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Ever since bioplastics were introduced to a wide range of industries globally, disposal of the used bioplastics has become an inseparable issue with their application. Unlike petroleum-based plastics, bioplastics can be completely decomposed into water and carbon dioxide by microorganisms in a relatively short time, which is an advantage. However, there is little information on the specific degraders and accelerating factors for biodegradation. To elucidate a new strain for biodegradation of poly-3-hydroxybutyrate (PHB), we screened out one PHB-degrading bacterium, Microbulbifer sp. SOL03, which is the first reported strain from the Microbulbifer genus to show PHB degradation activity, although Microbulbifer species are known to be complex carbohydrate degraders found in high-salt environments. In this study, we evaluated its biodegradability using solid- and liquid-based methods in addition to examining the changes in physical properties throughout the biodegradation process. Furthermore, we established the optimal conditions for biodegradation with respect to temperature, salt concentration, and additional carbon and nitrogen sources; accordingly, a temperature of 37°C with the addition of 3% NaCl without additional carbon sources, was determined to be optimal. In summary, we found that Microbulbifer sp. SOL03 showed a PHB degradation yield of almost 97% after 10 days. To the best of our knowledge, this is the first study to investigate the potent bioplastic degradation activity of Microbulbifer sp., and we believe that it can contribute to the development of bioplastics from application to disposal.

Phasin (PhaP), one of the polyhydroxyalkanoate granule-associated protein, enhances cell growth and polyhydroxybutyrate (PHB) biosynthesis by regulating the number and size of PHB granules. However, few studies have applied phasins to various PHB production conditions. In this study, we identified novel phasin genes from the genomic data of Arctic soil bacterium Pseudomonas sp. B14-6 and determined the role of phaP1Ps under different PHB production conditions. Transmission electron microscopy and gel permeation chromatography revealed small PHB granules with high-molecular weight, while differential scanning calorimetry showed that the extracted PHB films had similar thermal properties. The phasin protein derived from Pseudomonas sp. B14-6 revealed higher PHB production and exhibited higher tolerance to several lignocellulosic biosugar-based inhibitors than the phasin protein of Ralstonia eutropha H16 in a recombinant Escherichia coli strain. The increased tolerance to propionate, temperature, and other inhibitors was attributed to the introduction of phaP1Ps, which increased PHB production from lignocellulosic hydrolysate (2.39-fold) in the phaP1Ps strain. However, a combination of phasin proteins isolated from two different sources did not increase PHB production. These findings suggest that phasin could serve as a powerful means to increase robustness and PHB production in heterologous strains.

BACKGROUND Previous research has not evaluated the potential effect of transversus abdominis plane (TAP) block on quality of recovery following laparoscopic cholecystectomy. Therefore, we investigated whether addition of the bilateral subcostal and lateral TAP (bilateral dual TAP [BD-TAP]) blocks to multimodal analgesia would improve the quality of recovery as assessed with the Quality of Recovery-40 (QoR-40). METHODS Patients age 18 to 60 years who were scheduled to undergo elective laparoscopic cholecystectomy were randomized to the BD-TAP or control group. The BD-TAP group received the BD-TAP block with multimodal analgesia under general anesthesia, using 0.25% ropivacaine, and the control group was treated with the same method, except that they received the sham block using 0.9% normal saline. Both groups had the same multimodal analgesia regimen, consisting of intravenous dexamethasone, propacetamol, ibuprofen, and oxycodone. The primary outcome was the QoR-40 score at 24 hours after surgery. Data were analyzed using the independent t test, Mann-Whitney U test, χ2 test, and Fisher exact test. RESULTS Thirty-eight patients in each group were recruited. The mean QoR-40 score decreased by 13.6 (95% confidence interval [CI], 8.3-18.8) in the BD-TAP group and 15.6 (95% CI, 6.7-24.5) in the control group. The postoperative QoR-40 score at 24 hours after surgery did not differ between the 2 groups (BD-TAP group, median [interquartile range], 170.5 [152-178]; control group, 161 [148-175]; median difference, 3 [95% CI, -5 to 13]; P = .427). There were no differences between the 2 groups in the pain dimension of the QoR-40: 30.5 (95% CI, 27-33) in the BD-TAP group and 31 (95% CI, 26-32) in the control group; median difference was 0 (95% CI, -2 to 2); P = .77. CONCLUSIONS Our results indicate that the BD-TAP block does not improve the quality of recovery or analgesic outcomes following laparoscopic cholecystectomy. Our results do not support the routine use of the BD-TAP block for this surgery.

Whole-cell systems offer many benefits for biochemical production, such as relatively easy enzyme control and higher tolerance toward harsh environments, than purified enzymes. These systems can be applied to many bioconversion reactions, but they sometimes require cofactor regeneration units to support reactions at high substrate concentrations. Here, we examined l-glutamate oxidase (GOX) from Streptomyces sp. X119-6, which produces α-ketoglutarate (α-KG) from l-glutamate, and catalase (KatE) from Escherichia coli, which removes hydrogen peroxide generated by GOX. After optimizing the expression vector, pH, strains, culture conditions, and isopropyl β-d-1-thiogalactopyranoside concentration, we compared their efficiency to that of a previously reported GOX from Streptomyces mobaraensis. Our results indicated that GOX from Streptomyces sp. X119-6 and KatE increased α-KG production by 2.76-fold. This GOX required high levels of α-KG as an amino donor to convert 5-aminovaleric acid to glutaric acid. Performing the reaction at pH 8 enabled us to avoid the exogenous addition of catalase, but severe substrate inhibition was observed, resulting in the production of 287 mM glutaric acid. This α-KG regeneration system has potential for improving production in various aminotransferase systems.

Polyhydroxybutyrate (PHB) is a biodegradable plastic with physical properties similar to petrochemically derived plastics. Here, Shewanella marisflavi BBL25 was engineered by inserting the pLW487 vector containing polyhydroxyalkanoates synthesis genes from Ralstonia eutropha H16. Under optimal conditions, the engineered S. marisflavi BBL25 produced 1.99 ± 0.05 g/L PHB from galactose. The strain showed high tolerance to various inhibitors and could utilize lignocellulosic biomass for PHB production. When barley straw hydrolysates were used as a carbon source, PHB production was 3.27 ± 0.19 g/L. In addition, PHB production under the microbial fuel cell system was performed to confirm electricity coproduction. The maximum electricity current output density was 1.71 mA/cm2, and dry cell weight (DCW) and PHB production were 11.4 g/L and 6.31 g/L, respectively. Our results demonstrated PHB production using various lignocellulosic biomass and the feasibility of PHB and electricity production, simultaneously, and it is the first example of PHB production in engineered Shewanella.

