Kim, Jihyun;Kim, Jaehoon;Huang, Zhouchi;Goo, Nayeon;Bae, Ho Jung;Jeong, Yongwoo;Park, Ho Jae;Cai, Mudan;Cho, Kyungnam;Jung, Seo Yun;Bae, Soo Kyung;Ryu, Jong Hoon
Biomolecules & Therapeutics
/
v.27
no.3
/
pp.327-335
/
2019
As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.
A total of 36 carbon steel and stainless steel bolted connections subjected to shear loading at different strain rates was experimentally investigated. The connection specimens were fabricated from carbon steel grades 1.20 mm G500 and 1.90 mm G450, as well as cold-formed stainless steel types EN 1.4301 and EN 1.4162 with nominal thickness 1.50 mm. The connection tests were conducted by displacement control test method. The strain rates of 10 mm/min and 20 mm/min were used. Structural behaviour of the connection specimens tested at different strain rates was investigated in terms of ultimate load, elongation corresponding to ultimate load and failure mode. Generally, it is shown that the higher strain rate on the bolted connection specimens, the higher ultimate load was obtained. The ultimate loads were averagely 2-6% higher, while the corresponding elongations were averagely 8-9% higher for the test results obtained from the strain rate of 20 mm/min compared with those obtained from the lower strain rates (1.0 mm/min for carbon steel and 1.5 mm/min for stainless steel). The connection specimens were generally failed in plate bearing of the carbon steel and stainless steel. It is shown that increasing the strain rate up to 20 mm/min generally has no effect on the bearing failure mode of the carbon steel and stainless steel bolted connections. The test strengths and failure modes were compared with the results predicted by the bolted connection design rules in international design specifications, including the Australian/New Zealand Standard (AS/NZS4600 2018), Eurocode 3 - Part 1.3 (EC3-1.3 2006) and North American Specification (AISI S100 2016) for cold-formed carbon steel structures as well as the American Specification (ASCE 2002), AS/NZS4673 (2001) and Eurocode 3 - Part 1.4 (EC3-1.4 2015) for stainless steel structures. It is shown that the AS/NZS4600 (2018), EC3-1.3 (2006) and AISI S100 (2016) generally provide conservative predictions for the carbon steel bolted connections. Both the ASCE (2002) and the EC3-1.4 (2015) provide conservative predictions for the stainless steel bolted connections. The EC3-1.3 (2006) generally provided more accurate predictions of failure mode for carbon steel bolted connections than the AS/NZS4600 (2018) and the AISI S100 (2016). The failure modes of stainless steel bolted connections predicted by the EC3-1.4 (2015) are more consistent with the test results compared with those predicted by the ASCE (2002).
Journal of Elementary Mathematics Education in Korea
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v.22
no.3
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pp.309-330
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2018
The purpose of this study is to identify possibility of a mathematical problem posing ability by presenting problem posing tasks with different degrees of structure according to the study of Stoyanova and Ellerton(1996). Also, the results of this study suggest the direction of gifted elementary mathematics education to increase mathematical creativity. The research results showed that mathematical problem posing ability is likely to be a factor in identification of gifted students, and suggested directions for problem posing activities in education for mathematically gifted by investigating the characteristics of original problems. Although there are many criteria that distinguish between gifted and ordinary students, it is most desirable to utilize the measurement of fluency through the well-structured problem posing tasks in terms of efficiency, which is consistent with the findings of Jo Seokhee et al. (2007). It is possible to obtain fairly good reliability and validity in the measurement of fluency. On the other hand, the fact that the problem with depth of solving steps of 3 or more is likely to be a unique problem suggests that students should be encouraged to create multi-steps problems when teaching creative problem posing activities for the gifted. This implies that using multi-steps problems is an alternative method to identify gifted elementary students.
