• Title/Summary/Keyword: molecular design

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Effect of Ghrelin on Memory Impairment in a Rat Model of Vascular Dementia (그렐린이 혈관성 치매 쥐의 기억 손상에 미치는 효과)

  • Park, Jong-Min;Kim, Youn-Jung
    • Journal of Korean Academy of Nursing
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    • v.49 no.3
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    • pp.317-328
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    • 2019
  • Purpose: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. Methods: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered $80{\mu}g/kg$ ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. Results: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. Conclusion: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

  • Kim, Nayoung;Lee, Dong-Hee;Choi, Woo Seon;Yi, Eunbi;Kim, HyoJeong;Kim, Jung Min;Jin, Hyung-Seung;Kim, Hun Sik
    • BMB Reports
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    • v.54 no.1
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    • pp.44-58
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    • 2021
  • Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

Development SCAR marker for the rapid authenticaton of Sinomeni Caulis et Rhizoma based on ITS Sequences (ITS 염기서열 기반 방기 신속 감별용 SCAR marker 개발)

  • Kim, Wook Jin;Noh, Sumin;Choi, Goya;Moon, Byeong Cheol
    • The Korea Journal of Herbology
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    • v.37 no.4
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    • pp.9-16
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    • 2022
  • Objectives : In the Korean Pharmacopoeia 12th edition (KP 12) and the Korean Herbal Pharmacopoeia (KHP), two authentic herbal medicines are described, namely Bang-gi (Cheong-pung-deung) and Mok-bang-gi, respectively. In China, Bun-bang-gi is also used as herbal medicine. This study was conducted to develop a molecular authentication tool for distinguishing the three herbal medicine used as Bang-gi, which are Sinomeni Caulis et Rhizoma (Rhizome of Sinomenium acutum), Stephaniae Tetrandrae Radix (Root of Stephania terandra), and Cocculi Radix (Root of Cocculus trilobus). Methods : Twelve samples of three species (four samples of S. acutum, five samples of S. tetrandra, and three samples of C. trilobus) were collected from different habitats. The sequences of internal transcribed spacer (ITS) regions were obtained and comparatively analyzed to design the species-specific sequence characterized amplified region (SCAR) primers. The specificity of each pair of SCAR primers that amplified species-specific amplicon was evaluated for establishing the singleplex and multiplex PCR assay tools. Results : The singleplex SCAR markers show discriminability in C. acutum, S. tetrandra, and C. trilobus. These SCAR markers were also efficiently authenticated three species in the multiplex SCAR amplification using single PCR reaction. Furthermore, these PCR assay methods were applicable to authenticate dried herbal medicines distributed in the markets. Conclusions : The SCAR markers and PCR assay tools help discriminate the three herbal medicines used as Bang-gi at the species levels and provide a reliable genetic method to prevent the inauthentic distribution of these herbal medicines.

Chemosensitizing effect and mechanism of imperatorin on the anti-tumor activity of doxorubicin in tumor cells and transplantation tumor model

  • Liang, Xin-li;Ji, Miao-miao;Liao, Zheng-gen;Zhao, Guo-wei;Tang, Xi-lan;Dong, Wei
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.3
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    • pp.145-155
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    • 2022
  • Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

Emerging Research Advancements to Overcome the Peach Spring Frost

  • Pandiyan Muthuramalingam;Rajendran Jeyasri;Yeonju Park;Seongho Lee;Jae Hoon Jeong;Yunji Shin;Jinwook Kim;Sangmin Jung;Hyunsuk Shin
    • Research in Plant Disease
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    • v.29 no.3
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    • pp.220-233
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    • 2023
  • The phenomena of global warming has led to an increase in the average air temperature in temperate climates. Springtime frost damage is becoming more common, and after a period of dormancy, damage to buds, blooms, and developing fruits is greater significant than damage from low winter temperatures. Peaches are a crucial crop among moderate fruits. Spring frost damage in peaches can have a negative effect on crop growth, yield, and quality. It is noteworthy that these plants have evolved defenses against spring frost damage while being exposed to a variety of low temperatures in the early spring. In this current review, recent research advancements on spring frost damage avoidance in peaches were deliberated. Additionally, adaptive mechanisms of peach, such as deacclimation and reacclimation, were emphasized. Moreover, the emerging advancements using various omics approaches revealed the peach physiology and molecular mechanisms comprehensively. Furthermore, the use of chemical products and understanding the spring frost mechanisms through the use of environmental chamber temperature stimulation and infrared thermography studies were also discussed. This review is essential groundwork and paves the way to derive and design future research for agronomists and horticulturalists to overcome the challenges of spring frost damage avoidance and crop management in these circumstances.

