In this study, the acute toxicity of Dendropanax morbiferus H.Lév leaf hot-water extracts (DMWE) was examined in male and female ICR mice. Mice were orally administered the DMWE at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no significant differences in change of BW between control and all DMWE treated-groups. In hematological and blood biochemical analysis, none of the parameters were affected by the DMWE. Similarly, there were no significant effects on markers for liver and kidney functions in all DMWE treated-groups. Since there were no adverse effects of the DMWE in single oral toxicity tests, even at the highest doses, it was concluded that the lethal dose 50 (LD50) of DMWE is estimated at > 2,000 mg/kg BW.

Subunit vaccines are being developed as a potential therapy for preventing microbial pathogen infection. In this study, the immunogenicity of recombinant Brucella (B.) abortus Fe/Mn superoxide dismutase (rFe/Mn SOD) protein as a subunit vaccine against B. abortus was investigated in BALB/c mice model. Brucella Fe/Mn SOD gene was cloned into a pcold-TF DNA vector. The bacterial recombinant protein was expressed using the Escherichia coli DH5α strain with a size of 82.50 kDa. The western blotting assay showed that rFe/Mn SOD reacted with Brucella-positive serum, indicating the potential immunoreactivity of this recombinant protein. After the second and third vaccinations, the peripheral CD4+ T cell population was increased significantly in the rFe/Mn SOD-immunized mice group compared to the PBS control group. Moreover, immunization of this recombinant protein increased the CD4+ T cell population from the first vaccination to the third vaccination. Meanwhile, the CD8+ T cells were slightly enhanced after the second vaccination compared to the first vaccination and compared to control groups. Fourteen days after the bacterial infection, the splenomegaly and the number of bacteria in the spleen were evaluated. The result showed that both rFe/Mn SOD and positive control RB51 decreased the bacterial replication in the spleen and the splenomegaly compared to control groups. Altogether, these results suggested that rFe/Mn SOD could induce host immunity against B. abortus infection.

This study evaluated the effect of a combination of acetaminophen (AAP), vitamin C (VC) and thioctic acid (TA) on reducing serum cortisol concentrations in mice with foot-and-mouth disease (FMD) vaccination. For 5 days from 3 days before FMD vaccination to 2 days after vaccination, mice were orally administered with AAP 600 mg/kg feed (n=25, AAPT), combination of AAP 600 mg and VC 200 mg per kg feed (n=25, AVCT) and combination of AAP 600 mg, VC 200 mg and TA 20 mg per kg feed (n=25, AVTT), respectively. From day 1 to day 7 after FMD vaccination, the cortisol concentration of all groups treated with the drug was significantly decreased compared to that of the positive control group with FMD vaccination (p<0.05). In conclusion, the combined treatment of AAP, VC and TA was the most effective in relieving stress from FMD vaccination compared to the single treatment.

Chlorine dioxide (ClO2) has recently emerged as an ideal disinfectant and has shown a wide range of antimicrobial activities in various pathogenic microorganisms. In this study, the virucidal effect of ClO2 at low concentration (0.02 ppm) and higher concentration (0.06 – 0.09 ppm) against Adenovirus and Herpesvirus was evaluated based on the NF T 72-281 and ASTM 1053-11 standard methods at different exposure times. The virus suspension was dried onto the carrier and then exposed to gaseous ClO2 (gClO2) at 22 ± 2∘C. For Adenovirus, exposure at a low concentration of ClO2 at the middle height resulted in the average log10 reduction of 0.95, 2.65, and 5.30 after 1, 3, and 6 h post-exposure (pe), respectively. Moreover, more than 4-log10 reduction was achieved at 4 and 6 h pe with higher concentrations of ClO2. On the other hand, the antiviral activity of gClO2 at the middle height was also effective against Herpesvirus. In particular, at 1 h pe, a less than 4-log10 reduction was observed at all examined concentrations of ClO2, whereas exposure for 3 and 6 h (with low concentration) or 2 h (with higher concentration) inactivated completely viruses attached to the carrier. These results suggested that ClO2 fumigation is a potential alternative method for disinfecting healthcare facilities, high-containment laboratories, and households with a safe concentration for human health.