Polyhydroxybutyrate (PHB) is a biodegradable plastic that can be used as an alternative to petrochemical-based plastics. PHB is produced by various microorganisms such as Ralstonia, Halomonas, and Bacillus species. However, there are very few strains that produce PHB using xylose, an abundant and inexpensive carbon source. In this study, ten xylose-utilizing PHB producers isolated from South Korean marine environments were screened and characterized. Among these isolates, Bacillus sp. SM01, a newly identified strain, produced the highest amount of PHB using xylose. Under optimal conditions, the maximum dry cell weight (DCW) was 3.41 ± 0.09 g/L, with 62% PHB content, and Bacillus sp. SM01 showed Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer production with propionate; however, the growth of Bacillus sp. SM01 was greatly inhibited by the presence of glucose. Co-culturing Bacillus sp. SM01 with Cupriavidus necator NCIMB 11599 resulted in increased DCW, PHB production, and utilization of glucose and xylose, the main sugar of lignocellulosic biomass, compared with the monoculture. Our results indicated that this co-culture system can be used to increase PHB production and overcome the limitation of sugar consumption associated with Bacillus sp. SM01 and C. necator.

Among various species of marine bacteria, those belonging to the genus Halomonas have several promising applications and have been studied well. However, not much information has been available on their antibiotic resistance. In our efforts to learn about the antibiotic resistance of strain Halomonas socia CKY01, which showed production of various hydrolases and growth promotion by osmolytes in previous study, we found that it exhibited resistance to multiple antibiotics including kanamycin, ampicillin, oxacillin, carbenicillin, gentamicin, apramycin, tetracycline, and spectinomycin. However, the H. socia CKY01 resistance pattern to kanamycin, gentamicin, apramycin, tetracycline, and spectinomycin differed in the presence of 10% NaCl and 1% NaCl in the culture medium. To determine the mechanism underlying this NaCl concentration-dependent antibiotic resistance, we compared four aminoglycoside resistance genes under different salt conditions while also performing time-dependent reverse transcription PCR. We found that the aph2 gene encoding aminoglycoside phosphotransferase showed increased expression under the 10% rather than 1% NaCl conditions. When these genes were overexpressed in an Escherichia coli strain, pETDuet-1::aph2 showed a smaller inhibition zone in the presence of kanamycin, gentamicin, and apramycin than the respective control, suggesting aph2 was involved in aminoglycoside resistance. Our results demonstrated a more direct link between NaCl and aminoglycoside resistance exhibited by the H. socia CKY01 strain.

NiO nanoparticle (NP)-functionalized nanograined ZnO nanorods (NRs) were grown by using the thermal evaporation of ZnSe powders; this was followed by the thermal oxidation of the ZnSe NRs to synthesize ZnO NRs and a solvothermal process for NiO functionalization. The diameters of the grains in the synthesized nanograined ZnO NRs are in the range of 50–150 nm. The ZnO grains were not spherical, but they were shaped like rice grains. The diameters and the lengths of the ZnO NRs were in the range of 40–50 nm and 1–6 µm, respectively. The diameters of the NiO NPs were in the range of 40–80 nm. A multiple-networked chemiresistive sensor was fabricated by pouring the IPA solution containing NiO NP-decorated nanograined ZnO NRs onto SiO2/Si substrates with a patterned electrode. A pristine nanograined ZnO NR sensor was also prepared in a similar manner. The NiO NP-functionalized nanograined ZnO NR sensor exhibited a greater and faster response to H2, as compared to its pristine nanograined ZnO counterpart; it also showed higher selectivity toward H2 against other reducing gases, as compared to the pristine nanograined ZnO counterpart. Herein, the origin of the enhanced sensing performance of the NiO NP-functionalized nanograined ZnO sensor is discussed in detail.

Cholangiocarcinoma (CCA) has a poor prognosis and high chemoresistance. Interleukin-4 receptor (IL-4R) is overexpressed in several cancer cells and plays a crucial role in tumor progression and drug resistance. IL4RPep-1, an IL-4R-binding peptide, has been identified by phage display and used for tumor targeting. In this study, we exploited IL4RPep-1 to guide the tumor-specific delivery of a proapoptotic peptide to chemoresistant CCA, thereby inhibiting tumor growth. Immunohistochemistry of human primary CCA tissues showed that IL-4R levels were upregulated in moderately to poorly differentiated types, and higher levels of IL-4R are correlated with lower survival rates in patients with CCA. IL4RPep-1 was observed to preferentially bind with high IL-4R-expressing KKU-213 human CCA cells, whereas it barely bound with low IL-4R-expressing KKU-055 cells. A hybrid of IL4RPep-1 and a proapoptotic peptide (KLAKLAK)2 (named as IL4RPep-1-KLA) induced cytotoxicity and apoptosis in KKU-213 cells and increased those levels induced by 5-fluorouracil (5-FU). IL4RPep-1-KLA was internalized in the cells and colocalized with mitochondria. Whole-body fluorescence imaging and immunohistochemical analysis of tumor tissues showed the homing of IL4RPep-1-KLA as well as IL4RPep-1 to KKU-213 tumor in mice. Systemic administration of IL4RPep-1-KLA efficiently inhibited KKU-213 tumor growth, whereas treatment with 5-FU alone did not significantly inhibit tumor growth in mice. No significant systemic side effects including liver toxicity and immunotoxicity were observed in mice during peptide treatments. These findings suggest that IL4RPep-1-KLA holds potential as a targeted therapeutic agent against chemoresistant CCA.

Soil loss by rainfall is a serious problem in civil and environmental engineering. In this study, microbially induced calcite precipitation (MICP) was applied to reduce rainfall-induced soil loss. Furthermore, the effects of particle size and organic matter content were investigated. A mixture of Sporosarcina pasteurii, 450 mM urea, and 450 mM calcium ions was introduced to sand and sandy loam with 2.6% organic matter content to induce MICP. Artificial rainfall and penetrometer tests were conducted to analyze the soil loss and surface strength, respectively, of the MICP-applied soils. As MICP was applied, the concentration of CaCO3 precipitates increased linearly (9.8 mg CaCO3/g-soil/application), but the strength of the soil reached a plateau of 23.9 ± 1.2 N/mm after five repeated applications (54.5 ± 3.6 mg CaCO3/g-soil). Only after two repeated MICP applications, up to 84% of reduction in loss rate was accomplished in sand under the worst conditions (rainfall intensity of 75 mm/h, slope of 15°), while only 58% of reduction was obtained after five repeated applications in sandy loam with 2.6% organic matter. For the same amount of CaCO3 precipitates, the strength was higher in sand with larger particle size. Lower organic matter content led to the higher strength. SEM revealed that larger CaCO3 precipitates were obtained in sand with lower organic matter content. Our results indicate that the effect of MICP on the prevention of rainfall-induced soil loss is promoted when the particle size is larger and organic matter content is lower.

Carbonate treatment was tested as a means to mitigate the generation of alkaline leachate from basic oxygen furnace (BOF) slag. BOF slag was treated with 0.1, 0.5, and 1.0 M concentrations of NaHCO3 solution for 48 h at a liquid/solid ratio of 5 L/kg. At 1.0 M NaHCO3, the pH of the leachate decreased from 12.0 to 11.3 because less free CaO was dissolved from the treated slag. Approximately 1.59 mg-Ca2+/g-slag of free CaO was dissolved from the untreated BOF slag while only 0.06 mg-Ca2+/g-slag was liberated from the treated slag. When the data from X-ray photoelectron spectroscopy and thermogravimetric analysis were taken together, formation of CaCO3 precipitates on the surface of the treated BOF slag was evident. Surface precipitation of CaCO3 was more pronounced when CO2 gas was used as an alternative carbonate source. Carbon dioxide treatment further decreased the leachate pH to 8.3, probably because it liberated more Ca2+ from BOF slag during the treatment than 1.0 M NaHCO3 solution due to the pH difference (pH 6.6 and 9.6, respectively), in turn generating more CaCO3 precipitates. Scanning electron microscopy analysis revealed that more CaCO3 was precipitated on the CO2 gas-treated slag surface than on the NaHCO3-treated slag. This study identifies the leachate pH reduction-mechanism and the effect of carbonate source which are expected to contribute to the environmentally safe management of BOF slags.

