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The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2

  • Li, Yuxia;Bai, Hua;Zhang, Zhongzu;li, Weihua;Dong, Lei;Wei, Xueju;Ma, Yanni;Zhang, Junwu;Yu, Jia;Sun, Guotao;Wang, Fang
    • Molecules and Cells
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    • v.37 no.3
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    • pp.213-219
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    • 2014
  • MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

Development of 3D Printed Snack-dish for the Elderly with Dementia (3D 프린팅 기술을 활용한 치매노인 전용 영양(수분)보충 식품섭취용기 개발)

  • Lee, Ji-Yeon;Kim, Cheol-Ho;Kim, Kug-Weon;Lee, Kyong-Ae;Koh, Kwangoh;Kim, Hee-Seon
    • Korean Journal of Community Nutrition
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    • v.26 no.5
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    • pp.327-336
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    • 2021
  • Objectives: This study was conducted to create a 3D printable snack dish model for the elderly with low food or fluid intake along with barriers towards eating. Methods: The decision was made by the hybrid-brainstorming method for creating the 3D model. Experts were assigned based on their professional areas such as clinical nutrition, food hygiene and chemical safety for the creation process. After serial feedback processes, the grape shape was suggested as the final model. After various concept sketching and making clay models, 3D-printing technology was applied to produce a prototype. Results: 3D design modeling process was conducted by SolidWorks program. After considering Dietary reference intakes for Koreans (KDRIs) and other survey data, appropriate supplementary water serving volume was decided as 285 mL which meets 30% of Adequate intake. To consider printing output conditions, this model has six grapes in one bunch with a safety lid. The FDM printer and PLA filaments were used for food hygiene and safety. To stimulate cognitive functions and interests of eating, numbers one to six was engraved on the lid of the final 3D model. Conclusions: The newly-developed 3D model was designed to increase intakes of nutrients and water in the elderly with dementia during snack time. Since dementia patients often forget to eat, engraving numbers on the grapes was conducted to stimulate cognitive function related to the swallowing and chewing process. We suggest that investigations on the types of foods or fluids are needed in the developed 3D model snack dish for future studies.

Development of a prototype simulator for dental education (치의학 교육을 위한 프로토타입 시뮬레이터의 개발)

  • Mi-El Kim;Jaehoon Sim;Aein Mon;Myung-Joo Kim;Young-Seok Park;Ho-Beom Kwon;Jaeheung Park
    • The Journal of Korean Academy of Prosthodontics
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    • v.61 no.4
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    • pp.257-267
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    • 2023
  • Purpose. The purpose of the study was to fabricate a prototype robotic simulator for dental education, to test whether it could simulate mandibular movements, and to assess the possibility of the stimulator responding to stimuli during dental practice. Materials and methods. A virtual simulator model was developed based on segmentation of the hard tissues using cone-beam computed tomography (CBCT) data. The simulator frame was 3D printed using polylactic acid (PLA) material, and dentiforms and silicone face skin were also inserted. Servo actuators were used to control the movements of the simulator, and the simulator's response to dental stimuli was created by pressure and water level sensors. A water level test was performed to determine the specific threshold of the water level sensor. The mandibular movements and mandibular range of motion of the simulator were tested through computer simulation and the actual model. Results. The prototype robotic simulator consisted of an operational unit, an upper body with an electric device, a head with a temporomandibular joint (TMJ) and dentiforms. The TMJ of the simulator was capable of driving two degrees of freedom, implementing rotational and translational movements. In the water level test, the specific threshold of the water level sensor was 10.35 ml. The mandibular range of motion of the simulator was 50 mm in both computer simulation and the actual model. Conclusion. Although further advancements are still required to improve its efficiency and stability, the upper-body prototype simulator has the potential to be useful in dental practice education.

Polymorphic Variation of Inflammation-related Genes and Risk of Non-Hodgkin Lymphoma for Uygur and Han Chinese in Xinjiang