Effect of Heat Treatment on Mechanical Properties of Cross-Linked Ultra-High Molecular Weight Polyethylene Used for Artificial Joint Liner (인공관절 라이너용 가교된 초고분자량폴리에틸렌(UHMWPE)의 열처리 조건에 따른 기계적 특성 변화)

  • Kim, Hyun-Mook;Kim, Dong-Hoon;Gu, Ja-Uk;Choi, Nak-Sam;Kim, Sung-Kon
    • Composites Research
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    • v.22 no.2
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    • pp.1-6
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    • 2009
  • The mechanical characteristics of gamma-ray irradiated UHMWPE specimens were investigated under various heat treatment conditions. The heat treatment was performed in the range of annealing and remelting temperatures. The annealing treatment below the temperature of $130^{\circ}C$ hardly induced changes in the tensile strength, the strain at the failure and the hardness. However the remelting treatment above $140^{\circ}C$ deteriorated those mechanical properties. It was shown in an FTIR analysis that the annealing treatment caused some oxidation of free radicals created by the pretreatment of the irradiation. These quantitative data represented by the behavior of mechanical properties might be used as basic informations for the design and analysis of various artificial joints.

Effect of dietary betaine supplementation on the liver transcriptome profile in broiler chickens under heat stress conditions

  • Deok Yun Kim;Gi Ppeum Han;Chiwoong Lim;Jun-Mo Kim;Dong Yong Kil
    • Animal Bioscience
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    • v.36 no.11
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    • pp.1632-1646
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    • 2023
  • Objective: The objective of the present study was to investigate the effect of dietary betaine (BT) supplementation on the hepatic transcriptome profiles in broiler chickens raised under heat stress (HS) conditions. Methods: A total of 180 (21-d-old) Ross 308 male broiler chicks were allotted to 1 of 3 treatment groups with 6 replicated cages in a completely randomized design. One group was kept under thermoneutral conditions at all times and was fed a basal diet (PC). Other 2 groups were exposed to a cyclic heat stress condition. One of the 2 groups under heat stress conditions was fed the basal diet as a negative control (NC), whereas the other group was fed the basal diet supplemented with 0.2% BT. All chickens were provided with diets and water ad libitum for 21 d. Following the experiment, the liver samples were collected for RNA sequencing analysis. Results: Broiler chickens in NC and BT group had decreased (p<0.05) growth performance. In the transcriptome analysis, the number of differentially expressed genes were identified in the liver by HS conditions and dietary BT supplementation. In the comparison between NC and PC treatments, genes related to energy and nucleic acid metabolism, amino acid metabolism, and immune system were altered by HS, which support the reason why heat-stressed poultry had decreased growth performance. In the comparison between NC and BT treatments, genes related to lipid metabolism, carbohydrate metabolism, and immune system were differently expressed under HS conditions. Conclusion: HS negatively impacts various physiological processes, including DNA replication, metabolism of amino acids, lipids, and carbohydrates, and cell cycle progression in broiler chickens. Dietary BT supplementation, however, offers potential counteractive effects by modulating liver function, facilitating gluconeogenesis, and enhancing immune systems. These findings provide a basis for understanding molecular responses by HS and the possible benefits of dietary BT supplementation in broiler chickens exposed to HS.

The cumulative survival rate of sandblasted, large-grit, acid-etched dental implants: a retrospective analysis

  • Haeji Yum;Hee-seung Han;Kitae Kim;Sungtae Kim;Young-Dan Cho
    • Journal of Periodontal and Implant Science
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    • v.54 no.2
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    • pp.122-135
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    • 2024
  • Purpose: This retrospective study aimed to assess the long-term cumulative survival rate of titanium, sandblasted, large-grit, acid-etched implants over a 10-year follow-up period and investigate the factors affecting the survival rate and change in marginal bone loss (MBL). Methods: The study included 400 patients who underwent dental implant placement at the Department of Periodontology of Seoul National University Dental Hospital (SNUDH) between 2005 and 2015. Panoramic radiographic images and dental records of patients were collected and examined using Kaplan-Meier analysis, Cox proportional hazards regression analysis, and multiple regression analysis to determine the survival rates and identify any factors related to implant failure and MBL. Results: A total of 782 implants were placed with a follow-up period ranging from 0 to 16 years (mean: 8.21±3.75 years). Overall, 25 implants were lost, resulting in a cumulative survival rate of 96.8%. Comparisons of the research variables regarding cumulative survival rate mostly yielded insignificant results. The mean mesial and distal MBLs were 1.85±2.31 mm and 1.59±2.03 mm, respectively. Factors influencing these values included age, diabetes mellitus (DM), jaw location, implant diameter, bone augmentation surgery, and prosthetic unit. Conclusions: This study found that the implant survival rates at SNUDH fell within the acceptable published criteria. The patients' sex, age, DM status, implant location, implant design, implant size, surgical type, bone augmentation, and prosthetic unit had no discernible influence on long-term implant survival. Sandblasted, large-grit, acid-etched implants might offer advantages in terms of implant longevity and consistent clinical outcomes.

