• 제목/요약/키워드: nuclear transplantation

검색결과 104건 처리시간 0.026초

NF-κB and Therapeutic Approach

  • Lee, Chang-Hoon;Kim, Soo-Youl
    • Biomolecules & Therapeutics
    • /
    • 제17권3호
    • /
    • pp.219-240
    • /
    • 2009
  • Since NF-${\kappa}B$ has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of ${\kappa}B$ (NF-${\kappa}B$) in inflammatory signaling for decades. The various molecular components of NF-${\kappa}B$ transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-${\kappa}B$ pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-${\kappa}B$ signaling pathway for many therapeutic applications. However, a gene knock-out study for $IKK{\beta}$ in the NF-${\kappa}B$ pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte $IKK{\beta}$ accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of $IKK{\beta}$ appears to be beneficial to reduce HCC. This article will update issues of the NF-${\kappa}B$ pathway and inhibitors regulating this pathway.

방사선 사고와 급성 방사선 증후군 (Radiological Accident and Acute Radiation Syndrome)

  • 노형근
    • 대한임상독성학회지
    • /
    • 제9권2호
    • /
    • pp.39-48
    • /
    • 2011
  • In mass casualty situation due to radiological accidents, it is important to start aggressive management with rapid triage decisions. External contamination needs immediate decontamination and internal contamination should be treated with special expertise and equipment to prevent the rapid uptake of radionuclides by target organs. Acute radiation syndrome shows a sequence of events that varies with the severity of the exposure. More severe exposures generally lead to more rapid onset of symptoms and severe clinical findings. After the massive exposure, various systems of the body reflect their severe damages that can lead to death within hours or up to several months. The disease progression has classically been divided into four stages: prodromal, latent, manifest illness, and recovery or death. Three characteristic clusters of symptoms including the hematopoietic syndrome, the gastrointestinal syndrome and the cerebrovascular syndrome are all associated with the acute radiation syndrome. The standard medical management of the patients with a potentially survivable radiation exposure includes good medical, surgical and supportive measures. Specific treatment with cytokines and bone marrow transplantation should be considered. The management of internal contamination is much the same as the treatment of poisoning. The standard decontamination should be applied to reduce uptake, and the chelating agents can be administered to enhance the clearance of radioisotopes. Radioactive iodine ($^{131}I$) as one of the nuclear fission products can increase the incidence of thyroid cancer in children. Potential benefit of potassium iodide prophylaxis is greater especially in neonates, infants and small children.

  • PDF

체외생산 소 초기배 할구세포의 Embedding Matrix에서의 발생능력 (Development Ability of Bovine Early Embryo Blastomere In Vitro in Embedding Matrix)

  • 이홍준;서승운;이상호;송해범
    • 한국수정란이식학회지
    • /
    • 제10권2호
    • /
    • pp.171-175
    • /
    • 1995
  • This study was performed to establish the condition and the methods for the techniques of insertion the isolated blastomere cells into cytoplasm, in order to research the develop-mental ability of bovine embryo blastomere cells in vitro produced. After 24h in vitro ovary maturation with the ovaries from a slaughter house, in vitro fertilization was performed to the vital sperms which their mobility were decided by percoll gradient method, with 2~8 cell stage embryos, the blastomeres were isolated in $Ca^2$+. $Mg^2$+-free PBS, and following that embedded into agar and alginate solution, respectively. The rates of in vitro develop-ment are as follows ; in agar embedded 11 among 120(9.2%) 1 /2~1 /3 blastomers cleaved and 6 among 93(6.5%) 1 /4~1 /8 blastomeres cleaved. In sodium alginate-embedded 14 among 84(16.7%) 1 /2~1 /3 blastomeres cleaved and 6 among 85(7.1%) 1 /4~1 /8 blastomeres cleaved. In case of Na-alginate, the rate of the cells were better than those of agar. The results suggest that the techniques for embeeding the isolated blastomeres into gel may help cloning of bovine early embryo without nuclear transplantation.

  • PDF

Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases

  • Kim, Ju-Yeon;Choi, Haena;Kim, Hyeon-Ji;Jee, Yelin;Noh, Minsoo;Lee, Mi-Ock
    • Biomolecules & Therapeutics
    • /
    • 제30권5호
    • /
    • pp.391-398
    • /
    • 2022
  • Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

Nanosphere Form of Curcumin Stimulates the Migration of Human Umbilical Cord Blood Derived Mesenchymal Stem Cells

  • Kim, Do-Wan;Kim, Ju Ha;Lee, Sei-Jung
    • 한국환경과학회:학술대회논문집
    • /
    • 한국환경과학회 2020년도 정기학술대회 발표논문집
    • /
    • pp.221-221
    • /
    • 2020
  • Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases. In the present study, we found the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) during the wound closure. We found that the efficacy of hUCB-MSCs migration induced by CN was 1000-fold higher than that of curcumin powder. CN significantly increased the motility of hUCB-MSCs by activating c-Src, which is responsible for the phosphorylation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). CN induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhances wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

