>0.05). There were no differences in the proportions of patients achieving normalisation of alanine aminotransferase (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%, respectively) among all three groups. None of the patients had resistant mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%) patients on besifovir had lowering of serum L-carnitine (not tested in entecavir patients). L-carnitine levels returned to normal with carnitine supplement. CONCLUSIONS: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation.

Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

OBJECTIVES: For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. MATERIALS AND METHODS: This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study. RESULTS: Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component. CONCLUSION: The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

Mental Health of Parents and Their Children: A Longitudinal Study of the Effects of Parents' Negative Affect on Adolescents' Pathological Gaming.

Parents' negative affect could lead to the deterioration of the mental state of their adolescent children. According to previous studies, children of parents who have symptoms of depression or anxiety are more likely to have mental problems. As one of the most important issues concerning adolescents with the rapid rise of screen time, the concern for pathological gaming among adolescents continues to intensify. Many studies have demonstrated the remarkable relationships between adolescents' pathological gaming and mental factors, but seldom examined them via longitudinal analysis. With three-year data from adolescents (N = 778) and their parents (N = 685) in South Korea, this study assessed the effects of parents' negative affect (depression and anxiety) on pathological gaming using adolescents' mental factors (i.e., aggression, ADHD, self-control). The results showed the critical role of parents' negative affect on their children's mental health, which finally leads to pathological gaming among adolescents. Depressive parents increased the degree of adolescents' aggression and ADHD, and decreased the degree of adolescents' self-control. Anxious parents increased the degree of adolescents' ADHD. Moreover, both adolescents' aggression and self-control mediated the relationship between parents' depression and adolescents' pathological gaming. Specifically, self-control was one of the most influential factors contributing to pathological gaming among adolescents.

Exploring the Mechanism of Pathological Gaming in Adolescents: Focused on the Mediation Paths and Latent Group Comparison.

Pathological gaming among adolescents has been reported to hamper the achievement of a balanced life and to threaten the development of social competencies. Despite the increasing social concerns on the adolescent users, however, the mechanism of gaming behavior of adolescents has not been sufficiently examined. This study explored the mechanism of pathological gaming among adolescents from 3-year longitudinal data of 778 Korean adolescent gamers, by analyzing the effects of negative affects (i.e., anxiety, loneliness, and academic stress) on the degree of pathological gaming through the mediation variables (i.e., aggression and self-control) based on the stimulus-organism-response (S-O-R) framework. Latent class analysis (LCA) was used to uncover potential risk groups, and through partial least squares-structural equation modeling (PLS-SEM) analysis, the mediation pathways to pathological gaming were compared between the risk group and the non-risk group. The results highlighted the key role of academic stress on the degree of pathological gaming. In the entire group, academic stress primarily increased pathological gaming through self-control. The mediation path of self-control was the most influential result in the risk group. Aggression was the key mediator between loneliness and pathological gaming in the non-risk group. The theoretical and practical implications of the results were discussed.

Pharmacokinetics, pharmacodynamics, and tolerability of the dipeptidyl peptidase IV inhibitor LC15-0444 in healthy Korean men: a dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study.

