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Perioperative stress prolong post-surgical pain via miR-339-5p targeting oprm1 in the amygdala

  • Zhu, Yi;Sun, Mei;Liu, Peng;Shao, Weidong;Xiong, Ming;Xu, Bo
    • The Korean Journal of Pain
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    • v.35 no.4
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    • pp.423-432
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    • 2022
  • Background: The decreased expression of mu-opioid receptors (MOR) in the amygdala may be a key molecular in chronic post-surgical pain (CPSP). It is known that miR-339-5p expression in the amygdala of a stressed rat model was increased. Analyzed by RNAhybrid, miR-339-5p could target opioid receptor mu 1 (oprm1) which codes MOR directly. So, the authors hypothesized that miR-339-5p could regulate the expression of MOR via targeting oprm1 and cause the effects to CPSP. Methods: To simulate perioperative short-term stress, a perioperative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception rat model was built. A pmiR-RB-REPORTTM dual luciferase assay was taken to verify whether miR-339-5p could act on oprm1 as a target. The serum glucocorticoid level of rats was test. Differential expressions of MOR, GFAP, and pERK1/2 in each group of the rats' amygdala were tested, and the expressions of miR-339-5p in each group of rats' amygdalas were also measured. Results: Perioperative stress prolonged the recovery time of incision pain. The expression of MOR was down-regulated in the amygdala of rats in stress + incision (S + IN) group significantly compared with other groups (P < 0.050). miR-339-5p was up-regulated in the amygdala of rats in group S + IN significantly compared with other groups (P < 0.050). miR-339-5p acts on oprm1 3'UTR and take MOR mRNA as a target. Conclusions: Perioperative stress could increase the expression of miR-339-5p, and miR-339-5p could cause the expression of MOR to decrease via targeting oprm1. This regulatory pathway maybe an important molecular mechanism of CPSP.

Effects of Luteolin-7-𝑂-glucoside on melanin synthesis (Luteolin-7-𝑂-glucoside가 멜라닌 합성에 미치는 영향)

  • Choi, Byeong Min;Hong, Hyehyun;Park, Taejin;Kim, Seung-Young
    • Journal of Applied Biological Chemistry
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    • v.65 no.3
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    • pp.231-237
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    • 2022
  • Biorenovation is a method that converts existing compounds into new compounds through the enzymatic action of microorganisms. Biorenovation has expected effects such as reducing toxicity of compounds and increasing their activity. In this study, we successfully synthesized Luteolin-7-O-glucoside (L7G) through biorenovation and investigated its inhibitory effect on melanin production in α-Melanocyte stimulating hormone induced B16F10 mouse melanoma cells. We confirmed that Luteolin was toxic at 50, 100 and 200 µM, but our L7G in same concentration was not toxic for B16F10 mouse melanoma cells and also showed significant reduction in melanin production and tyrosinase activity. In addition, while investigating the effect of L7G on factors involved in melanin synthesis through western blotting, we were able to confirm that the MITF and tyrosinase protein synthesis was inhibited in treatment with L7G, however, tyrosinase related protein-1 (TRP-1) and dopachrome tautomerase (TRP-2) expression was not affected. So we derived a conclusion that through biorenovation we could produce compounds like L7G with improved activity and reduced toxicity for possible use as an active ingredient with whitening functionality in cosmetics.It also suggests that the application of biorenovation has potential usefulness in developing anti-inflammatory materials. It also suggests that the application of bio-renovation has potential usefulness in the development of inflammatory material. We applied Biorenovation technology to Distylium racemosum extract (DR) to generate Distylium racemosum biorenovation product (DRB), and investigated the anti-inflammatory properties of DRB in lipopolysaccharide (LPS)-treated RAW264.7 macrophages. We are applying technology to Biorenovation Distylium racemosum extract (DR) Distylium racemosum was to create a biorenovation product (DRB), lipopolysaccharide (LPS) investigated the anti-inflammatory properties of DRB in RAW264.7 macrophages treated for.

SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression

  • Kim, Hyungmin;Lee, Jeehan;Jung, Soon-Young;Yun, Hye Hyeon;Ko, Jeong-Heon;Lee, Jeong-Hwa
    • Molecules and Cells
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    • v.45 no.10
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    • pp.718-728
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    • 2022
  • Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

Allomyrina dichotoma larva extract attenuates free fatty acid-induced lipotoxicity in pancreatic beta cells

  • Kim, Kyong;Kwak, Min-Kyu;Bae, Gong-Deuk;Park, Eun-Young;Baek, Dong-Jae;Kim, Chul-Young;Jang, Se-Eun;Jun, Hee-Sook;Oh, Yoon Sin
    • Nutrition Research and Practice
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    • v.15 no.3
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    • pp.294-308
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    • 2021
  • BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

Adjuvant Chemotherapy in Patients with Node-Negative Non-Small Cell Lung Cancer with Satellite Pulmonary Nodules in the Same Lobe

