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Development of Cell Therapeutics against Ischemic Vascular Diseases Using Mesenchymal Stem Cells: From Bench to Bed (중간엽줄기세포(MSC)를 이용한 허혈성 혈관질환 치료를 위한 세포치료제 개발: 기초연구에서 임상연구)

  • Lee, Eun Ji;Park, Shin Hu;Seo, Jeong Ho;An, Hyo Gyung;Nam, Si Hyun;Kwon, Sang-Mo
    • Journal of Life Science
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    • v.32 no.7
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    • pp.567-577
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    • 2022
  • Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.

Protective Effects of Medicinal Herbal Mixture (HME) through Akt/FoxO3 Signal Regulation in Oxidative Damaged C2C12 Myotubes (C2C12 myotube의 산화적 손상에 대한 혼합 한약재 추출물(HME)의 Akt/FoxO3 신호 조절을 통한 보호 효과)

  • Kim, So Young;Choi, Moon-Yeol;Lee, Un Tak;Choo, Sung Tae;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.37 no.4
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    • pp.31-38
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    • 2022
  • Objectives : In this study, we investigated the synergistic protective effects of medicinal herbal mixture (HME) including Mori Ramulus (MR), Acanthopanacis Cortex (AC), Eucommiae Cortex (EC), and Black soybean (BS) in C2C12 cells, mouse myoblasts. Methods : Effects of HME on cell viability of C2C12 myoblasts were monitored by MTT assay. Anti-atrophic activity of HME was determined in myoblasts and myotubes under oxidative stress by H2O2. C2C12 myoblasts were differentiated into myotubes in a medium containing 2% horse serum for 6 days. After that, we measured that expression of MyoD and myogenine, the myogenic regulatory factors, to identify the mechanism of inhibiting muscle atophy after HME treatment. In addition, suppression of phosphorylation of Akt, FoxO3a and MARF-1, transcription factors of degradation proteins were analyzed via western blotting. Results : As a result of MTT, HME there was no show cytotoxicity up to a concentration of 1 mg/ml. The cytoprotective effects on oxidative stressed myoblast and myotube was better in HME extract than those of MR, AC, EU, and BS, respectively. HME treatment in Myotube induced by oxidative stress after H2O2 treatment increased Myo D, Myogenine activation, and Akt, FoxO3a phosphorylation and decreased expression of MuRF-1. As the results, HME has synergistic effects on protection against proteolysis of C2C12 myotubes through activation of the Akt signaling pathway under oxidative stress. Conclusions : These results suggest that HME may also be useful as a preventing and treating material for skeletal muscle atrophy caused by age-related diseases.

Core Promoter Mutation of ntC1731T and G1806A of Hepatitis B Virus Increases HBV Gene Expression (B형 간염 바이러스의 ntC1731T 및 G1806A의 core 프로모터 돌연변이에 의한 HBV 유전자 발현 증가 분석)

  • Cho, Ja Young;Yi, Yi Kyaw;Seong, Mi So;Cheong, JaeHun
    • Journal of Life Science
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    • v.32 no.2
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    • pp.94-100
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    • 2022
  • Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

Cloning and Functional Studies of Pro-Apoptotic MCL-1ES BH3M (세포사멸을 유도하는 새로운 단백질인 MCL-1ES BH3M의 클로닝 및 기능연구)

  • Kim, Jae-Hong;Park, Mira;Ha, Hye-Jeong;Lee, Kangseok;Bae, Jeehyeon
    • Development and Reproduction
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    • v.12 no.3
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    • pp.297-303
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    • 2008
  • BCL-2 family members are essential protein for the regulation of cell death and survival consisting both antiapoptotic and pro-apoptotic proteins. In the present study, we designed and cloned a new apoptotic molecule MCL-1ES BH3M coding a modified protein of MCL-1L. Compared to MCL-1L protein, MCL-1ES BH3M lacks the PEST motifs known to be involved in MCL-1L protein degradation and has seven mutated residues in BH3 domain critical for dimerization with BCL-2 family members. Overexpression of MCL-1ES BH3M induced death of different cells, and its cell killing effect was not blocked by forced expression of the pro-survival protein MCL-1L. Expression of MCL-1ES BH3M protein led to the activation of caspase 9 and caspase 3, suggesting apoptotic cell death, and confocal fluorescent microscopic analyses showed that MCL-1ES BH3M was partially localized in mitochondria. In conclusion, we reported a new apoptotic molecule and determined its cell death activity in cells.