BACKGROUND: LC15-0444 is a selective inhibitor of dipeptidyl peptidase (DPP) IV under investigation in Korea for the treatment of type 2 diabetes. OBJECTIVE: The aim of this study was to investigate the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of a single dose of LC15-0444 in healthy male subjects. METHODS: A dose-block-randomized, double-blind, placebo-controlled, ascending single-dose, Phase I study was performed in healthy Korean male subjects assigned to receive 25, 50, 100, 200, 400, or 600 mg of LC15-0444 capsules. Blood and urine samples were collected up to 72 hours after administration. Plasma and urine drug concentrations were determined by tandem mass spectrometry coupled with high-performance liquid chromatography. DPP IV activity was measured by continuous spectrophotometric assay. An additional food effect study was performed in the 100-mg dose group; changes in PK and PD parameters after high-fat diet were evaluated. Adverse events (AEs) were detected through investigator inquiries, spontaneous reports, and clinical evaluations such as physical examinations, vital sign measurements, 12-lead electrocardiography, clinical laboratory tests (eg, hematology, blood chemistry, coagulation, urinalysis), and computerized impedance cardiography. RESULTS: Sixty Korean men (mean age, 25.3 years [range, 19-39 years]; weight, 68.3 kg [range, 53.6-84.9 kg]) were enrolled, providing 10 subjects for each dose group. After administration, LC15-0444 reached T(max) at 0.5 to 5.1 hours, and was eliminated with a t((1/2)) of 16.7 to 21.3 hours. The mean fraction of unchanged drug excreted in urine ranged from 0.21 to 0.34 and mean renal clearance was 15.5 to 23.6 L/h. The dose-normalized AUC exhibited dose-linearity over the range of 50 to 400 mg. All doses of LC15-0444 =200 mg were found to inhibit 80% of DPP IV activity for 24 hours. High-fat diet did not significantly influence the AUC of LC15-0444. LC15-0444 was generally well tolerated. None of the subjects developed any serious clinical or laboratory AEs or discontinued the study due to an AE. All AEs were mild or moderate, and no dose-related trends were observed. Forty-six AEs were reported in 18 subjects (30.0%). AEs considered to be related to the study drug were headache (6 cases), dizziness (2), nausea (1), epistaxis (1), and increased heart rate (1). All AEs resolved spontaneously. CONCLUSIONS: A single dose of LC15-0444 exhibited linear PK properties over the range of 50 to 400 mg in these healthy Korean male subjects. PK characteristics were not significantly influenced by food. In addition, doses >or=200 mg of LC15-0444 inhibited plasma DPP IV activity by >80% over a 24-hour dosing interval, and a 600-mg dose increased active glucagon-like peptide-1 levels after a standardized meal. LC15-0444 was generally well tolerated.

Experimental and QSAR studies on adsorptive interaction of anionic nonsteroidal anti-inflammatory drugs with activated charcoal.

Adsorptive interactions, namely adsorption capacity (qm) and affinity (b), between nonsteroidal anti-inflammatory drugs (NSAIDs) in anionic forms and commercial activated charcoal (AC), were estimated by isotherm experiment in a batch, and the properties were modeled based on the concept of quantitative structure-activity relationship (QSAR). Experimental results showed that AC had a high qm (0.38-0.67 mmol g-1) and b (14.03-930.8 L mmol-1) for the selected NSAIDs. In QSAR modeling, linear free energy relationship (LFER) descriptors of excess molar refraction (E), dipolarity/polarizability (S), and Coulombic interactions of anions (J-) were highly related to log qm, and the combination of the three terms could predict log qm in R2 of 0.97 and SE of 0.015 log unit. In the case of b, only single B term showed a good correlation with log b in R2 of 0.81. Additionally, the combination of hydrogen-bonding acceptors (HBAs) and molar volume (MV), which are easily calculable parameters, could also derive good predictability in R2 = 0.81 and SE = 0.26 log unit. Afterwards, validation of the QSAR models based on the leave-one-out cross-validation (Q2LOO) method showed that the models were acceptable.

Valorisation of post-sorption materials: Opportunities, strategies, and challenges.