Cathepsin K is highly expressed in various types of cancers. However, the effect of cathepsin K inhibition in cancer cells is not well characterized. Here, cathepsin K inhibitor (odanacatib; ODN) and knockdown of cathepsin K (siRNA) enhanced oxaliplatin-induced apoptosis in multiple cancer cells through Bax upregulation. Bax knockdown significantly inhibited the combined ODN and oxaliplatin treatment-induced apoptotic cell death. Stabilization of p53 by ODN played a critical role in upregulating Bax expression at the transcriptional level. Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. Interestingly, ODN-induced p53 and Bax upregulation were modulated by the production of mitochondrial reactive oxygen species (ROS). Mitochondrial ROS scavengers prevented OTUB1-mediated p53 stabilization and Bax upregulation by ODN. These in vitro results were confirmed by in mouse xenograft model, combined treatment with ODN and oxaliplatin significantly reduced tumor size and induced Bax upregulation. Furthermore, human renal clear carcinoma (RCC) tissues revealed a strong correlation between phosphorylation of OTUB1(Ser16) and p53/Bax expression. Our results demonstrate that cathepsin K inhibition enhances oxaliplatin-induced apoptosis by increasing OTUB1 phosphorylation via CK2 activation, thereby promoting p53 stabilization, and hence upregulating Bax.

This paper presents the development of the JET humanoid robot, which is based on the existing THORMANG platform developed in 2015. Application in the industrial and service fields was targeted, and three design concepts were determined for the humanoid robot. First, low stiffness of the actuator modules was utilized for compliance with external environments. Second, to maximize the robot whole-body motion capability, the overall height was increased. However, the weight was reduced to satisfy power requirements. The workspace was also increased to enable various postures, by increasing the range of motion of each joint and extending the links. Compared to the original THORMANG platform, the lower limb length increased by approximately 20%, and the hip range of motion increased by 39.3%. Third, the maintenance process was simplified through modularization of the electronics and frame design for improved accessibility. Several experiments, including stair climbing and egress from a car, were performed to verify that the JET humanoid robot performance enhancements reflected the design concepts.

In this study, a newly isolated halotolerant strain Oceanisphaera arctica YHY1, capable of hydrolyzing seafood processing waste chitin biomass, is reported. Microbial fuel cells fed with 1% chitin and 40 g L−1 as the optimum salt concentration demonstrated stable electricity generation until 216 h (0.228 mA/cm2). N-acetyl-D-glucosamine (GlcNAc) was the main by-product in the chitin degradation, reaching a maximum concentration of 192.01 mg g−1 chitin at 120 h, whereas lactate, acetate, propionate, and butyrate were the major metabolites detected in the chitin degradation. O. arctica YHY1 utilized the produced GlcNAc, lactate, acetate, and propionate as the electron donors to generate the electric current. Cyclic voltammetry (CV) investigation revealed the participation of outer membrane-bound cytochromes, with extracellular redox mediators partly involved in the electron transfer mechanism. Furthermore, the changes in structural and functional groups in chitin after degradation were analyzed using FTIR and XRD. Therefore, the ability of O. arctica YHY1 to utilize waste chitin biomass under high salinities can be explored to treat seafood processing brine or high salt wastewater containing chitin with concurrent electricity generation.

Engineered aluminum oxide nanoparticles (Al2 O3 NPs) having high-grade thermal stability and water-dispersion properties are extensively used in different industries and personal care products. Toxicological response evaluation of these NPs is indispensable in assessing the health risks and exposure limits because of their industrial disposal into the aquatic environment. We assessed and compared the developmental toxicity of Al2 O3 NPs in Xenopus laevis and Danio rerio over a period of 96 h using the frog embryo teratogenic assay Xenopus and a fish embryo toxicity assay. Engineered Al2 O3 NP exposure produced dose-dependent embryonic mortality and decreased the embryo length, indicating a negative effect on growth. Moreover, Al2 O3 NPs induced various malformations, such as small head size, a bent/deformed axis, edema, and gut malformation, dose-dependently and altered the expression of heart- and liver-specific genes in both X. laevis and D. rerio, as revealed by whole-mount in-situ hybridization and reverse transcriptase polymerase chain reaction. In conclusion, the toxicological data suggest that Al2 O3 NPs are developmentally toxic and teratogenic and negatively affect the embryonic development of X. laevis and D. rerio. Our study can serve as a model for the toxicological evaluation of nanomaterial exposure on vertebrate development that is critical to ensure human and environmental safety. Environ Toxicol Chem 2019;38:2672-2681. © 2019 SETAC.

[Purpose] Recent studies suggest that ursolic acid (UA) is a potential candidate for a resistance exercise mimetic that can increase muscle mass and alleviate the deleterious effect of skeletal muscle atrophy on bone health. However, these studies evaluated the effects of UA on skeletal muscle and bone tissues, and they have not verified whether such effect could occur concurrently on muscle and bone, as is the case with resistance exercise. Thus, the aim of this study was to analyze the effect of UA injection on muscle mass and bone microstructure using an animal model of atrophy to demonstrate the potential of UA as a resistance exercise mimetic. [Methods] The immobilization (IM) method was used on the left hindlimb of Sprague Dawley (SD) rats for 10 days to induce muscle atrophy, whereas the right hindlimb was used as an internal control (IC). The animal models were divided into two groups, SED (sedentary, n=6) and UA (n=6) to demonstrate the effect of UA on atrophic skeletal muscles. The UA group received a daily intraperitoneal injection of UA (5 mg/kg/day) for 8 weeks. After 10 days of IM, the data collected for the IC were compared with that of IM to determine whether muscle atrophy might occur. [Results] Muscle atrophy was induced and bone mineral density (BMD) decreased significantly. The 8-week UA treatment significantly increased the gastrocnemius muscle mass compared to the SED group. In regard to the effect of UA on bones, negative results such as a decrease in BMD, trabecular bone volume fraction, and trabecular number, and an increase in trabecular separation, were observed in the SED group, but no such difference was observed in the UA group. No significant difference was observed in atrophic hindlimbs between SED and UA groups. [Conclusion] These results alone are insufficient to suggest that UA is a potential resistance exercise mimetic for atrophic skeletal muscle and weakened bone. However, this study will help determine the potential of UA as a resistance exercise mimetic.