  • Gu, Xia;Shen, Yan;Fu, Ling;Zuo, Hong-Yun;Yasen, Halida;He, Ping;Guo, Xin-Hong;Shi, Yu-Wei;Yusufu, Muhabaiti
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9177-9183
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    • 2014
  • Polymorphisms of inflammation-related genes have been found to be associated with non-Hodgkin lymphoma (NHL) or some of its subtypes, but only a few relevant data have been reported in China. In this study, the Snapshot method was used to assess genetic variation; a total of 14 single nucleotide polymorphisms (SNPs) for 6 inflammatory factors in 157 NHL cases (64 Uygur ethnic subjects, 93 Han Chinese) and 435 controls (231 Uygur and 204 Han Chinese) were studied from the Xinjiang province of China. Haplotype distribution was estimated using PHASE 2.3 software. Statistical differences in the genotype and haplotype frequencies between case and control groups were also considered and estimated. For the Han population, the geneotype distributions for TNF-${\alpha}rs1800629$, TNF-${\alpha}rs1800630$, IL-6 rs1800795, IL-6 rs1800797, NF-KB1 rs1585215 and TLR-4 rs4986790 showed significant differences between the case and control groups (p<0.05). The TNF-${\alpha}$ gene frequencies of ACG and CCA haplotypes in the cases were higher than in the controls (OR=2.45, 95% CI: 1.55-3.89, p=0.0002, OR=2.53, 95% CI: 1.10-5.80, p=0.029, respectively), and the same findings were detected for TNF-${\beta}$ gene CA haplotype (OR=1.87, 95% CI: 1.21-2.90, p=0.0054). However, for the Uygur population, no such significant differences were detected within the gene-type distribution of the 14 SNPs. The TNF-${\alpha}$ gene frequency of the CCA haplotype between the two groups (OR=1.98, 95% CI: 1.11-3.51, p=0.021) revealed a statistically significant difference. Our results showed that polymorphic variations of inflammation-related genes could be important to the NHL etiology of the Han population, and that these may only have limited influence on the Uygur population.

The Calcineurin-Drp1-Mediated Mitochondrial Fragmentation is Aligned with the Differentiation of c-Kit Cardiac Progenitor Cells

  • Attaur Rahman;Yuhao Li;Nur Izzah Ismail;To-Kiu Chan;Yuzhen Li;Dachun Xu;Hao Zhou;Sang-Bing Ong
    • International Journal of Stem Cells
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    • v.16 no.2
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    • pp.123-134
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    • 2023
  • Objective: The heart contains a pool of c-kit+ progenitor cells which is believed to be able to regenerate. The differentiation of these progenitor cells is reliant on different physiological cues. Unraveling the underlying signals to direct differentiation of progenitor cells will be beneficial in controlling progenitor cell fate. In this regard, the role of the mitochondria in mediating cardiac progenitor cell fate remains unclear. Specifically, the association between changes in mitochondrial morphology with the differentiation status of c-kit+ CPCs remains elusive. In this study, we investigated the relationship between mitochondrial morphology and the differentiation status of c-kit+ progenitor cells. Methods and Results: c-kit+ CPCs were isolated from 2-month-old male wild-type FVB mice. To activate differentiation, CPCs were incubated in α-minimal essential medium containing 10 nM dexamethasone for up to 7 days. To inhibit Drp1-mediated mitochondrial fragmentation, either 10 μM or 50 μM mdivi-1 was administered once at Day 0 and again at Day 2 of differentiation. To inhibit calcineurin, either 1 μM or 5 μM ciclosporin-A (CsA) was administered once at Day 0 and again at Day 2 of differentiation. Dexamethasone-induced differentiation of c-kit+ progenitor cells is aligned with fragmentation of the mitochondria via a calcineurin-Drp1 pathway. Pharmacologically inhibiting mitochondrial fragmentation retains the undifferentiated state of the c-kit+ progenitor cells. Conclusions: The findings from this study provide an alternative view of the role of mitochondrial fusion-fission in the differentiation of cardiac progenitor cells and the potential of pharmacologically manipulating the mitochondria to direct progenitor cell fate.

The protective effects of BMSA1 and BMSA5-1-1 proteins against Babesia microti infection

  • Yu Chun Cai;Chun Li Yang;Peng Song;Muxin Chen;Jia Xu Chen
    • Parasites, Hosts and Diseases
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    • v.62 no.1
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    • pp.53-63
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    • 2024
  • The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 ㎍/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0±3.0%, and 48.0±2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.