Objective: Mulberry (Morus alba L.) is a cultivated shrub grown widely in the sub-tropical and tropical areas. It has been shown that mulberry leaf contains high levels of protein while having polyphenols as phytonutrients. Therefore, it is important to conduct an experiment to assess potential toxic level from mulberry on behavior, blood hematological and coagulation parameter using Sprague-Dawley (SD) rats. Methods: Both male and female SD rats were given an intragastric administration of respective treatments of mulberry leaf intakes (control, low and high levels). Parameters of feed intake, hematological and coagulation of blood parameters, as well as liveweight changes were taken during the 7 d of adaptation, 28 d of treatment exposure, and 14 d of recovery periods, respectively. All treatment data were statistically analyzed using analysis of variance of SPSS17.0 for Windows Statistical Software following the Randomized complete block design with sex as a block. Results: Most of the parameters of the physical symptoms of the SD rats, were not significantly different (p>0.05) when compared with that of the control group. Those which remain unchanged in each dose group were, body weight (BW) gain, feed intake, the hematology and coagulation indexes. Although, there were a few individual indicators that were abnormal, but the overall physiological appearance of the rats were normal. Conclusion: Results under this experiment revealed that most hematological and coagulation parameters of the SD rats in both male and female were normal, although the weight gain of female rats in high-dose group was significantly reduced than those of the male rats. Under this study, the use of mulberry leaf up to 2 g/kg BW did not result in abnormal phenomenon in the SD rats. These findings would offer useful information for further in vivo feeding trials in animals to extensively use of mulberry leaf to improve animal production, particularly in P.R. China.
Objective: The study was conducted to evaluate the effects of night light regimen on growth performance, antioxidant status and health of Lingnan Yellow broiler chickens from 1 to 21 days of age. Methods: A completely randomized factorial design involved 2 photoperiods (constant lighting [CL], 24 L:0 D and intermittent lighting [INL], 17 L:3 D:1 L:3 D)${\times}2$ light intensities (10 lx and 30 lx). A total of one thousand six hundred and eighty 1-d-old Lingnan Yellow broiler chicks were randomly divided into 4 treatments with 6 replicates (70 birds per replicate). The experiment lasted for 21 d. Results: Photoperiods and light intensities had no effect on average daily gain, feed conversion ratio, and mortality of the broiler chickens (p>0.05). The INL had a significant effect on average daily feed intake (p<0.05) of broiler chickens compared with CL. Photoperiod and light intensity had an interactive effect on melatonin (MT) concentration (p<0.05). At CL, reducing light intensity increased MT concentration; INL birds had higher MT but MT concentration was not affected by light intensity. There was an interactive effect on glutathione peroxidase (GPx) and catalase (CAT) in serum and total antioxidant capability (T-AOC) in liver between photoperiod and light intensity. With the decrease of light intensity, the activities of GPx and CAT in serum and T-AOC in liver increased in CL group (p<0.05). Broiler chickens reared under INL had better antioxidant status and 10 lx treatments had higher activities of CAT in serum than 30 lx (p<0.05). Different photoperiods and light intensities had no effect on malondialdehyde. There was an interaction between photoperiod and light intensity on serum creatine kinase (CK) concentration (p<0.05). At CL, the elevated light intensity resulted in an increase in CK content; INL birds had lower CK concentration especially in low light intensity group. Besides, INL and low light intensity significantly reduced the concentration of serum corticosterone and heat shock protein 70 (p<0.05). Serum immunoglobulin M contents were increased in broiler chickens reared under the INL compared with CL group (p<0.05). Conclusion: Results above suggest that the night light regimen of INL and 10 lx could be beneficial to the broiler chickens from 1 to 21 days of age due to the better health status and electricity savings.
Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.
In Lead-based reactor (LBR) severe accident, the meltdown and migration inside the reactor core will lead to fuel fragment concentration, which may further cause re-criticality and even core disintegration. Accurately predicting the migration and solidification behavior of melt in LBR severe accidents is of prime importance for safety analysis of LBR. In this study, the Moving Particle Semi-implicit (MPS) method is validated and used to simulate the migration and solidification behavior. Two main surface tension models are validated and compared. Meanwhile, the MPS method is validated by the L-plate solidification test. Based on the improved MPS method, the migration and solidification behavior of melt in LBR severe accident was studied furthermore. In the Pb-Bi coolant, the melt flows upward due to density difference. The migration and solidification behavior are greatly affected by the surface tension and viscous resistance varying with enthalpy. The whole movement process can be divided into three stages depending on the change in velocity. The heat transfer of core melt is determined jointly by two heat transfer modes: flow heat transfer and solid conductivity. Generally, the research results indicate that the MPS method has unique advantage in studying the migration and solidification behavior in LBR severe accident.