Adsorption is a facile, economic, eco-friendly and low-energy requiring technology that aims to separate diverse compounds (ions and molecules) from one phase to another using a wide variety of adsorbent materials. To date, this technology has been used most often for removal/recovery of pollutants from aqueous solutions; however, emerging post-sorption technologies are now enabling the manufacture of value-added key adsorption products that can subsequently be used for (i) fertilizers, (ii) catalysis, (iii) carbonaceous metal nanoparticle synthesis, (iv) feed additives, and (v) biologically active compounds. These new strategies ensure the sustainable valorisation of post-sorption materials as an economically viable alternative to the engineering of other green chemical products because of the ecological affability, biocompatibility, and widespread accessibility of post-sorption materials. Fertilizers and feed additives manufactured using sorption technology contain elements such as N, P, Cu, Mn, and Zn, which improve soil fertility and provide essential nutrients to animals and humans. This green and effective approach to managing post-sorption materials is an important step in reaching the global goals of sustainability and healthy human nutrition. Post-sorbents have also been utilized for the harvesting of metal nanoparticles via modern catalytic pyrolysis techniques. The resulting materials exhibited a high surface area (>1000m2/g) and are further used as catalysts and adsorbents. Together with the above possibilities, energy production from post-sorbents is under exploration. Many of the vital 3E (energy, environment, and economy) problems can be addressed using post-sorption materials. In this review, we summarize a new generation of applications of post-adsorbents as value-added green chemical products. At the end of each section, scientific challenges, further opportunities, and issues related to toxicity are discussed. We believe this critical evaluation not only delivers essential contextual information to researchers in the field but also stimulates new ideas and applications to further advance post-sorbent applications.

Feasibility of full-spectrum endoscopy: Korea's first full-spectrum endoscopy colonoscopic trial.

AIM: To evaluate the full-spectrum endoscopy (FUSE) colonoscopy system as the first report on the utility thereof in a Korean population. METHODS: We explored the efficacy of the FUSE colonoscopy in a retrospective, single-center feasibility study performed between February 1 and July 20, 2015. A total of 262 subjects (age range: 22-80) underwent the FUSE colonoscopy for colorectal cancer screening, polyp surveillance, or diagnostic evaluation. The cecal intubation success rate, the polyp detection rate (PDR), the adenoma detection rate (ADR), and the diverticulum detection rate (DDR), were calculated. Also, the success rates of therapeutic interventions were evaluated with biopsy confirmation. RESULTS: All patients completed the study and the success rates of cecal and terminal ileal intubation were 100% with the FUSE colonoscope; we found 313 polyps in 142 patients and 173 adenomas in 95. The overall PDR, ADR and DDR were 54.2%, 36.3%, and 25.2%, respectively, and were higher in males, and increased with age. The endoscopists and nurses involved considered that the full-spectrum colonoscope improved navigation and orientation within the colon. No colonoscopy was aborted because of colonoscope malfunction. CONCLUSION: The FUSE colonoscopy yielded a higher PDR, ADR, DDR than did traditional colonoscopy, without therapeutic failure or complications, showing feasible, effective, and safe in this first Korean trial.

Preparation and Characterization of Composites Based on Polylactic Acid and Beeswax with Improved Water Vapor Barrier Properties.

UNLABELLED: Beeswax and a plasticizer (ATBC) were added to polylactic acid (PLA) films in order to enhance the water vapor barrier properties of the films. Beeswax improved the barrier properties; the water vapor permeability in the composite containing 1% beeswax was 58% lower than that of the neat PLA. Fourier transform infrared spectroscopy and X-ray diffraction analysis revealed that the incorporation of beeswax and ATBC had so little effect on the PLA structure. In addition, the structure of PLA did not vary substantially with the additions. The surfaces of the composites were examined by using field emission scanning electron microscopy. Differential scanning calorimetry results showed that the degree of crystallinity of the PLA films increased with the addition of beeswax and ATBC. However, the tensile strength and elongation at break of the composites containing beeswax were up to approximately 50% lower than those of the neat PLA. Although further study is needed to improve the mechanical properties, the aforementioned results showed that the PLA barrier properties can be improved by the incorporation of a small amount of beeswax and ATBC. PRACTICAL APPLICATION: The results of this study can be applied for the preparation of PLA composite films with improved barrier properties. Such biodegradable films are extremely useful for applications in the food packaging industry.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

BACKGROUND: In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. METHODS: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. RESULTS: The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. CONCLUSION: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Purification and some properties of a blue copper protein from Methylobacillus sp. strain SK1 DSM 8269.