Hepatic Venous Return in Atrial Isomerism Evaluated by MR (심방 이성체 환자의 간정맥 환류에 대한 자기공명영상 소견)

  • 홍용국;박영환
    • Journal of Chest Surgery
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    • v.30 no.5
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    • pp.493-500
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    • 1997
  • We performed this study to evaluate hepatic venous drainage in atrial isomerism by MR and the clinical significance of anomalous hepatic venous return in total cavopulmonary shunt operation. Numbers and locations of hepatic veins in twenty-two patients with isomerism(thirteen with right isomerism and nine with left isom rism) were evaluated by MR. Operative procedure of hepatic veins and postoperative arterial oxygen saturation were compared with hepatic vein connection in six patients after total cavopulmonary shunt operation. Among nine patients with left isomerism, hepatic venous return was totally anomalous via a single opening in eight, and via two separate openings in one. Among thirteen patients with right isomerism, partial anomalous hepatic venous connection directly to the atrium was seen in four. One showed total anomalous hepatic venous connection to atrium through one opening. Total cavopulmonary shunt operation was performed in 6 patients. Hepatic veins were connected to pulmonary arteries in four patients who had one atrial opening of hepatic vein andlor IVC, or two ipsilateral atrial opening of hepatic veins and IVC. In conclusion, hepatic vein drainage to atrium is variable in atrial isomerism. MR is useful for evaluation of hepatic vein drainage in atrial isomerism and surgical pla ning.

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Local Drug Delivery System Using Biodegradable Polymers

  • Khang, Gil-Son;Rhee, John M.;Jeong, Je-Kyo;Lee, Jeong-Sik;Kim, Moon-Suk;Cho, Sun-Hang;Lee, Hai-Bang
    • Macromolecular Research
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    • v.11 no.4
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    • pp.207-223
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    • 2003
  • For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

Optimized study of an in vitro 3D culture of preantral follicles in mice

  • Hehe Ren;Yingxin Zhang;Yanping Zhang;Yikai Qiu;Qing Chang;Xiaoli Yu;Xiuying Pei
    • Journal of Veterinary Science
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    • v.24 no.1
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    • pp.4.1-4.16
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    • 2023
  • Background: In vitro culture of preantral follicles is a promising technology for fertility preservation. Objectives: This study aims to investigate an optimized three-dimensional (3D) fetal bovine serum (FBS)-free preantral follicle culture system having a simple and easy operation. Methods: The isolated follicles from mouse ovaries were randomly divided in an ultra-low attachment 96-well plates supplement with FBS or bovine serum albumin (BSA) culture or encapsulated with an alginate supplement with FBS or BSA culture. Meanwhile, estradiol (E2) concentration was assessed through enzyme-linked immunosorbent assay of culture supernatants. The diameter of follicular growth was measured, and the lumen of the follicle was photographed. Spindle microtubules of oocytes were detected via immunofluorescence. The ability of oocytes to fertilize was assessed using in vitro fertilization. Results: The diameters were larger for the growing secondary follicles cultured in ultra-low attachment 96-well plates than in the alginate gel on days 6, 8, and 10 (p < 0.05). Meanwhile, the E2 concentration in the BSA-supplemented medium was significantly higher in the alginate gel than in the other three groups on days 6 and 8 (p < 0.05), and the oocytes in the FBS-free system could complete meiosis and fertilization in vitro. Conclusions: The present study furnishes insights into the mature oocytes obtained from the 3D culture of the preantral follicle by using ultra-low attachment 96-well plate with an FBS-free system in vitro and supports the clinical practices to achieve competent, mature oocytes for in vitro fertilization.

A Study on Increased Properties of Cellulose-Based Biodegradable Polymer Composites (셀룰로오스 기반 생분해성 고분자 복합재의 물성 증가에 관한 연구)

  • Sangjun Hong;Ajeong Lee;Sanghyeon Ju;Youngeun Shin;Teahoon Park
    • Composites Research
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    • v.36 no.2
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    • pp.126-131
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    • 2023
  • Growing environmental concerns regarding pollution caused by conventional plastics have increased interest in biodegradable polymers as alternative materials. The purpose of this study is to develop a 100% biodegradable nanocomposite material by introducing organic nucleating agents into the biodegradable and thermoplastic resin, poly(lactic acid), to improve its properties. Accordingly, cellulose nanofibers, an eco-friendly material, were adopted as a substitute for inorganic nucleating agents. To achieve a uniform dispersion of cellulose nanofibers (CNFs) within PLA, the aqueous solution of nanofibers was lyophilized to maintain their fibrous shape. Then, they were subjected to primary mixing using a twin-screw extruder. Test specimens with double mixing were then produced by injection molding. Differential scanning calorimetry was employed to confirm the reinforced physical properties, and it was found that the addition of 1 wt% CNFs acted as a reinforcing material and nucleating agent, reducing the cold crystallization temperature by approximately 14℃ and increasing the degree of crystallization. This study provides an environmentally friendly alternative for developing plastic materials with enhanced properties, which can contribute to a sustainable future without consuming inorganic nucleating agents. It serves as a basis for developing 100% biodegradable green nanocomposites.