Objective: Choline deficiency, one main trigger for nonalcoholic fatty liver disease (NAFLD), is closely related to lipid metabolism disorder. Previous study in a choline-deficient model has largely focused on gene expression rather than gene structure, especially sparse are studies regarding to alternative splicing (AS). In modern life science research, primary hepatocytes culture technology facilitates such studies, which can accurately imitate liver activity in vitro and show unique superiority. Whereas limitations to traditional hepatocytes culture technology exist in terms of efficiency and operability. This study pursued an optimization culture method for duck primary hepatocytes to explore AS in choline-deficient model. Methods: We performed an optimization culture method for duck primary hepatocytes with multi-step digestion procedure from Pekin duck embryos. Subsequently a NAFLD model was constructed with choline-free medium. RNA-seq and further analysis by rMATS were performed to identify AS events alterations in choline-deficency duck primary hepatocytes. Results: The results showed E13 (embryonic day 13) to E15 is suitable to obtain hepatocytes, and the viability reached over 95% by trypan blue exclusion assay. Primary hepatocyte retained their biological function as well identified by Periodic Acid-Schiff staining method and Glucose-6-phosphate dehydrogenase activity assay, respectively. Meanwhile, genes of alb and afp and specific protein of albumin were detected to verify cultured hepatocytes. Immunofluorescence was used to evaluate purity of hepatocytes, presenting up to 90%. On this base, choline-deficient model was constructed and displayed significantly increase of intracellular triglyceride and cholesterol as reported previously. Intriguingly, our data suggested that AS events in choline-deficient model were implicated in pivotal biological processes as an aberrant transcriptional regulator, of which 16 genes were involved in lipid metabolism and highly enriched in glycerophospholipid metabolism. Conclusion: An effective and rapid protocol for obtaining duck primary hepatocytes was established, by which our findings manifested choline deficiency could induce the accumulation of lipid and result in aberrant AS events in hepatocytes, providing a novel insight into various AS in the metabolism role of choline.
Casein-derived antioxidant peptides by using microbial proteases have gained increasing attention. Combination of two microbial proteases, Protin SD-NY10 and Protease A "Amano" 2SD, was employed to hydrolyze casein to obtain potential antioxidant peptides that were identified by LC-MS/MS, chemically synthesized and characterized in a oxidatively damaged HepG2 cell model. Four peptides, YQLD, FSDIPNPIGSEN, FSDIPNPIGSE, YFYP were found to possess high 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability. Evaluation with HepG2 cells showed that the 4 peptides at low concentrations (< 1.0 mg/ml) protected the cells against oxidative damage. The 4 peptides exhibited different levels of antioxidant activity by stimulating mRNA and protein expression of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as nuclear factor erythroid-2-related factor 2 (Nrf2), but decreasing the mRNA expression of Kelch-like ECH-associated protein 1 (Keap1). Furthermore, these peptides decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), but increased glutathione (GSH) production in HepG2 cells. Therefore, the 4 casein-derived peptides obtained by using microbial proteases exhibited different antioxidant activity by activating the Keap1-Nrf2 signaling pathway, and they could serve as potential antioxidant agents in functional foods or pharmaceutic preparation.
Teoh, Ryan Liang Wei;Fong, Pei Yuan;Cai, Elijah Zhengyang;Yap, Yan Lin;Hing, Eileen Chor Hoong;Lee, Han Jing;Nallathamby, Vigneswaran;Ong, Wei Chen;Lim, Jane;Sundar, Gangadhara;Lim, Thiam Chye
Archives of Plastic Surgery
/
v.49
no.2
/
pp.195-199
/
2022
Nasolacrimal duct (NLD) damage is associated in the majority of type II and III naso-orbito-ethmoid (NOE) fractures. Our study aims to investigate the efficacy and safety of prophylactic NLD intubation in the setting of facial fractures, by comparing incidence of postoperative epiphora and wound infection. A retrospective matched control study was conducted on all patients with surgically treated facial fractures from 2008 to 2013 (n=280) (IRB ref number: DSRB 2013/01198). Patients with the following fracture types were included: NOE (n=16), frontal sinus (n=2), Le Fort II/III (n=8), and > 1 type (n=48). All patients in this study were included with the intention to treat. The study group comprised patients who were intubated, while the control group patients were not intubated. Each group had 37 patients matched for age, gender, fracture type, and injury type. A single oculoplastic surgeon skilled in lacrimal surgery performed the procedure for all intubated patients. Patients with more severe and complex facial fractures were intubated with bicanalicular Crawford stents. Postoperative epiphora and infective complications (both facial wound and dacryocystitis) were assessed at 1, 3, 6, and 12 months. There was no significant difference in incidence of either postoperative epiphora (p=0.152) or wound infection (p=0.556) comparing both groups. Reduced incidence of postoperative epiphora in the study group is statistically not significant and does not support the need for prophylactic intubation. If radiographic evidence of NLD disruption or regurgitation seen on syringing on the NLD intraoperatively is present, intubation is safe and efficacious only if performed by an expert.
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