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Criminal Law Issues and Challenges Due to Changes in the Healthcare Paradigm (헬스케어 패러다임 변화에 따른 형사법적 쟁점과 과제)

  • Sun, JongSoo
    • The Korean Society of Law and Medicine
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    • v.24 no.1
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    • pp.43-65
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    • 2023
  • The healthcare industry is a digital healthcare that combines technology based on the 4th Industrial Revolution, dealing with information on individual health and medical care, and is a fusion of health care services and medical science and technology. It is questionable whether digital healthcare according to the paradigm change can be discussed by the concept of medical practice under the existing Medical Act. There is no clear definition of the concept of medical practice in the Medical Service Act, but the concept is established through precedents. In addition, under the Medical Service Act, the subject of medical practice is limited to medical personnel. However, digital healthcare sometimes diagnoses and treats diseases using digital technology by medical personnel. On the other hand, what is possible by non-medical personnel is digital healthcare. This is because digital healthcare is understood as a concept that includes health care such as exercise, eating habits, and weight control. For this reason, if the concept of medical practice under the "Medical Act" on digital healthcare is included, it is subject to criminal punishment for "unlicensed medical practice" prescribed in Article 27 of the "Medical Act". In the health and medical industry, digital transformation and convergence with information and communication technology are rapidly progressing. As a result, there is a need to newly define it as 'digitalized medical practice' or 'information and communication technology (ICT)-based medical practice' separately from existing medical practices. The concept of medical practice has variability, not a fixed and invariable concept. However, in response to this demand, it is not an infinite expansion of the concept of medical practice, but a request to reset its scope. Therefore, the concept of medical practice should be legislated by reflecting the demand of consumers for the medical service system.

Improving CO2 Adsorption Performance of Activated Carbons Treated by Plasma Reaction with Tetrafluoromethane (사불화탄소 플라즈마 반응에 의해 처리된 활성탄소의 CO2 흡착 성능 향상)

  • Chung Gi Min;Chaehun Lim;Seo Gyeong Jeong;Seongjae Myeong;Young-Seak Lee
    • Applied Chemistry for Engineering
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    • v.34 no.2
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    • pp.170-174
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    • 2023
  • CO2 is known as one of the causes of global warming, and various studies are being conducted to capture it. In this study, a tetrafluoromethane (CF4) plasma reaction was performed to improve the CO2 adsorption of activated carbons (ACs) through changes in surface characteristics, and the adsorption characteristics according to the reaction time were considered. After the reaction, the micropore volume increased up to 1.03 cm3/g. In addition, as the reaction time increased, the fluorine content on the surface increased to 0.88%. It was possible to simultaneously control the pore properties and surface functional groups of the ACs through this experiment. Also, the CO2 uptake of surface-treated ACs improved up to 7.44% compared to untreated ACs, showing the best performance at 3.90 mmol/g when the reaction time was 60 s. This is due to the synergy effect of the fluorine functional groups introduced on the surface of the ACs and the increased micropore volume caused by the etching effect. It was found that the micropore volume had a greater effect on CO2 adsorption in the region where the CO2 uptake was less than 3.67 mmol/g, while the added fluorine content had a greater effect in the region above that.

Optimization of In vitro Cultures for Production of Seedling and Rootstock of Rehmannia glutinosa(Gaertn.) DC. (지황 배양묘 및 종근 생산을 위한 기원검증 및 최적기내배양조건 확립)

  • Kang, Young Min;Lee, Ka Youn;Kim, Mi Sun;Choi, Ji Eun;Moon, Byeong Cheol
    • Journal of agriculture & life science
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    • v.50 no.5
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    • pp.81-93
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    • 2016
  • Rehmannia glutinosa(Gaertn.) DC. is a herbaceous perennial plant and belonging to the Scrophulariaceae and used as roots for medicinal part and purpose. R. glutinosa is and usually used for fresh rehmannia root or prepared rehmannia root. However, it is very difficult to propagate using the seeds because of lack germination so it is propagated using the vegetative method as the rootstock. Currently, propagation and harvesting using the rootstock of R. glutinosa has difficulties about production of the high quality and quantity in R. glutinosa because of root rot disease. To optimize in vitro cultures and to improve the rootstock and seedling of R. glutinosa after morphological and genetical determination, 5 plant culture media (MS, DJ, LS, QL, and WPM) were used in this study then WPM was selected for better growth, for multiplication condition(WPM + IAA 1.0 mg/L + IBA 0.5 mg/L), and for root enlargement condition(WPM + NAA 0.1 mg/L) of R. glutinosa. Based on these results, in vitro seedlings of R. glutinosa were transferred to soil for acclimation with environment adaptation and shown the positive effects about root enlargement and root formation. Therefore, it can be used for high quality of R. glutinosa production and production of the rootstock based on propagation using in vitro seedlings of R. glutinosa.