  • Park, Jiyoun;Lee, Junghee;Jeon, Yeong Jeong;Shin, Sumin;Cho, Jong Ho;Kim, Hong-Kwan;Choi, Yong Soo;Kim, Jhingook;Zo, Jae Ill;Shim, Young Mog
    • Journal of Chest Surgery
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    • v.55 no.1
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    • pp.10-19
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    • 2022
  • Background: According to the eighth TNM (tumor-node-metastasis) staging system, the presence of separate tumor nodules in the same lobe is designated as a T3 descriptor. However, it remains unclear whether adjuvant chemotherapy confers survival advantages in this setting. Methods: We retrospectively identified 142 pathologic T3N0M0 patients with additional pulmonary nodules in the same lobe from a single-institutional database from 2004 to 2019. The main outcomes were overall survival and recurrence-free survival. Multivariable Cox regression was used to identify the benefit of adjuvant chemotherapy while adjusting for other variables. Results: Sixty-one patients received adjuvant chemotherapy (adjuvant group) and 81 patients did not receive adjuvant therapy after surgery (surgery-only group). There were no demonstrable differences between the 2 groups regarding hospital mortality and postoperative complications, indicating that treatment selection had not significantly occurred. However, the use of adjuvant chemotherapy was associated with improved 5-year overall survival (70% vs. 59%, p=0.006) and disease-free survival (60% vs. 46%, p=0.040). A multivariable Cox model demonstrated that adjuvant chemotherapy was associated with a survival advantage (adjusted hazard ratio, 0.54; p<0.001). In exploratory analyses of subgroups, the effect of adjuvant chemotherapy seemed to be insufficient in those with small main tumors (<4 cm). Conclusion: Adjuvant chemotherapy was associated with better survival in T3 cancers with an additional tumor nodule in the same lobe. However, the role of adjuvant chemotherapy in patient subgroups with small tumors or those without risk factors should be determined via large studies.

Antioxidant Activities of Korean Perilla Leaves (Perilla frutescens) by Various Cultivars (잎들깨 품종에 따른 추출물의 항산화 활성 및 생리활성 평가)

  • Hyun Young, Kim;HanGyeol, Lee;Hye Young, Seo;Woo Duck, Seo;Mi Ja, Lee;Seung-Yeob, Song;Jung In, Kim;June-Yeol, Choi
    • The Korean Journal of Food And Nutrition
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    • v.35 no.6
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    • pp.453-463
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    • 2022
  • This study aimed to investigate the biological activities, including polyphenolic content, flavonoid content, and antioxidant activities, of various cultivars of Korean perilla leaves. The results indicated that among nine cultivars (Namcheon dlggae, Saedora, Nulbora, Donggel 1, Donggell 2, Soim, Sangyeop, Somirang, and Saebom) of perilla leaves, the total polyphenolic content (gallic acid equivalent mg/g, GAE) was the highest in "Nulbora," while it was lowest in Namcheon dlggae. Moreover, flavonoid content in the extracts of nine cultivars leaves was in the range of 132.93~268.50 mg catechin equivalent/g sample. The antioxidant effects of the perilla leaves were determined using two different in vitro bioassays measuring DPPH and ABTS radical-scavenging activities. The results revealed that antioxidant activity was also higher in "Nulbora" compared with other cultivars. Xanthin-oxidase-inhibition activity ranged from 65.65% to 80.58%, with "Nulbora" exhibiting the highest activity, although the difference with other cultivars was not significant. "Nulbora" extracts reduced the expression of pro-inflammatory genes and several cytokines, including IL-6 activation induced by LPS in macrophages in the range of 100-50 ㎍/mL. These results suggest that extracts from perilla leaves can be used as bioactive and functional materials that could be important in industrial applications in the future.

Estimation Method of the Amount of Demolition Waste through Automated Calculation of Volumetric Spaces using Drones (드론 활용 체적산출 자동화를 통한 해체 폐기물량 예측기법에 관한 연구)

  • Ryu, Jung-Rim;Kim, Hye-Ri;Park, Won-Jun
    • Journal of the Korea Institute of Building Construction
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    • v.22 no.6
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    • pp.681-688
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    • 2022
  • In this study, the process of drone photography, automatic volume calculation, total floor area conversion, and waste calculation was constructed as a QGIS plug-in to predict the demolition waste (DW) generated in an aged area where drawing information or building information is uncertain. Through a case study, the high consistency between the automatically calculated volume using the drone and the BIM volume based on the field measurement was confirmed. Field application was carried out for the planned demolition work site, and the consistency between the drone-based volume and the actual measurement-BIM-based volume was reconfirmed. The waste generation unit was applied and the amount of DW was calculated by setting the floor height and building type, and the entire process was completed within 6 hours. Although the difference between building information and building objects through drones occurred according to the setting of temporary structures, loads, and floor heights, it was found that the actual amount of DW was generated more than the initial estimate. It is expected that measures to improve the accuracy of volume and floor area conversion will be required through case studies in the future.