Hyaluronidases enhance therapeutic drug transport by breaking down the hyaluronan barrier to lymphatic and capillary vessels, facilitating their tissue absorption. Commercially available hyaluronidases are bovine in origin; however, they pose risks such as bovine spongiform encephalopathy. The present study aimed to develop a novel, highly active hyaluronidase and assess its function. Therefore, in order to find the most efficient active hyaluronidase, we produced several shortened hyaluronidases with partial removal of the N- or C-terminal regions. Moreover, we created an enzyme that connected six histidines onto the end of the hyaluronidase C-terminus. This simplified subsequent purification using Ni2+ affinity chromatography, making it feasible to industrialize this highly active recombinant hyaluronidase which exhibited catalytic activity equal to that of the commercial enzyme. Therefore, this simple and effective isolation method could increase the availability of recombinant hyaluronidase for research and clinical purposes.

Background We assessed the frequency and severity of hypoglycemia in type 2 diabetes mellitus patients treated with sulfonylurea monotherapy or sulfonylurea+metformin. Methods We conducted a retrospective, observational, cross-sectional study in 2011 and 2012 including patients with type 2 diabetes mellitus aged ≥30 years who were treated with ≥6 months of sulfonylurea monotherapy or sulfonylurea+metformin at 20 university-affiliated hospitals in Korea. At enrollment, glycated hemoglobin (HbA1c) was assessed; participants completed self-reported questionnaires describing hypoglycemia incidents over the past 6 months. A review of medical records up to 12 months before enrollment provided data on demographics, disease history, comorbidities, laboratory results, and drug usage. Results Of 726 enrolled patients, 719 were included (55.6% male); 31.7% and 68.3% were on sulfonylurea monotherapy and sulfonylurea+metformin, respectively. Mean±standard deviation age was 65.9±10.0 years; mean HbA1c level was 7.0%±1.0%; 77.8% of patients had hypertension (89.4% used antihypertensive medication); 60.5% had lipid disorders (72.5% used lipid-lowering medication); and 52.0% had one or more micro- or macrovascular diseases. Among patients with A1c measurement (n=717), 56.4% achieved therapeutic goals (HbA1c

Purpose Dexamethasone (Dex) has long been used as a potent immunosuppressive agent in the treatment of inflammatory and autoimmune diseases, despite serious side effects. In the present study, Dex and model antigen ovalbumin (OVA) were encapsulated with poly(lactic-co-glycolic acid) to deliver Dex and OVA preferentially to phagocytic cells, reducing systemic side effects of Dex. The OVA-specific immune tolerance-inducing activity of the nanoparticles (NPs) was examined. Methods Polymeric NPs containing OVA and Dex (NP[OVA+Dex]) were prepared by the water-in-oil-in-water double emulsion solvent evaporation method. The effects of NP[OVA+Dex] on the maturation and function of immature dendritic cells (DCs) were examined in vitro. Furthermore, the OVA-specific immune tolerizing effects of NP[OVA+Dex] were confirmed in mice that were intravenously injected or orally fed with the NPs. Results Immature DCs treated in vitro with NP[OVA+Dex] did not mature into immunogenic DCs but instead were converted into tolerogenic DCs. Furthermore, profoundly suppressed generation of OVA-specific cytotoxic T cells and production of OVA-specific IgG were observed in mice injected with NP[OVA+Dex], whereas regulatory T cells were concomitantly increased. Feeding of mice with NP[OVA+Dex] also induced OVA-specific immune tolerance. Conclusion The present study demonstrates that oral feeding as well as intravenous injection of poly(lactic-co-glycolic acid) NPs encapsulating both antigen and Dex is a useful means of inducing antigen-specific immune tolerance, which is crucial for the treatment of autoimmune diseases.

Leptin, a hormone primarily derived from adipose tissue, is known to induce tumor growth, but its underlying mechanisms of action are not clearly understood. Inflammasomes, acting as signaling platforms for controlling inflammatory responses, modulate tumor growth in a complicated manner. In this study, we investigated the role of inflammasomes in leptin-induced growth of breast cancer cells. Herein, we showed that leptin activated NLRP3 inflammasomes in MCF-7 breast cancer cells, as determined by activation of caspase-1, maturation of interleukin-1β, and increased expression of the inflammasome components, including NLRP3 and ASC. Interestingly, inhibition of the inflammasome by treatment with a pharmacological inhibitor of caspase-1 or gene silencing of NLRP3 prevented leptin-induced increase in cell viability. Moreover, suppression of apoptosis and cell cycle promotion by leptin were also significantly abolished by gene silencing of NLRP3, clearly indicating a crucial role of NLRP3 inflammasomes in leptin-induced breast cancer growth. In addition, inhibition of estrogen receptor signaling or ROS production markedly blocked leptin-induced activation of NLRP3 inflammasomes, suggesting that estrogen receptor signaling and ROS production mediate inflammasomes activation by leptin. The stimulatory effect of leptin on inflammasomes activation was also observed in MCF-7 tumor xenograft model. Furthermore, the critical roles of inflammasomes activation in leptin-induced tumor growth, suppression of apoptotic gene expression, and induction of the genes stimulating cell cycle were confirmed in a tumor xenograft model. Taken together, these results demonstrate that inflammasomes activation plays a pivotal role in leptin-induced growth of breast cancer cells via modulation of both apoptosis and cell cycle.

Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle ­harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.

Specialized proresolving mediators are enzymatically oxygenated natural molecules derived from polyunsaturated fatty acids and are considered novel. These novel mediators include lipoxins from arachidonic acid, resolvins and protectins from omega-3 essential fatty acids, and new maresins. These mediators harbor potent dual proresolving and anti-inflammatory properties. Resolvins and protectins are known to be potent when administered to various inflammation-associated animal models of human diseases. Although psoriasis' etiology remains unknown, there is accumulating evidence indicating that cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-23, and IL-17, play pivotal roles in its development. Experimentally, resolvins, maresins, and lipoxins downregulate the cytokine expression of the IL-23/IL-17 axis and inhibition of mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) cell signaling transduction pathways. Here, we assessed the effects of protectin D1 (PD1) on imiquimod (IMQ)-induced psoriasiform skin inflammation and keratinocytes. PD1 showed clinical improvement in skin thickness, redness, and scaling in psoriasis mouse models. Moreover, PD1 decreased IL-1β, IL-6, IL-17, and CXCL1 mRNA expressions and reduced STAT1 and NF-κB signaling pathway activation in lesions. Serum myeloperoxidase, IgG2a, IL-1β, IL-6, IL-17, and TNF-α and spleen CD4+IFN-γ+IL-17+ T lymphocytes were reduced after PD1 treatment in IMQ-induced psoriasiform mouse models. In addition, IL-1β, IL-6, IL-8, and IL-18BP gene expressions were decreased in PD1-treated keratinocytes. Moreover, a decrease in the expression levels of CCL17 and IL-6 and an inhibition of the STAT1 and NF-κB signaling transduction pathways was observed in keratinocytes. These PD1 anti-inflammatory effects suggest that it is a good therapeutic candidate for psoriasis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects 10-20% of the world's population. Therefore, the discovery of drugs for the treatment of AD is important for human health. Hispidulin (HPD; also known as scutellarein 6-methyl ether or dinatin) is a natural flavone that exerts anti-inflammatory effects. In the present study, the effectiveness of HPD on AD-like skin inflammation was investigated. We used a mouse AD model through repeated exposure of mice to 2,4-dinitrochlorobenzene and house dust mite extract (Dermatophagoides farinae extract, DFE) to the ears. In addition, tumor necrosis factor-α and interferon-γ-activated keratinocytes (HaCaT cells) were used to investigate the underlying mechanism of HPD action. Oral administration of HPD alleviated AD-like skin inflammations: it reduced ear thickness; serum immunoglobulin (Ig)E, DFE-specific IgE, and IgG2a levels; and inflammatory cell infiltration. HPD reduced the expression of pro-inflammatory cytokines and chemokines through inhibition of signal transducer and activator of transcription 1 nuclear factor-κB in HaCaT cells. Taken together, these results suggest that HPD could be a potential drug candidate for the treatment of AD.