Percutaneous balloon dilation with or without placement of an external biliary drain is a nonoperative alternative method for treating benign bilioenteric anastomotic strictures. Although this procedure has a high technical success rate, outcomes are less optimal when attempting to dilate refractory tight strictures. For the stricture, cutting balloon can be an option. We present four patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation. To the patients, a peripheral cutting balloon over-the-wire system was inflated, following subsequent conventional non-compliant balloon dilation. After the balloon dilation treatment, an external drainage catheter was placed through the stricture site and maintained for up to 30 days. Technical and end-treatment success was achieved in all four patients. In conclusion, the use of cutting balloon dilation may appear to be a safe and effective alternative method of treatment in patients with benign bilioenteric anastomotic strictures refractory to conventional balloon dilation.

This study investigated changes of milk production in dairy cows intramuscularly injected with drugs containing dexamethasone (DXM). Three types of dexamethasone formulations (Bueunde® (DXM 0.5 mg/mL), Dexason INJ.® (DXM 1 mg/mL) and Dexolone-20 inj.® (DXM 1 mg/mL)) were intramuscularly injected into sixteen healthy dairy cows each. Bueunde® was intramuscularly injected into 8 dairy cows with 5 mg (BED-1) and 10 mg (BED-2) of DXM once a day for 3 consecutive days, respectively. Dexason INJ.® was intramuscularly administered once into dairy cows with 20 mg (DXS-1, n=8) and 40 mg (DXS-2, n=8) of DXM, respectively. Dexolone-20 inj.® was intramuscularly injected once into dairy cows with 20 mg (DXS-1, n=8) and 40 mg (DXS-2, n=8) of DXM, respectively. Milk production (MP) of BED-1 and BED-2 significantly decreased during the drug administration and up to 48-hour post-drug treatment. Compared with the MP before drug administration, the MP of DXS-1 and DXL-1 was meaningfully decreased by 36 and 24-hour post-drug administration, respectively, and that in both DXS-2 and DXL-2 significantly decreased until 48-hour post-drug treatment. In conclusion, it was confirmed that the MP temporarily decreased by 48 hours after administration of DXM to dairy cows.

Based on many previous studies, this study reviewed the effects of needle-free intradermal injection (NFI) on the prevention of the incidence of lesions at the injection site in pork from pigs vaccinated with the foot-and-mouth disease vaccine, the reduction of the vaccine dose, the stress-relief of vaccination, and the reduction of farm worker-related injuries. The vaccine and drugs injected with the NFI pass through the tissue and are widely dispersed along the path of least resistance, resulting in a vastly dispersed, spider-web-like distribution of the medication and absorbed quickly. In addition, since NFI is inoculated into the dermal layer where immune cells are abundantly distributed, even a small amount of vaccination shows an antibody-forming effect similar to that of the conventional needle intramuscular injection. NFI is a method suitable for animal welfare because the vaccine or drug is widely dispersed over the inoculation site and causes less pain or stress than the needle intramuscular injection. Use of NFI system for the vaccination and drug delivery improves work efficiency in farms and reduces the incidence of musculoskeletal disorders in farm workers. In the future, it is judged that in-depth studies are needed on the effect of improving productivity and reducing the dose of antibiotics through NFI.

This study investigated chlorpheniramine maleate (CPM) residues in milk of intramuscularly dosed dairy cows and established the withdrawal time (WT) of CPM in milk. Sixteen healthy Holstein cows were injected with 10 (CPM-1) and 20 mL (CPM-2) of the drug containing 4 mg/mL of CPM, respectively. After administration of CPM, milk samples were collected from all cows at 12 hour intervals for 5 days. CPM residue concentrations in milk were determined using LC-MS/MS. The correlation coefficient of the calibration curve was 0.9956, and the limits of detection and quantification (LOQ) were 0.6 and 1.0 μg/kg, respectively. Recoveries ranged between 98.5-115.0%, and coefficient of variations were less than 10.96%. After treatment, CPM in CPM-1 and CPM-2 was detected below the LOQ in all milk samples at 12 hours. According to the European Medicines Agency’s guideline on determination of withdrawal periods for milk, withdrawal periods of both CPM-1 and CPM-2 in milk were established to 12 hours. In conclusion, the developed analytical method is sensitive and reliable for detection of CPM in milk, and the estimated WT of CPM in bovine milk will contribute to ensuring the safety of milk.