  • PDF

Reproductive ability of minipigs as surrogates for somatic cell nuclear transfer

  • Joonho Moon;Su-Jin Kim;Jinseok Lee;Hyeyoung Kang;Bumrae Cho;Sung Joo Kim
    • Journal of Animal Science and Technology
    • /
    • 제66권1호
    • /
    • pp.156-166
    • /
    • 2024
  • Pigs are genetically, anatomically, and physiologically similar to humans. Recently, pigs are in the spotlight as a suitable source animal for xenotransplantation. However, to use pigs as source animals, pigs should be raised in designated pathogen-free facilities. There is abundant data from embryo transfer (ET) experiments using farm pigs as surrogates, but data on ET experiments using minipigs are scarce. Eighty minipigs were used for ET experiments and after transplantation, the implantation and delivery rates were investigated. It was also confirmed whether the pregnancy rate could be increased by changing the condition or surgical method of the surrogate. In the case of minipigs that gave birth, the size of the fetal sac on the 28th day of ET was also measured. The factors that can affect the pregnancy rate such as estrus synchronization program, ovulation status at the time of ET, the number of repeated ET surgeries, and the ET sites, were changed, and the differences on the pregnancy rate were observed. However there were no significant differences in pregnancy rate in minipigs. The diameter of the implanted fetal sac on the 28th day after ET in the minipigs whose delivery was confirmed was calculated to be 4.7 ± 0.5 cm. In conclusion, there were no significant differences in pregnancy rate of minipigs in the comparative experiment on various factors affecting the pregnancy rate. However, additional experiments and analyses are needed due to the large individual differences of the minipigs.

생쥐 수정란의 핵이식에 관한 연구 II. 발달단계별 수정란 핵의 이식후 생존성 (Studies on nuclear transplantation in mouse embryos II. Developmental potential of nuclei from embryos of different developmental stages)

  • 박충생;최상용;이효종;박희성
    • 대한수의학회지
    • /
    • 제30권4호
    • /
    • pp.355-360
    • /
    • 1990
  • 포유동물의 초기 발생단계에서 핵의 분화와 전능성(totipotency) 을 규명하고, 수정란의 cloning technique를 개발하여 우량유전자로 조성된 개체를 복제함으로써 효과적인 종축개량 기법으로 응용하기 위하여 생쥐 수정란을 모델로 하여 미세조작기법과 Sendai virus를 이용한 핵융합기술을 이용하여 인위적으로 동일한 유전자를 가진 복제 수정란을 작출하고 이들의 작출효과, 체외발달능력 및 체내 이식후 개체발생여부 등을 조사하였다. 2-세포기, 4-세포기 및 8-세포기의 수정란으로부터 핵을 채취하여 이들을 탈핵된 2-세포기의 수정란에 이식하였을 때, 이들의 핵융합 성공율은 각각 88.6%, 87.1% 및 84.7%이었다. 나아가서 이들 핵융합된 수정란을 체외에서 96시간 배양한 결과, 2-세포기, 4-세포기 및 8-세포기의 핵이 이식된 수정란은 각각 76.5%, 68.4% 및 48.3%가 배반포로 발달하였다. 핵이식 후 체외에서 배반포로 발달된 수정란을 골라 수란생쥐에 이식하였던 바, 2-세포기의 핵이 이식된 수정란 156개 중 58개(37.1%) 가 발달하여 신생자로 생산되었으며, 4-세포기의 핵아 이식된 수정란 135개 중 40개(29.6%)가, 그리고 8-세포기의 핵이 이식된 92개의 수정란 중 15개(16.3%)가 신생자로 생산되었다.

  • PDF

확률 뇌 지도를 이용한 뇌 영역의 위치 정보 추출 (Probabilistic Anatomical Labeling of Brain Structures Using Statistical Probabilistic Anatomical Maps)