Aims In this study, we integrated two randomized control trials, PROSPECTIVE and IMPACT, to address the effect of probucol on cerebrocardiovascular events and carotid intima-media thickness (IMT) in Japanese, Korean, and Chinese patients with coronary artery disease (CAD). Methods A total of 1,025 patients from the PROSPECTIVE and IMPACT studies were enrolled. The time to the first major adverse cerebrocardiovascular event, in addition to carotid IMT and lipid levels, was compared between the control and probucol groups. Results In the integrated analysis, the adjusted hazard ratio (HR) and 95% confidence interval (CI) were 0.67 and 0.44-1.03, respectively, indicating a tendency to show the effect of probucol on cerebrocardiovascular events in secondary prevention. We also found no significant differences between the control and probucol groups in the mean IMT of the carotid arteries and its changes. However, we found a significant decrease in cerebrocardiovascular events in patients with reduced levels of HDL cholesterol (HDL-C) (≥ 6.25 mg/dL) compared with those with levels ＜6.25 mg/dL (p=0.024), without any increase in adverse events such as severe ventricular arrhythmias. Conclusion We demonstrated a marginal effect of probucol on cerebrocardiovascular events in Asian patients with CAD, with reasonable safety profiles. A larger study may be needed to support the effect of probucol for cardiovascular prevention.

MR images based on phase contrast images have gained clinical interest as an in vivo tool for assessing anatomical and histological findings. The globus pallidus is an area of major iron metabolism and storage in the brain tissue. Calcium, another important metal in the body, is frequently deposited in the globus pallidus as well. Recently, we observed dense paramagnetic deposition with paradoxical calcifications in the globus pallidus and putamen. In this work, we explore detailed MR findings on these structures, and the histological source of the related findings using ex vivo CT and MR images. Ex vivo MR was obtained with a maximum 100 μm3 isotropic resolution using a 15.2 T MR system. 3D gradient echo images and quantitative susceptibility mapping were used because of their good sensitivity to metallic deposition, high signal-to-noise ratio, and excellent contrast to iron and calcium. We found dense paramagnetic deposition along the perforating arteries in the globus pallidus. This paramagnetic deposition was hyperdense on ex vivo CT scans. Histological studies confirmed this finding, and simultaneous deposition of iron and calcium, although more iron dominant, was observed along the vessel walls of the globus pallidus. This was an exclusive finding for the penetrating arteries of the globus pallidus. Thus, our results suggest that several strong and paradoxical paramagnetic sources at the globus pallidus can be associated with vascular degeneration.

The plasma proteins around nanoparticles (NPs) form an outer protein corona, significantly influencing the subsequent immune response. However, it was uncertain whether the protein corona around NPs influences immune response. This study clarified that the immune response mediated by the protein corona is greatly dependent on the type of plasma proteins surrounding the NPs. Structural changes in the unfolded protein corona elevated reactive oxygen species (ROS) levels and induced major proinflammatory cytokine release in both murine and human macrophage cell lines. In contrast, negligible structural changes in the protein corona provoke neither ROS production nor proinflammatory cytokine release. Furthermore, in vivo analysis confirms that a stimulated immune response by an unfolded protein corona triggers selective activation of innate and adaptive immunity in the spleen. Specifically, neutrophils, natural killer cells, and CD8+ T cells are overpopulated by unfolded protein corona structures surrounding nanotubes, whereas innate and adaptive immunologic responses are not triggered by a normal protein corona. In conclusion, highly unfolded protein corona structures are strongly correlated with subsequent activation of proinflammatory cytokines and innate immune responses; thus, the protein corona can be used in immune‐enhancing therapy., Schematic images illustrating structural changes in the plasma protein (unfolded) surrounding the nanotube that elicit innate and adaptive immune responses. Plasma proteins with a native structures surrounding nanotube did not induce immune responses.

SG-SP1, a newly synthesised gallic acid derivative, blocks histamine release by reducing calcium influx in mast cells and inhibits inflammatory cytokine expression. This derivative has promising anti-allergic potential. Our research was designed to establish a quantitative determination method for SG-SP1 in rat plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability and to characterise its pharmacokinetic behaviour in rats. After simple protein precipitation with acetonitrile including an internal standard, SG-SP1 was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (2:8 v/v, including 0.1 % formic acid). The protonated precursor ion [M+H]+ and major fragment ion were confirmed at m/z 588.2 and 180.1, respectively. The substance was stable under bench and storage conditions. The analytical method met the criteria of FDA-validated bioanalytical methods and was successfully applied to a pharmacokinetic study for the first time. SG-SP1 decayed in a biphasic pattern with terminal half-life of 5.1 h and clearance of about 3.2 L/h/kg. Double peaks were observed following oral administration, and the absolute oral bioavailability was ∼1 %.

Polyhydroxyalkanoates (PHAs) are bioplastic substitutes for petroleum-derived plastics that may help to reduce the increasing environmental impact of plastic pollution. Among them, polyhydroxybutyrate (PHB) is a promising biopolymer, incentivizing many researchers to search for PHB-producing and PHB-degrading bacteria for improved PHB utilization. Many novel PHB-producing microorganisms have been discovered; however, relatively few PHB-degrading bacteria have been identified. Six PHB-degrading bacteria were found in marine soil and investigated their PHB-degrading abilities under various temperature and salinity conditions using solid-media based culture. Finally, thermotolerant and halotolerant PHB-degrader Bacillus sp. JY14 was selected. PHB degradation was confirmed by monitoring changes in the physical and chemical properties of PHB films incubated with Bacillus sp. JY14 using scanning electron microscopy, Fourier-transform infrared spectroscopy, and gel permeation chromatography. Further, PHB degradation ability of Bacillus sp. JY14 was measured in liquid culture by gas chromatography. After 14 days of cultivation with PHB film, Bacillus sp. JY14 achieved approximately 98% PHB degradation. Applying various bioplastics to assess the bacteria's biodegradation capabilities, the result showed that Bacillus sp. JY14 could also degrade P(3HB-co-4HB) and P(3HB-co-3HV). Overall, this study identified a thermotolerant and halotolerant bacteria capable of PHB degradation under solid and liquid conditions. These results suggest that this bacteria could be utilized to degrade various PHAs.