It has been discovered that the isosaccharinic acid (ISA) formed in a cellulose degradation leachate were capable of forming soluble complexes with thorium, uranium (IV) and plutonium. Since 1993, the ISA has received particular attention in the literature due to its ability to complex a range of radionuclides, potentially affecting the migration of radionuclides. ISA is formed as a result of interactions between cellulosic materials within the waste inventory and the alkalinity resulting from the use of cementitious materials in the construction of the repository. In an alkaline cementitious environment, cellulose degrades mainly via a peeling-off reaction. The main degradation product is ISA, a polyhydroxy type of ligand forming stable complexes with tri- and tetravalent radionuclides. ISA can have an adverse effect on the sorption of radionuclides to an extent which depends on its concentration in the cement pore water and potentially enhance their mobility. The concentration of ISA is governed by several factors such as cellulose loading, cement porosity, extent of cellulose degradation, etc. The sorption of ISA on cement, however, is the process which governs the concentration of ISA in the pore water. According to the experimental result from a literature, the ISA concentration in facilities with a cellulose loading of 5% is calculated to be of the order of 10−4 M. At this level, the effect of cellulose degradation products on radionuclide sorption is negligibly small. Recently in Korea, cellulous limits as waste acceptance criteria is studying and planning to prepare the detailed requirement for near surface radioactive waste disposal facilities. It is desirable to suggest consideration on cellulose disposal limits around the time that the regulatory body and concern organizations establish the cellulose disposal limits as follows. Firstly, identify the cellulose effect on the sorption of the nuclides as cementitious disposal environments such as affected nuclides, threshold value and contribution to radiological risks under domestic disposal environment. Secondly, make sure and consider the difference between lab-scale experimental conditions and probability occurring in real disposal conditions such as probability for generation and persistence of pH in cellulosic material disposal conditions and cellulosic material disposal methods. Finally, consider characterization of cellulosic material such as polymerization, contents of cellulose in law material and time of degradation process. As a result, desirable cellulose limits are to set up for both safety and economic aspect.

Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays. Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

The present study is designed to investigate the antibacterial effect of the hot-water and various ethanol extracts from the leaves of Dendropanax morbifera L. (DML) against Porphyromonas gingivalis (P. gingivalsis). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 30, 50 and 70% ethanol extract of DML against P. gingivalis decreased in a concentration-dependent manner. However, MIC and MBC of hot-water and 30% ethanol extract against P. gingivalis were the same as 3.13 and 6.25 mg/mL, respectively. In the bacterial growth inhibition test, the growth of P. gingivalis in the group treated with MBC and 2×MBC of DML hot-water extract was statistically significantly decreased from 6 h after incubation compared to the control group (p<0.001). From the results portrayed above, aqueous extract from DML at the concentration of 6.25 mg/mL can be usefully used to suppress infection of P. gingivalis, a major causative agent of periodontal disease.

We investigated the effect of a synthetic complement peptide C3a on the outcome of Brucella abortus 544 infection in a murine macrophage cell line RAW264.7 cell. First, we determined the highest non-cytotoxic concentration of the peptide in the cell line. We also found that the peptide significantly increased the growth of the bacteria at 8 and 24 h. Although the number of bacterial CFU was also elevated at 48 and 72 h, the increases were not significant as compared to controls. We further investigated the effect of C3a peptide on the growth of Brucella by pre-incubating the peptide at various temperatures and found that the effect was reversed at 24 h post-incubation suggesting that incubation of peptide at high temperatures including 65°C or 95°C could inactivate its action. This also could indicate the beneficial effect of high temperature during infection. Although several studies reported the inhibitory effect of different antimicrobial peptides including C3a, the present study preliminarily revealed that it had no positive contribution on the control of B. abortus 544 infection in vitro and indirectly to its receptor, CD88, which belongs to GPCR. Moreover, the encouraged further exploration of the effect of other similar peptides would be performed for the purpose of finding Brucella-host cell interaction for the control of disease progression.