  • 김진수;이동수;이병일;이재성;신희원;정준기;이명철
    • 대한핵의학회지
    • /
    • 제36권6호
    • /
    • pp.317-324
    • /
    • 2002
  • 목적: SPM 기법을 이용하여 뇌 영상을 분석할 때 Talairach 뇌 지도를 찾아 해부학적 정보를 추측함으로 생기는 문제점들을 해결하기 위하여 통계적 확률 뇌지도(SPAM)을 이용하여 뇌 영역에 대한 해부학적 위치와 확률을 추출하는 프로그램을 개발하였다. 대상 및 방법: 몬트리얼 신경과학연구소에서 개발한 MNI152 표준지도에 기반한 SPAM을 이용하였다. SPM 분석 결과로 주어진 x, y, z 좌표 값을 입력하면 SPAM의 해당 좌표에서 0이 아닌 확률 값을 갖는 영역의 이름 및 확률을 추출하여 출력하게 하였으며 가장 높은 확률을 갖는 영역의 SPAM을 표준지도 위에 표시하도록 하였다. IDL 및 자바를 기반으로 프로그램을 개발하였으며 향후 인터넷 기반 프로그램으로 확장이 용이하게 하였다. 이 프로그램의 유용성을 보이고자 기존의 SPM 결과보고 형식과 이 프로그램의 결과 형식을 비교하였다. 또한 이 프로그램에 대한 예비적인 검증을 위하여 활성화되는 영역이 국소화되고 또한 그 영역이 잘 알려져 있는 기억 활성화 PET 실험 분석에 이 프로그램을 이용하여 보았다. 결과: 기존의 SPM 분석한 결과는 MNI 좌표계에서의 좌표 값만을 보여주나 이 프로그램을 이용하여 그 좌표에 대한 확률적 해부학적 정보를 얻을 수 있었다. 기억 실험 결과 유의한 활성화를 보인 영역에 대해서 이 프로그램을 적용한 결과 좌측해마구성체일 확률이 80% 이상임을 알 수 있었으며 이는 이 영역이 기억기능을 담당한다는 기존의 널리 알려진 사실과 잘 부합되었다. 결론: 이 연구에서 개발한 프로그램을 이용하여 MNI 좌표에 대한 해부학적 위치와 확률을 빠르고 정확하게 찾을 수 있어서 뇌영상 분석에 유용할 것이다.

인체 지방 유래 중간엽 줄기세포의 골분화 조절 기전에서 NFAT5의 역할 (Role of NFAT5 in Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells)

  • 이선영;양지원;정진섭
    • 생명과학회지
    • /
    • 제23권4호
    • /
    • pp.471-478
    • /
    • 2013
  • 인체 중간엽 줄기세포는 다양한 세포로의 분화 및 자가증식 할 수 있는 능력뿐만 아니라 질병치료에 대한 치료적 잠재력을 가지고 있다. 줄기세포 분화의 분자 기작에 대한 이해는 줄기세포 이식의 치료 효능을 향상시킨다. 본 연구에는 인체 중간엽 줄기세포의 골분화에서 NFAT5의 역할을 밝혔다. 특이적 siRNA의 transfection으로 인한 NFAT5의 억제는 인체 중간엽 줄기세포의 골분화를 현저히 감소시켰으며, NF-${\kappa}B$ promoter 활성화 또한 세포의 증식이나 지방 세포로의 분화에 영향 없이 감소 시켰다. NFAT5의 발현 억제는 기본적으로 유도되는 NF-${\kappa}B$의 활성화와 TNF-${\alpha}$에 의해서 유도되는 NF-${\kappa}B$의 활성화를 감소시켰으나, TNF-${\alpha}$에 의해서 유도되는 NF-${\kappa}B$의 분해에는 아무런 영향을 주지 않았다. 이번 연구를 통해 NFAT5가 NF-${\kappa}B$ 경로를 조절함으로써 인체 중간엽 줄기 세포의 골분화에 아주 중요한 역할을 하는 것을 확인 할 수 있었다.

지브라물고기 복제방법에 의한 유전자 동정 및 유전자트랩법 개발 (Developing a Gene-trapping Approach for Gene Identification Using Nuclear Transfer in Zebrafish)

  • 이기영
    • Journal of Animal Science and Technology
    • /
    • 제46권2호
    • /
    • pp.155-164
    • /
    • 2004
  • 이 연구는 gene-trap construct를 가지고 있는 배양세포로부터 trap gene을 확인하고 클로닝한 다음 이러한 세포를 이용하여 복제 지브라물고기를 만들기 위해 수행되어졌다. 본 연구에서 gene-trap과 연관된 복제 지브라물고기가 성공적으로 만들어졌다. 본 실험에서 두 종류의 백터(SA/GFP-TP와 Neo-TP)가 사용되었다. 이들 벡터에 의해 전이된 모든 종류의 세포는 항생제에 의해 선별을 하여 분석에 이용하였다. SA/GFP-TP에 의해 전이된 세포의 경우, 단일세포상에서 GFP 발현도가 낮아 본 연구에서 동물복제에 사용되지 않았으며, Neo-TP에 의해 전이된 세포주가 복제실험에 이용되었다. Neo-TP 세포에 의한 복제실험 결과, 총 1179개의 핵치환 난으로부터 44(3.7%) 개의 배자가 포배기에 도달하였으며, 8(0.8%) 개의 배자가 부화시기에 이르렀다. 그리고 3마리는 성숙단계에 이르렀으며, 이중 1마리에서 정상적으로 gene-trap 전이가 이루어짐을 Southern blot 분석을 통해 확인되었다.