Reinforced concrete (RC) structures age with time, which results in performance degradation and cracks. These performance degradations do not recover easily, but a performance higher than the existing structures can be expected through reinforcement. There are various reinforcement methods for RC structures. This study selected four reinforcement methods: near-surface mounting (NSM), external prestressing (EP), external bonding (EB), and section enlargement (SE). In the past, steel bars were often used as reinforcements. However, this study uses fiber-reinforced polymer (FRP), which is an alternative to steel bars owing to its high tensile strength, and its non-corrosive and lightweight properties. It is a basic strengthening material, along with a carbon-fiber-reinforced polymer (CFRP) and glass-fiber-reinforced polymer (GFRP) in bar and sheet forms. Various strengthening materials such as a CFRP, GFRP, and prestressing (PS) strand are applied to the NSM, EP, EB, and SE methods, followed by flexural experiments. In addition, changes in the ductility of the RC structures were examined. The concrete EP and near-surface mounting prestressing (NSM(P)) methods have a stiffness that is almost double the non-strengthened specimen. However, because the EP and EB methods are brittle, the NSM(P) method with ductile behavior is considered the most effective.

Objective To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. Background Resveratrol is considered an anti-inflammatory polyphenolic stilbene involved in the modulation of inflammation. Materials and methods Periodontitis was induced in mouse molars using a 5-day ligature model followed by the left second molar extraction and 50 µM resveratrol treatment for 1 and 2 weeks. We then examined specimens treated for 1 week histologically and with immunostaining. Microfocus-computed tomography (micro-CT) was used to examine the bone volume formation. Results After 1 week of treatment, proinflammatory cytokine levels (TNF-alpha and IL6), cells exhibiting neutrophil and macrophage marker (MPO), cell proliferation marker (Ki67), and preosteoblastic marker (RUNX2) reactivity decreased in the resveratrol-treated specimens compared to the control group. In contrast, we observed a higher number of CD31-, F4/80-, and osteocalcin- (OCN-) positive cells in the resveratrol-treated specimens. After 2 weeks, micro-CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol-treated group. Conclusion After 1 week, the resveratrol-treated specimens revealed evidence of inflammation modulation compared to the control group. These data suggest that resveratrol not only affects inflammation control but also is useful for treating periodontitis-related tissue defects and bone regeneration.

Graphene oxide (GO) was decorated with gold-aryl (Au-C) nanoparticles AuNPs-COOH by sodium borohydride reduction of aryldiazonium tetrachloroaurate(III) salt at room temperature in aqueous solutions. Brunauer-Emmett-Teller measurements supported GO anchoring by AuNPs modified with COOH; surface area dropped significantly. Morphology of AuNPs-COOH/GO nanocomposite (NC) was probed using AFM and TEM, showing NC’s surface roughness and wrinkling. XPS results suggest the clear reductive reaction of tetrachloroaurate anion into metallic gold in AuNPs-COOH/GO along with detailed interpretations of functional groups’ nature. Molecular dynamics calculations endowed support of favorable wrinkling at the edges and carboxyl intercalation to GO surface of types π- π, hydrogen bonding, and hydrophobic interactions. Solvent accessible surface area calculations of GO showed a decrease in total surface area. Environmental nanoremediation of the catalytic reduction of 4-nitrophenol, a priority pollutant listed by USEPA, was investigated. The apparent rate constants Kapp of four catalytic reduction cycles of nitrophenol were measured. The highest value is 1.17 × 10-1 min-1 for the first cycle which decreased to 4.49 × 10 -2 min -1 for the fourth cycle. The variations in rate constants were measured with different conditions, including NaBH 4 concentrations, NC loadings and NC incubating time in NaBH4.

A basic oxygen furnace (BOF) slag was used to stabilize lead (Pb) in a mine waste. Stabilization efficiencies differed depending on the slag contents (i.e., 3, 5, and 10 wt.%) and the water contents (i.e., 0.05–5.0 L/kg), varying from 52.2 to 98.0%, and both the slag contents and the water contents positively affected the stabilization efficiency. X-ray photoelectron spectroscopy suggested an evidence that precipitation and adsorption mechanisms were involved. When the contribution of each mechanism was determined, the increase in the BOF slag content mainly increased adsorption mechanism probably because of the increase in the adsorption sties. The increase in the water content, on the other hand, facilitated precipitation mechanism by lowering the ionic strength. Stabilized Pb could be mobilized at redox potential of 20–85 mV due to the reductive dissolution of Fe and Mn oxides. Sequential extraction results demonstrated that the adsorbed Pb became mobilized, and the fraction of exchangeable Pb increased.

This study examines how the high-fat diet (HFD) affects mitochondrial dynamics and biogenesis, and also whether combining it with low-intensity endurance exercise adds to these effects. Six 8-week-old male Sprague&ndash, Dawley (SD) rats were put on control (CON, standard chow diet), HF (HFD intake), and HFEx (HFD + low-intensity treadmill exercise) for 6 weeks. As a result, no change in body weight was observed among the groups. However, epididymal fat mass increased significantly in the two groups that had been given HFD. Blood free fatty acid (FFA) also increased significantly in the HF group. While HFD increased insulin resistance (IR), this was improved significantly in the HFEx group. HFD also significantly increased mitochondrial biogenesis-related factors (PPAR&delta, PGC-1&alpha, and mtTFA) and mitochondrial electron transport chain proteins, however, no additional effect from exercise was observed. Mitochondrial dynamic-related factors were also affected: Mfn2 increased significantly in the HFEx group, while Drp1 and Fis-1 increased significantly in both the HF and HFEx groups. The number of mitochondria in the subsarcolemmal region, and their size in the subsarcolemmal and intermyofibrillar regions, also increased significantly in the HFEx group. Taken overall, these results show that HFD in combination with low-intensity endurance exercise has no additive effect on mitochondrial biogenesis, although it does have such an effect on mitochondrial dynamics by improving IR.

High-salt intake and high-fructose intake are risk factors for hypertension via oxidative stress and inflammation. T helper (Th)17 lymphocytes play an important role in the development of hypertension. Here, we tested the hypothesis that activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in Dahl salt-sensitive (SS) but not Dahl salt-resistant (SR) rats. Eight-week-old male SS and SR rats were offered 20% fructose solution or tap water only for 4 weeks. Systolic blood pressure was measured by the tail-cuff method. T lymphocyte [Th17 and T regulatory (Treg)] profiling was determined via flow cytometry. The expression of Th17-related (IL-17A, IL-17RA, IL-23R and RORγt) and Treg-related (IL-10, CD25, FOXP3 and TGFβ) factors were measured via ELISA or qRT-PCR. Th17 lymphocytes isolated from high-fructose-fed SS rats were intraperitoneally injected into recipient SS and SR rats, and recombinant IL-23 protein was subcutaneously injected into SS and SR rats to induce hypertension. High-fructose intake induced hypertension via the activation of pathogenic Th17 lymphocytes in SS but not SR rats. Injection of activated Th17 lymphocytes isolated from fructose-fed SS rats induced hypertension via increase of serum IL-17A only in recipient SS rats. In addition, injection of IL-23 induced hypertension via activation of pathogenic Th17 lymphocytes only in SS rats. Thus, activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in SS but not SR rats. These results indicate that immunologic tolerance plays an important role in protection against hypertension in SR rats., Summary: Activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in salt-sensitive rats. Immune activation plays an important role in the development of hypertension, whereas immune tolerance is protective against hypertension.