A blue protein was purified from the Methylobacillus sp. strain SK1 that is grown on methanol in the presence of copper ion. This protein was found to be a monomer with a molecular weight of 13,500. The Isoelectric point of the protein was estimated to be 8.8. The spectrum of the protein that was treated with ferricyanide showed a broad peak around 620 nm, but that of the dithionite-treated protein revealed no peaks. It contained 0.83 mol of EDTA-stable copper per mol protein. Under air, the protein accelerated the inactivation of methanol dehydrogenase (MDH). The protein was reducible by phenazine methosulfate or by active MDH that was prepared from cells that were grown in the absence of added copper, but not by methanol, dichlorophenol indophenol, or inactive MDH that was prepared from cells that were grown in the presence of added copper. It was also reducible by active MDH in the presence of methanol. The absorption peak at 340 nm of the active MDH disappeared after the enzyme was treated with ferricyanide, hydrogen peroxide, or the purified blue protein. The inactive MDH also showed no peak at 340 nm. The 340-nm peak was not recovered after incubation of the inactive MDH and blue protein-treated active MDH with dithionite or methanol. The inactive MDH and blue protein-treated active MDH co-migrated with the active MDH preparation on nondenaturing polyacrylamide gel, and contained two non-identical subunits with molecular weights that were identical to those of the active MDH. The N-terminal amino acid sequence of the protein was Ala-Gly-Cys-Ser-Val-Asp-Val-Glu-Ala-Asn-Asp-Ala-Met-Gln-Phe. An analysis of the amino acid composition revealed that the protein contained no tryptophan. It contained three cysteines per mol protein. The blue protein in Methylobacillus sp. strain SK1 was produced only in the cells that were grown in the copper-supplemented medium.

Pharmacokinetic and pharmacodynamic interaction between gemigliptin and metformin in healthy subjects.

BACKGROUND AND OBJECTIVE: Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability. METHODS: A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence crossover study was conducted in healthy male subjects. Twenty-seven subjects received gemigliptin (50 mg once daily), metformin (1,000 mg twice a day), or both drugs for 7 days per dosing period. Blood samples were drawn over 24 h on the seventh day of each period for pharmacokinetic and pharmacodynamic evaluations, including plasma DPP-4 activity and total/active glucagon-like peptide-1 (GLP-1) levels. Meal tolerance tests were conducted for pharmacodynamic assessment on the eighth day. Safety and tolerability were evaluated using adverse events, vital signs, ECGs, and clinical laboratory tests. RESULTS: Coadministration of gemigliptin and metformin had no significant effect on the pharmacokinetics of gemigliptin or metformin. The inhibition of DPP-4 by gemigliptin was not affected by coadministration with metformin. Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels. The plasma glucagon level was lower in co-therapy than with metformin monotherapy. The coadministration of gemigliptin and metformin was well-tolerated without serious adverse events. CONCLUSIONS: Coadministration of gemigliptin and metformin showed beneficial anti-diabetic effects without pharmacokinetic drug-drug interactions.

δ-Catenin overexpression promotes angiogenic potential of CWR22Rv-1 prostate cancer cells via HIF-1α and VEGF.

This study revealed that CWR22Rv-1 cells overexpressing δ-catenin display bigger tumor formation and higher angiogenic potentials than their matched control cells in the CAM assay. In addition, δ-catenin overexpression in CWR22Rv-1 cells results in increased hypoxia-inducible factor 1-alpha (HIF-1α and vascular endothelial growth factor (VEGF) expression. Furthermore, δ-catenin overexpression was found to enhance nuclear distribution of both ß-catenin and HIF-1α in hypoxic condition, which is diminished by knockdown of δ-catenin. Our current study adds novel evidence regarding contribution of δ-catenin to the progression of prostate cancer.