This study compared the immune responses, stress relief and weight gains of needle or needle-free intramuscular and needle-free intradermal vaccination in pigs. When the same amount of a foot-and-mouth disease (FMD) vaccine was administered to pigs, antibody titers at 4 weeks after the 1st and 2nd FMD vaccination were not significantly different between the needle (IM-S) and needle-free (NM-P250) intramuscularly vaccinated groups, but the weight gain of NM-P250 was significantly increased compared to that of IM-S at 8 weeks after the 2nd FMD vaccination (p<0.05). In addition, serum cortisol concentrations of NM-P250 were considerably decreased compared to those of IM-S on the 5th and 7th day after the 1st and 2nd FMD vaccination (p<0.05). However, the antibody titers of IM-S vaccinated with 2 mL of FMD vaccine were significantly increased compared to those of the needle-free intradermal vaccinated group with 0.5 mL of FMD vaccine at 4 weeks after the 1st and 2nd FMD vaccination (p<0.05). In conclusion, the needle-free intramuscular injection for the FMD vaccination can be chosen for weight gain and stress relief in pigs.

This study aims to investigate the effects of exogenous succinic acid (SCA) on Brucella (B.) abortus infection in macrophage RAW 264.7 cells and ICR mice. Firstly, the in vitro experiment was conducted by MTT cytotoxicity and bacterial internalization assay to evaluate the uptake of B. abortus into macrophage cells. Two non-cytotoxic concentrations of SCA demonstrated attenuated invasion of Brucella into macrophages at 30 and 45 min post- infection (pi). Secondly, ICR mice were treated with SCA and infected with B. abortus. On day-14 pi, spleen and blood serum were collected to evaluate the bacterial burden and total spleen weight as well as the production of cytokine/chemokine, respectively. The results showed that SCA treatment promoted bacterial growth and reduced the total spleen weight in mice. Furthermore, SCA treatment increased the level of IL-10 cytokine in the sera, while dampening the production of MCP-1 chemokine compared to the control. The results of bacterial load in spleen and spleen weight together with cytokine/chemokine production profile in the sera indicated that SCA induced the host anti-inflammatory response which is beneficial for the survival of Brucella. Therefore, these findings suggest that SCA contributed to host immunity against Brucella infection and the emerging potential topic-immunometabolism should be invested for further investigations.

종래의 게임에서, 널리 사용되고 있는 난수는 게임 서비스 제공자에 의하여 일방적으로 제공되기 때문에, 게 임 이용자가 제공받은 난수가 어떠한 개입이나 조작이 있었는지를 검증하는 것은 어렵다. 본 논문은 상호 참 여형 난수 발생기인 TogetheRand를 제안한다. 제안된 방법은 이더리움 블록체인 시스템 위에서 작동되는 스 마트 컨트랙트이다. 제안된 방법의 난수성을 Dieharder tests를 이용하여 테스트하였다. 제안된 방법은 많은 사람들이 난수 생성에 참여할 수 있고, 모든 입력값을 확인할 수 있으며, 블록체인 시스템으로 인하여 정상 작동 여부가 보장되기 때문에 게임 이용자와 제공자 모두가 신뢰할 수 있는 방법이다. 제안된 방법은 게임 등의 신뢰성 있는 난수가 필요한 응용 분야에서 두루 적용될 수 있을 것이다. 본 논문에서 사용된 코드는 ht tps://github.com/TyeolRik/TogetheRand 에 공개되어 있다.

Nypa fruticans Wurmb (NFW) contains a large amount of phenolic acid and flavonoids, and is popular as a superfood in Myanmar. NFW has various biological activities, such as anti-inflammatory, anti-oxidant, and neuroprotective properties; however, the anti-cancer effect of NFW have not been reported. In this study, we investigated the anticancer activity of water extracts of NFW (WeNFW) and the underlying mechanism in human FaDu hypopharyngeal squamous carcinoma cells. The WeNFW inhibited FaDu cell growth in a dose-dependent manner without affecting normal cells (L929), as determined by an MTT assay and Live and Dead assay. In addition, the concentrations of WeNFW without cytotoxicity (0.025, 0.05, and 0.1 mg/mL) inhibited wound healing and colony formation. Furthermore, WeNFW significantly induced apoptosis through the proteolytic cleavage of caspase-3 and -9, poly (ADP-ribose) polymerase, and downregulation of Bcl-2 and upregulation of Bax in FaDu cells, as determined by DAPI staining, FACS analysis, and western blot analysis. Taken together, these results suggest that WeNFW exhibits potent anti-cancer effects by suppressing the growth of oral cancer cells, wound healing and colony formation activity. Via mitrochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, WeNFW can provide a natural chemotherapeutic drug for oral cancer in humans.