The bioaccessibility of heavy metals in soil is closely related to their potential risk. Therefore, developing techniques for reducing it needs considerable attention. In this study, we aimed to co-precipitate soil As(V) through an in situ formation of Fe oxides, thereby reducing its bioaccessibility. Soil As(V) was co-precipitated by introducing 2% Fe-nitrate (w/w) and 30% water (v/w) into soil at pH ~7. Two different neutralizing agents (NaOH and CaO) were used to induce the precipitation of Fe oxides, and their effects on the speciation of As were investigated. In all the stabilized soils, the exchangeable As fraction decreased, and the fraction of As bound to amorphous Fe oxides increased by a factor of more than 1.4. In contrast, a marked decrease in bioaccessibility of As was achieved using NaOH (40% to 7%). X-ray absorption spectroscopy analysis demonstrated that highly bioaccessible forms of calcium iron arsenate (yukonite and arseniosiderite) could be generated in CaO-stabilized soil. Our study found that neutralizing agents may play an important role in stabilizing As(V) and lowering its bioaccessibility through determining the type of formed Fe oxides in soil.

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes accompanied by increased infiltration of immune cells. Previous studies have demonstrated that hispidulin (4',5,7-trihydroxy-6-methoxyflavone, HPD) has various pharmacological benefits such as anti-fungal, anti-inflammation, and anti-allergic effects. This study investigated the effectiveness of HPD to treat psoriasis using an imiquimod (IMQ)-induced mouse model and activated keratinocytes. IMQ was topically applied to the back skin of mice for six consecutive days, and the mice were orally administered HPD. Based on the histological observation and immunological analysis, oral administration of HPD suppressed psoriatic characteristics including skin thickness, psoriasis area severity index, transepidermal water loss, and neutrophil infiltration. HPD alleviated pathologically increased levels of immunoglobulin G2a, myeloperoxidase, and tumor necrosis factor-α. Splenic Th1 and Th17 cell populations were also reduced by HPD in the murine model. In addition, in activated keratinocytes, HPD inhibited gene expression of Th1- and Th17-associated cytokines and chemokines, and phosphorylation of mitogen-activated protein kinases and nuclear factor-κB. In summary, HPD alleviates psoriasis skin inflammation in vivo and in vitro. Therefore, we suggest that HPD would be a potent therapeutic candidate for the treatment of psoriasis.

The water and oxygen contents of the vadose zone change cyclically depending upon the meteorological condition (e.g., intermittent rainfall), which can affect the biogeochemical reactions that govern the fate of arsenic (As). To simulate and evaluate the transient behavior of As in this zone when subjected to repeated wet and dry conditions, soil column experiments with different soil properties were conducted. Three wetting–drying cycles resulted in the fluctuation of water and dissolved oxygen contents, and consequently, the reduction–oxidation potential in the soil columns. Under these circumstances, the biotic reduction of As(V) to As(III) was observed, especially in the column filled with soils enriched in organic matter. Most of the As was found to be associated with soil particles rather than to be dissolved in the pore water in all of the columns tested. Retention of As was more preferable in the soil column with a higher Fe content and bulk density, which provided more sorption sites and reaction time, respectively. However, a considerable amount of soil-bound As could be remobilized and released back to the pore water with the repetition of wetting and drying due to the transformation of As(V) to As(III).

Adiponectin exhibits potent antitumor activities. Herein, we examined the molecular mechanisms underlying suppression of tumor growth by globular adiponectin (gAcrp). We demonstrated that gAcrp suppressed B‐cell lymphoma 2 (Bcl‐2) expression, an anti‐apoptotic gene, by inducing its mRNA destabilization, which was accompanied with a decrease in cell viability and increased caspase‐3 activity in hepatic cancer cells. In addition, gAcrp increased expression of tristetraprolin (TTP) and AU‐rich element RNA‐binding protein 1 (AUF1), which are mRNA stability regulatory proteins. Moreover, gAcrp‐induced suppression of Bcl‐2 expression was abrogated by knockdown of TTP or AUF1. These data indicate that gAcrp induces apoptosis of hepatic cancer cells by TTP‐ and AUF1‐mediated Bcl‐2 mRNA destabilization, and further suggest that TTP and AUF1 are novel targets mediating the antitumor activity of adiponectin.

The purpose of this study is to compare and evaluate the radiation shielding efficiency of micro- and nanosized tungsten materials using powder type with 1-mm thick with respect to the X-ray exposure condition. We used an X-ray imaging system, and micro- and nanosized tungsten materials were manufactured and used. The exposure conditions were tube voltage of 41–140 kVp at fixed tube current of 10 mAs to evaluate radiation dose; we measured each transmissivity using an acrylic phantom. Also, a scanning electron microscope and X-ray diffraction spectroscopy were used for evaluation of quantitative microstructural analysis and the amount of crystalline material, respectively. The results of X-ray transmissivity measurements show that the nanosized tungsten shielding has much lower transmissivity than the microsized tungsten shielding from 41 to 100 kVp. At tube voltage of 100 kVp or more, there was almost no difference in the transmissivity of the two types of shielding. In conclusion, our results demonstrate that shielding effectiveness using nanosized tungsten material is better than that of microsized tungsten material at relatively low tube voltage of 41–100 kVp.

Arsenic stabilization mechanism in a mine waste was investigated using a basic oxygen furnace (BOF) slag. A lab-scale batch test was carried out to stabilize As in the mine waste samples for 1 h, where various amounts of the BOF slag and distilled water were introduced. Different stabilization efficiencies were observed depending on the stabilizing conditions (i.e., BOF slag content and water to mine waste (L/S) ratio). The stabilization efficiencies ranged 75–92% and 92–95% for 5% (w-slag/w-mine waste) and 10% BOF slag treated mine waste samples, respectively. Interestingly, a notable effect of the L/S ratio on the stabilization efficiency was observed (78% at 0.05 L/kg, and 23% at 1.0 L/kg) at the 3% BOF slag treatment. The point of zero charge and the stabilizing pH indicated that the BOF slag surface was negatively charged. Based on the comparison of fresh and Ca-reduced BOF slags, As stabilization mechanism was determined to be adsorption through cation bridges by Ca2+. The Surface analysis using X-ray photoelectron spectroscopy (XPS) and the stabilization experiment conducted at lower pH provided evidence that the hindrance of As adsorption resulted from Ca(OH)2 precipitation on the BOF slag surface when excess water (1.0 L/kg) was added. Such effect of water content seemed to be overcome by providing an excessive amount of the BOF slag. When an ample amount of Ca2+ is provided and pH is maintained around 11, not only As adsorption but also calcium arsenate precipitation occur, and both contributed to the stabilization mechanisms of As.

Since elevated osteoclast formation and/or activity by inhibitory responses against pathogens leads to diverse osteolytic bone diseases including periodontitis, inhibition of osteoclast differentiation and bone resorption has been a primary therapeutic strategy. In this study, we investigated the therapeutic potential of a novel benzamide-linked molecule, OCLI-070, for preventing alveolar bone loss in mice with ligature-induced experimental periodontitis. OCLI-070 inhibited osteoclast formation by acting on both early and late stages of differentiation, and attenuated the induction of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific genes. In addition, OCLI-070 significantly suppressed the formation of actin rings and resorption pits. Analysis of the inhibitory action of OCLI-070 showed that it markedly suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced extracellular signal-regulated kinase (ERK) and NF-κB signaling cascades. Moreover, OCLI-070 prevented ligature-induced alveolar bone erosion in mice by suppressing osteoclast formation. These findings demonstrate that OCLI-070 attenuated osteoclast differentiation and function as well as ligature-induced bone erosion by inhibiting RANKL-mediated ERK and NF-κB signaling pathways.