Novel Anti-Mesothelin Nanobodies and Recombinant Immunotoxins with Pseudomonas Exotoxin Catalytic Domain for Cancer Therapeutics

  • Minh Quan Nguyen;Do Hyung Kim;Hye Ji Shim;Huynh Kim Khanh Ta;Thi Luong Vu;Thi Kieu Oanh Nguyen;Jung Chae Lim;Han Choe
    • Molecules and Cells
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    • v.46 no.12
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    • pp.764-777
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    • 2023
  • Recombinant immunotoxins (RITs) are fusion proteins consisting of a targeting domain linked to a toxin, offering a highly specific therapeutic strategy for cancer treatment. In this study, we engineered and characterized RITs aimed at mesothelin, a cell surface glycoprotein overexpressed in various malignancies. Through an extensive screening of a large nanobody library, four mesothelin-specific nanobodies were selected and genetically fused to a truncated Pseudomonas exotoxin (PE24B). Various optimizations, including the incorporation of furin cleavage sites, maltose-binding protein tags, and tobacco etch virus protease cleavage sites, were implemented to improve protein expression, solubility, and purification. The RITs were successfully overexpressed in Escherichia coli, achieving high solubility and purity post-purification. In vitro cytotoxicity assays on gastric carcinoma cell lines NCI-N87 and AGS revealed that Meso(Nb2)-PE24B demonstrated the highest cytotoxic efficacy, warranting further characterization. This RIT also displayed selective binding to human and monkey mesothelins but not to mouse mesothelin. The competitive binding assays between different RIT constructs revealed significant alterations in IC50 values, emphasizing the importance of nanobody specificity. Finally, a modification in the endoplasmic reticulum retention signal at the C-terminus further augmented its cytotoxic activity. Our findings offer valuable insights into the design and optimization of RITs, showcasing the potential of Meso(Nb2)-PE24B as a promising therapeutic candidate for targeted cancer treatment.

Effects of supplemental bacteriophage on the gut microbiota and nutrient digestibility of ileal-cannulated pigs

  • Hyunwoong Jo;Geongoo Han;Eun Bae Kim;Changsu Kong;Beob Gyun Kim
    • Journal of Animal Science and Technology
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    • v.66 no.2
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    • pp.340-352
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    • 2024
  • This study measured the potential changes of the microbiota in the gastrointestinal tract and energy and nutrient digestibility by supplemental bacteriophages in pigs. Twelve castrated male pigs (initial mean body weight = 29.5 ± 2.3 kg) were surgically cannulated using T-cannula. The animals were housed individually in pens equipped with a feeder and a nipple waterer. The pigs were allotted to 1 of 3 experimental diets in a quadruplicated 3 × 2 Latin square design with 3 experimental diets, 2 periods, and 12 pigs resulting in 8 replicates per diet. The 3 diets were a control mainly based on corn and soybean meal with no antibiotics or bacteriophages, a diet containing 0.1% antibiotics, and a diet containing 0.2% bacteriophages. On day 5 of the experimental period, feces were collected and on days 6 and 7, ileal digesta were collected. Genomic DNA for bacteria were extracted from the ileal digesta and feces and the V4 region of the 16S rRNA gene was amplified. The ileal and fecal digestibility of energy, dry matter, organic matter, crude protein, and fiber was unaffected by dietary antibiotics or bacteriophages. At the phylum level, the supplemental antibiotic or bacteriophage tended to result in a higher proportion of Firmicutes (p = 0.059) and a lower proportion of Bacteroidetes (p = 0.099) in the ileal digesta samples compared with the control group with no difference between the antibiotic and bacteriophage groups. At the genus level, the supplemental antibiotic or bacteriophage tended to result in a higher proportion of Lactobacillus (p = 0.062) and a lower proportion of Bacteroides (p = 0.074) and Streptococcus (p = 0.088) in the ileal digesta compared with the control group with no difference between the antibiotic and bacteriophage groups. In the feces, supplemental antibiotics or bacteriophages reduced the proportion of Bifidobacterium compared with the control group (p = 0.029) with no difference between the antibiotic and bacteriophage groups. Overall, supplemental antibiotics and bacteriophages showed positive effect on the microbiota of in the ileal digesta without largely affecting energy or nutrient digestibility, with no differences between the antibiotic and bacteriophage groups in growing pigs.