The measurement of dicamba in soil and plants (토양 및 식물 중 디캄바 측정법에 대한 연구)

  • Shin, Ho-Sang
    • Analytical Science and Technology
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    • v.22 no.6
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    • pp.480-487
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    • 2009
  • The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) in soil and plants was determined by gas chromatography-mass spectrometry (GC/MS). The samples were extracted with diethyl ether at pH 2, and washed with 0.1 N HCl, and then dried. The dried residue was derivatized in 1 mL of 10% $H_2SO_4$-MeOH for 2 hr at $80^{\circ}C$. The reaction mixture was neutralized with 4 mL of sodium bicarbonate solution and reextracted with 5 mL of diethyl ether. After the extract was concentrated, dicamba was determined by GC/MS-SIM mode. There was good linearity above 0.999 in the ranges of the $1.0{\sim}100{\mu}g/kg$. Total 42 sample including 32 soil samples and 10 plants samples were analyzed by developed method. Dicamba was detected in the concentration range of $2.9-123.9{\mu}g/kg$ in 15 samples among 32 soil samples and in the concentration range of $43-33,252{\mu}g/kg$ in 5 samples among 10 plants samples. A cause of the wither and die of the pine trees is suspected to spray dicamba around or directly to them.

A Study on the Leaching and Recovery of Lithium by Reaction between Ferric Chloride Etching Solution and Waste Lithium Iron Phosphate Cathode Powder (폐리튬인산철 양극재 분말과 염화철 에칭액과의 반응에 의한 리튬의 침출 및 회수에 대한 연구)

  • Hee-Seon Kim;Dae-Weon Kim;Byung-Man Chae;Sang-Woo Lee
    • Resources Recycling
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    • v.32 no.3
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    • pp.9-17
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    • 2023
  • Efforts are currently underway to develop a method for efficiently recovering lithium from the cathode material of waste lithium iron phosphate batteries (LFP). The successful application of lithium battery recycling can address the regional ubiquity and price volatility of lithium resources, while also mitigating the environmental impact associated with both waste battery material and lithium production processes. The isomorphic substitution leaching process was used to recover lithium from spent lithium iron phosphate batteries. Lithium was leached by the isomorphic substitution of Fe2+ in LFP using a relatively inexpensive ferric chloride etching solution as a leaching agent. In the study, the leaching rate of lithium was compared using the ferric chloride etching solution at various multiples of the LFP molar ratio: 0.7, 1.0, 1.3, and 1.6 times. The highest lithium leaching rate was shown at about 98% when using 1.3 times the LFP molar ratio. Subsequently, to eliminate Fe, the leachate was treated with NaOH. The Fe-free solution was then used to synthesize lithium carbonate, and the harvested powder was characterized and validated. The surface shape and crystal phase were analyzed using SEM and XRD analysis, and impurities and purity were confirmed using ICP analysis.

Simulation of Vehicle-Structure Dynamic Interaction by Displacement Constraint Equations and Stabilized Penalty Method (변위제한조건식과 안정화된 Penalty방법에 의한 차량 주행에 따른 구조물의 동적상호작용 해석기법)

  • Chung, Keun Young;Lee, Sung Uk;Min, Kyung Ju
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.26 no.4D
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    • pp.671-678
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    • 2006
  • In this study, to describe vehicle-structure dynamic interaction phenomena with 1/4 vehicle model, nonlinear Hertzian contact spring and nonlinear contact damper are adopted. The external loads acting on 1/4 vehicle model are selfweight of vehicle and geometry information of running surface. The constraint equation on contact surface is implemented by the Penalty method with stabilization and the reaction from constraint violation. To describe pitching motion of various vehicles two types of the displacement constraint equations are exerted to connect between car bodies and between bogie frames, i.e., the rigid body connection and the rigid body connection with pin, respectively. For the time integration of dynamic equations of vehicles and structure Newmark time integration scheme is adopted. To reduce the error caused by inadequate time step size, adaptive time-stepping technique is also adopted. Thus, it is expected that more versatile dynamic interaction phenomena can be described by this approach and it can be applied to various railway dynamic problems with low computational cost.