Staphylococcus aureus membrane vesicles (MVs) aggravate atopic dermatitis (AD) through the delivery of bacterial effector molecules to host cells and the stimulation of inflammatory responses. This study investigated the inhibitory effect of thymol, a phenolic monoterpene found in essential oils derived from plants, on the worsening of AD induced by S. aureus MVs both in vitro and in vivo. The sub-minimal inhibitory concentrations of thymol disrupted S. aureus MVs. Intact S. aureus MVs induced the expression of pro-inflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α) and chemokine (IL-8 and monocyte chemoattractant protein-1) genes in cultured keratinocytes, whereas thymol-treated S. aureus MVs did not stimulate the expression of these genes. Topical application of thymol-treated S. aureus MVs or treatment with thymol after intact S. aureus MVs to AD-like skin lesions diminished the pathology of AD. This included decreases in epidermal/dermal thickness and infiltration of eosinophils/mast cells, and inhibited expression of pro-inflammatory cytokine and chemokine genes in mouse AD model. Moreover, thymol significantly suppressed the Th1, Th2, and Th17-mediated inflammatory responses in AD-like skin lesions induced by S. aureus MVs, and reduced the serum levels of immunoglobulin (Ig) G2a, mite-specific IgE, and total IgE. In summary, thymol disrupts S. aureus MVs and suppresses inflammatory responses in AD-like skin lesions aggravated by S. aureus MVs. Our results suggest that thymol is a possible candidate for the management of AD aggravation induced by S. aureus colonization or infection in the lesions.

Inflammation is an important biological reaction in the body in response to external stimuli. Excessive inflammation causes various inflammatory disorders such as allergic hypersensitivity, autoimmune disease, rheumatoid arthritis, and cancer. Macrophages play a major role in the inflammatory response by producing inflammatory mediators such as nitric oxide, prostaglandin E2, and pro-inflammatory cytokines. Natural products are often a source of bioactive compounds, which have great potential as novel therapeutic agents. Amomum xanthoides extract has been shown to possess various pharmacological activities including anti-inflammatory activity. This study evaluated the anti-inflammatory potential of o-vanillic acid (o-VA), a major compound in A. xanthoides, using lipopolysaccharide (LPS)-induced macrophages and in vivo animal models. o-VA decreased, in a concentration-dependent manner, the LPS-induced gene expression and production of inflammatory mediators, such as inducible nitric oxidase/cyclooxygenase-2 and pro-inflammatory cytokines, by reducing the nuclear factor-B activation. In addition, o-VA dose-dependently ameliorated acetic acid-induced vascular permeability and zymosan-induced leukocyte migration. Thus, we suggest that o-VA can be used as a pharmacological agent or food supplement in the treatment of inflammatory conditions.

Mast cells play a major role in allergic inflammation by the release of histamine, an important mediator of type I hypersensitivity. Cencerns regarding potential harmful effects of perfluorooctane sulfonate (PFOS) have been raised. Previous studies reported that PFOS causes various adverse effects such as immunotoxicity and neurotoxicity. This report studied whether PFOS affects mast cells-mediated allergic inflammation. Ovalbumin-induced active systemic anaphylaxis model was used to assess for the type I hypersensitivity. After sensitization, mice were orally administered with PFOS and then allergic symptoms such as hypothermia and increase of serum allergic mediator were measured. In additional, this study investigated whether PFOS deteriorate allergic inflammation in immunoglobulin E-stimulated mast cells. PFOS aggravated the allergic symptoms such as hypothermia, and increase of serum histamine, tumor necrosis factor-α and immunoglobulin (Ig) E/ G1. PFOS increased the release of histamine and β-hexosaminidase through the up-regulation of intracellular calcium in IgE-stimulated mast cells. PFOS also enhanced the gene expression of pro-inflammatory cytokines by activating nuclear factor-κB. This study demonstrated that PFOS more intensifies the mast cell-mediated allergic inflammation.

Recent advances in endoscopic technology allow clinicians to not only detect digestive diseases early, but also provide appropriate treatment. The development of various therapeutic endoscopic technologies has changed the paradigm in the treatment of gastrointestinal diseases, contributing greatly to improving the quality of life of patients. The application of robotics for gastrointestinal endoscopy improves the maneuverability and therapeutic ability of gastrointestinal endoscopists, but there are still technical limitations. With the development of minimally invasive endoscopic treatment, clinicians need more sophisticated and precise endoscopic instruments. Novel robotic systems are being developed for application in various clinical fields, to ultimately develop into minimally invasive robotic surgery to lower the risk to patients. Robots for endoscopic submucosal dissection, autonomous locomotive robotic colonoscopes, and robotic capsule endoscopes are currently being developed. In this review, the most recently developed innovative endoscopic robots were evaluated according to their operating mechanisms and purpose of use. Robotic endoscopy is an innovative treatment platform for future digestive endoscopy.

Biodiesel is an environmentally friendly, biodegradable, and renewable source of energy. It can be used as an alternate source of energy to reduce overburden on fossil-based fuels. The use of waste cooking oil (WCO) for biodiesel production may solve its management problem and provide additional revenue. Rhodococcus is an oleaginous microbe that can utilize various feedstock as a carbon source for growth and lipid production. In this study, WCO was used as a carbon source and the effect of various surfactants on growth and lipids accumulation was studied. Production media components optimized using response surface design and cultivation in optimized media i.e., WCO (1.15%): NH4Cl (0.09%): NaCl (0.97%): PEG (0.05%) resulted in 3.42 ± 0.06 g CDW/L biomass production, 2.39 ± 0.04 g/L lipid production with 70 ± 4.0% w/w lipid accumulation. Produced lipids were analyzed for fatty acid methyl esters (FAMEs) composition and composed of palmitoleic acid (16:1, 61.68%) > palmitic acid (C16:0, 21.48%) > myristic acid (C14:0, 12.95%) > stearic acid (C18:0, 2.35%) > pentadecanoic acid (C15:0, 0.74%) > heptadecanoic acid (C17:0, 0.72%) > oleic acid (C18:1, 0.05%). Properties of biodiesel depend on FAMEs composition and analyzed as cetane number (CN, 56.5), iodine value (IV, 63.7), cold filter plugging point (CFPP, −9.6), cloud point (CP, 6.3 °C), pour point (PP, 0.028 °C), oxidation stability (OS, infinity), high heating value (HHV, 38.9), kinematic viscosity (υ, 3.2 mm2/s), and density (ρ, 0.87 g/cm3). The properties of produced biodiesel satisfy the international standards EN14214 and IS15607 and suggest that biodiesel produced from WCO oil can be used as an energy source.

Background Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FceRI-mediated mast cell activation and allergic inflammation. Methods In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model. Results We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FceRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner. Conclusions Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FceRI-mediated mast cell activation.

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.