• Research in Vestibular Science
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• v.17 no.4
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• pp.142-151
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• 2018

Objectives: Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. Methods: Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. Results: Two or 3 types of unit could be classified according to the morphology of spikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. Conclusions: Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• Journal of Microbiology and Biotechnology
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• v.28 no.12
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• pp.2079-2094
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• 2018

Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

• The Korean Journal of Oral and Maxillofacial Pathology
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• v.42 no.6
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• pp.189-198
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• 2018

A 31 years old female had been suffered from a bony swelling in right premolar region of the mandible for 12 years, recently grown rapidly. A fistula tract developed on the right anterior mandibular border, but the lesion was relatively asymptomatic. In the radiological examination, the tumor mass was irregularly mixed with radiolucent and radiopaque areas, forming multiple cystic spaces. Under the diagnosis of calcifying odontogenic cyst, the mandibular mass was resected and examined pathologically. After decalcification, the dissected tumor mass showed multiple small cystic spaces and calcifying fibrous tissue, mimicking calcifying odontogenic cyst or ameloblastoma. Histological observation showed many calcifying cementoid materials and ossifying trabeculae. The cystic spaces were turned out to be dilated vascular channels lined by endothelial cells, containing plasma fluid. However, the main lesion was diagnosed as cemento-ossifying fibroma (COF), and the atypical vascular channels were greatly dilated and gradually expanded the whole tumor mass. The present COF was examined through immunohistochemical (IHC) array, and investigated for tumor cell characteristics, exhibiting abnormal ossification and aneurysmal cystic changes. IHC array disclosed that the tumor cells grew progressively in the lack of apoptosis, and that they showed lower expression of RUNX2 than BMP-2, RANKL, and OPG, and increases of protein expression in $HIF-1{\alpha}$, VEGF-A, and CMG2. These data suggested that the reduced expression of RUNX2, osteoblast differentiation factor, be relevant to abnormal ossification of COF, and that the consistent expressions of angiogenesis factors be relevant to de novo angiogenesis in COF, subsequently resulted in aneurysmal cystic changes.

• Clinical and Experimental Pediatrics
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• v.62 no.2
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• pp.55-61
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• 2019

Purpose: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK ) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. Methods: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats (<1,000 vs. ${\geq}1,000$). Results: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. Conclusion: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.7
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• pp.977-987
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• 2019

Objective: The use of tannin extract and other phytochemicals as dietary additives in ruminants is becoming more popular due to their wide biological actions such as in methane mitigation, bypass of dietary protein, intestinal nematode control, among other uses. Unfortunately, some have strong astringency, low stability and bioavailability, and negatively affecting dry matter intake and digestibility. To circumvent these drawbacks, an effective delivery system may offer a promising approach to administer these extracts to the site where they are required. The objectives of this study were to encapsulate acacia tannin extract (ATE) with native starch and maltodextrin-gum arabic and to test the effect of encapsulation parameters on encapsulation efficiency, yield and morphology of the microparticles obtained as well as the effect on rumen in vitro gas production. Methods: The ATE was encapsulated with the wall materials, and the morphological features of freeze-dried microparticles were evaluated by scanning electron microscopy. The in vitro release pattern of microparticles in acetate buffer, simulating the rumen, and its effect on in vitro gas production was evaluated. Results: The morphological features revealed that maltodextrin/gum-arabic microparticles were irregular shaped, glossy and smaller, compared with those encapsulated with native starch, which were bigger, and more homogenous. Maltodextrin-gum arabic could be used up to 30% loading concentration compared with starch, which could not hold the core material beyond 15% loading capacity. Encapsulation efficiency ranged from $27.7%{\pm}6.4%$ to $48.8%{\pm}5.5%$ in starch and $56.1%{\pm}4.9%$ to $64.8%{\pm}2.8%$ in maltodextrin-gum arabic microparticles. Only a slight reduction in methane emission was recorded in encapsulated microparticles when compared with the samples containing only wall materials. Conclusion: Both encapsulated products exhibited the burst release pattern under the pH conditions and methane reduction associated with tannin was marginal. This is attributable to small loading percentages and therefore, other wall materials or encapsulation methods should be investigated.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.184-194
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• 2021

Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

• Animal Bioscience
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• v.34 no.8
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• pp.1365-1374
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• 2021

Objective: This study was conducted to investigate the synergistic effect of exogenous multienzyme and phytase on growth performance, nutrients digestibility, blood metabolites, intestinal microflora, and morphology in broilers fed corn-wheat-soybean meal diets. Methods: A 2×2 factorial design was used in this study. Four dietary treatments consisted of i) basal diets (corn-wheat-soybean meal based diets without multi-enzyme and phytase), ii) basal diets with phytase (0.05%), iii) basal diets with exogenous multi-enzyme (0.05%), and iv) basal diets with exogenous multi-enzyme including phytase (0.05%). A total of 480 broiler chickens (Ross 308 - one day old) were weighed and allotted to thirty-two cages (15 birds per cage), and chicks were randomly allocated to four dietary treatments. Results: The body weight gain and feed conversion rate were improved by supplementation of exogenous multi-enzyme containing phytase during the finisher period (p<0.05). The birds fed diets with exogenous multi-enzyme containing phytase had a significantly greater digestibility of dry matter, gross energy, crude protein, calcium, and phosphorus compared with birds fed non-supplemented diets (p<0.05). The chickens fed diets with exogenous multi-enzyme containing phytase showed a higher concentration of Ca and P in the serum (p<0.05). The population of Lactobacillus spp., Escherichia coli, and Clostridium were not affected in the ileum and cecum of chickens fed enzyme-supplemented diets. The dietary supplemental exogenous multi-enzyme containing phytase showed a significant improvement in villus height, crypt depth, and villus height and crypt depth ratio, compared to basal diets or dietary supplemental phytase (p<0.05). Conclusion: The supplementation of the exogenous multi-enzyme containing phytase synergistically improved the growth performance, nutrients digestibility, and villus height of the small intestine of broiler chickens fed a corn-wheat-soybean meal based diets.

• Food Science of Animal Resources
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• v.41 no.5
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• pp.749-762
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• 2021

Colostrum, which contains various immune and growth factors, aids wound healing by promoting keratinocyte proliferation. Aquaporins (AQPs) are small, hydrophobic membrane proteins that regulate cellular water retention. However, few studies have examined the effect of processed colostrum whey on AQP-3 expression in human skin cells. Here, we investigated the effect of milk, colostrum, fermented milk, and fermented colostrum whey on AQP-3 expression in keratinocyte HaCaT cells. Concentrations of 100-400 ㎍/mL of fermented colostrum whey were found to induce HaCaT cell proliferation. AQP-3 was found to be expressed exclusively in HaCaT cells. AQP-3 expression was significantly increased in 100 ㎍/mL fermented colostrum whey-treated cells compared with that in controls. Moreover, fermented colostrum increased p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, but not ERK1/2 phosphorylation. Thus, our results suggest that fermented colostrum whey increased AQP-3 expression in, and the proliferation of, keratinocytes via JNK and p38 MAPK activation.

• The Korean Journal of Food And Nutrition
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• v.35 no.1
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• pp.7-15
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• 2022

Maca roots (Lepidium meyenii) are an important medicinal herb that have long been used by the Andes-indigenous peoples and South Americans. In Korea, recently, it has attracted attention as a health food material because of nutritional values and physiological activities. The purpose of this study was to investigate the industrial applicability of maca (red and golden varieties; R&G) as immunostimulating materials. In the macrophage stimulating assay using RAW 264.7 cells at 125~500 ㎍/mL of non-cytotoxicity doses, G-HW showed the most potent production of TNF-α, IL-6 and nitric oxide compared to red maca or the other extracts. The general component analysis results showed that all extracts comprised more than 90% neutral sugars with small amounts of uronic acid and protein. Meanwhile, component sugar analysis showed the difference in the content of uronic acids of cold- and hot-water extract. Additionally, the further fractionation of G-HW into crude polysaccharide (G-CP) greatly enhanced the macrophage stimulating activity, and G-CP contained macromolecules over 144 kDa, comprised mainly of glucose and galacturonic acid (51.0 and 34.9%). In conclusion, crude polysaccharide from maca showed industrial applicability as immunostimulating material, and especially golden maca showed higher macrophage stimulating activity than red maca.