Antimicrobial resistance studies in staphylococci and streptococci isolated from cows with mastitis in Argentina

  • Elisa, Crespi;Ana M., Pereyra;Tomas, Puigdevall;Maria V., Rumi;María F., Testorelli;Nicolas, Caggiano;Lucia, Gulone;Marta, Mollerach;Elida R., Gentilini;Mariela E., Srednik
    • Journal of Veterinary Science
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    • v.23 no.6
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    • pp.12.01-12.10
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    • 2022
  • Background: Staphylococcus aureus and Streptococcus agalactiae are the main cause of clinical mastitis in dairy cattle in Argentina, whereas coagulase-negative staphylococci (CNS) and environmental streptococci are the main cause of subclinical mastitis. Bacteria isolated from infected animals show increasing antimicrobial resistance. Objectives: This study aims to determine the antimicrobial resistance of staphylococci and streptococci isolated from milk with mastitis, and to genotypically characterize the methicillin-resistant (MR) staphylococci. Methods: Isolation was performed on blood agar and identification was based on biochemical reactions. Antimicrobial susceptibility was according to the Clinical and Laboratory Standards Institute guidelines. The antimicrobial resistance genes, SCCmec type and spa type were detected by the polymerase chain reaction method. Results: We isolated a total of 185 staphylococci and 28 streptococci from 148 milk samples. Among the staphylococcal isolates, 154 were identified as CNS and 31 as S. aureus. Among the 154 CNS, 24.6% (n = 38) were resistant to penicillin, 14.9% (n = 23) to erythromycin, 17.5% (n = 27) to clindamycin, 6.5% (n = 10) to cefoxitin and oxacillin. Among the S. aureus isolates, 16.1% (n = 5) were resistant to penicillin, 3.2% (n = 1) to cefoxitin and oxacillin (MRSA). Six MR isolates (5 CNS and 1 MRSA) were positive to the mecA gene, and presented the SCCmec IVa. The MRSA strain presented the sequence type 83 and the spa type 002. Among the 28 streptococcal isolates, 14.3% (n = 4) were resistant to penicillin, 10.7% (n = 3) to erythromycin and 14.3% (n = 4) to clindamycin. Conclusions: The present findings of this study indicate a development of antimicrobial resistance in main bacteria isolated from cows with mastitis in Argentina.

Antibacterial Effect of Sinhyowoldosan Against Methicillin-Resistant Staphylococcus aureus (신효월도산(神效越桃散)이 메티실린에 내성이 있는 Staphylococcus aureus에 대한 항균활성에 관한 연구)

  • Shin, In-Sik;Kang, Ok-Hwa;Joung, Dae-Ki;Kang, Hee-Jung;Kim, Ji-Eun;Hwang, Hyeong-Chil;Kim, In-Won;Kwon, Dong-Yeul
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.59-64
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    • 2013
  • Objectives : Methicillin-Resistant Staphylococcus aureus (MRSA) is a cephalosporin and beta-lactam antibiotic-resistant strains. In most cases, that is spread from infected patients and infection rates are growing increasingly. Thus, accordingly, increased resistance to antibiotics is causing serious problems in the world. Therefore, there is a need to develop alternative antimicrobial drugs for the treatment of infections diseases. Methods : The antibacterial activities of Sinhyowoldosan were evaluated against 3 strains of Methicillin-resistant staphylococcus aureus(MRSA) and 1 standard Methicillin-susceptible S. aureus (MSSA) strain by using the disc diffusion method, minimal inhibitory concentrations (MICs) assay, colorimetric assay using MTT test, checkerboard dilution test and time-kill assay was performed under dark. Results : The MIC (minimum inhibitory concentration) of Sinhyowoldosan water extract against S. aureus strains ranged from 500 to 2,000 ${\mu}g/mL$, so we have confirmed it on a strong antibacterial effect. Also, the combinations of Sinhyowoldosan water extract and conventional antibiotics exhibited improved inhibition of MRSA with synergy effect. We suggest that Sinhyowoldosan water extract against MRSA have antibacterial activity, it has potential as alternatives to antibiotic agent. the combination test was used, Triton X-100 (TX) and DCCD for measurement of membrane permeability and inhibitor of ATPase. As a result, antimicrobial activity of SH is affected by the cell membrane were assessed. Conclusion : We suggest that the Sinhyowoldosan water extract lead the treatment of bacterial infection to solve the resistance and remaining side-effect problems that are the major weak points of traditional antibiotics.

Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride (알코올 및 사염화탄소에 의해 유발된 급만성 간손상에 대한 지구자 열수추출물의 보호효과)

  • Kim, Young-Sik;Park, Juyeon;Kwon, Yongbeom;Lim, Dong Wook;Song, MiKyung;Choi, Ho-Young;Kim, Hocheol
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.25-32
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    • 2013
  • Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and $CCl_4$ in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute $CCl_4$-induced liver injury, rats received a single dose of $CCl_4$ (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after $CCl_4$ administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and ${\gamma}$-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and ${\gamma}$-GTP levels compared to control group. In acute $CCl_4$-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute $CCl_4$-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.