• 제목/요약/키워드: Ex vivo

검색결과 413건 처리시간 0.024초

Cochlear Implant Failure in the Pediatric Population

  • Ozer, Fulya;Yavuz, Haluk;Yilmaz, Ismail;Ozluoglu, Levent N.
    • 대한청각학회지
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    • 제25권4호
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    • pp.217-223
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    • 2021
  • Background and Objectives: In cochlear implant (CI) surgery, the results and causes of revision and reimplantation may guide surgeons in establishing surgical protocols for revision surgery with safe audiological outcomes. The aim of this study was to review our experience in terms of etiology, surgical strategy, and hearing outcomes in pediatric patients who underwent CI removal and reimplantation. Subjects and Methods: All patients received implants of the same brand. Pre and postoperative Categories of Auditory Performance score and aided free-field pure tone audiometry thresholds were noted. In vivo integrity tests were performed for each patient and the results of ex vivo tests of each implant were obtained from manufacturer. Results: A total of 149 CIs were placed in 121 patients aged <18 years. The revision rate in children was 6.7% (10/121 children). Six patients had a history of head injury leading to a hard failure. The causes of reimplantation in others were soft failure (n=1), electrode migration (n=1), infection (n=1), and other (n=1). All patients showed better or similar postreimplantation audiological performance compared with pre-reimplantation results. Conclusions: It is very important to provide a safe school and home environment and educate the family for reducing reimplantation due to trauma. Especially for active children, psychiatric consultation should be continued postoperatively.

Applications of CRISPR technologies to the development of gene and cell therapy

  • Chul-Sung Park;Omer Habib;Younsu Lee;Junho K. Hur
    • BMB Reports
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    • 제57권1호
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    • pp.2-11
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    • 2024
  • Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-to-thymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.

Mechanical Stretch-Induced Protection against Myocardial Ischemia-Reperfusion Injury Involves AMP-Activated Protein Kinase

  • Hao, Jia;Kim, Hun-Sik;Choi, Woong;Ha, Tae-Sun;Ahn, Hee-Yul;Kim, Chan-Hyung
    • The Korean Journal of Physiology and Pharmacology
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    • 제14권1호
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    • pp.1-9
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    • 2010
  • AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced myocardial infarct induced by ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate, acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the AMPK inhibitor, Compound C. AMPK activator (AICAR) mimicked SIC. Gadolinium, a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas diltiazem, a specific L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.

A Synthetic Tul4 and FopA Peptide Cocktail of Francisella tularensis Induces Humoral and Cell-Mediated Immune Responses in Mice

  • Oh, Hanseul;Kim, C-Yoon;Kim, Chang-Hwan;Hur, Gyeung-Haeng;Park, Jae-Hak
    • Journal of Microbiology and Biotechnology
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    • 제26권9호
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    • pp.1613-1619
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    • 2016
  • Francisella tularensis is a highly virulent pathogen of humans and other mammals. Moreover, F. tularensis has been designated a category A biothreat agent, and there is growing interest in the development of a protective vaccine. In the present study, we determine the in vitro and in vivo immune responses of a subunit vaccine composed of recombinant peptides Tul4 and FopA from epitopes of the F. tularensis outer membrane proteins. The recombinant peptides with adjuvant CpG induced robust immunophenotypic change of dendritic cell (DC) maturation and secretion of inflammatory cytokines (IL-6, IL-12). In addition, the matured DCs enabled ex vivo proliferation of naive splenocytes in a mixed lymphocyte reaction. Lastly, we determined the in vivo immune response by assessment of antibody production in C57BL/6 mice. Total IgG levels were produced after immunization and peaked in 6 weeks, and moreover, Tul4-specific IgG was confirmed in the mice receiving peptides with or without CpG. Based on these results, we concluded that the recombinant peptides Tul4 and FopA have immunogenicity and could be a safe subunit vaccine candidate approach against F. tularensis.

DIS에 의한 Polyethylene Glycol 함침 알로에 베라 겔의 보습 및 경피흡수 특성 (Moisturization and Transdermal Penetration Characteristics of PEGimpregnated Aloe vera Gel from DIS Processing)

  • 권혜미;허원;이신영
    • KSBB Journal
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    • 제28권5호
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    • pp.319-326
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    • 2013
  • This study was carried out to investigate the in vitro and in vivo moisturizing properties and percutaneous absorption of PEG-impregnated Aloe vera gel. The PEG-i-Aloe gel was obtained from dewatering and impregnation by soaking (DIS) of Aloe vera leaf slice. The moisturizing property of the obtained sample was evaluated by moisture determination using gravimetric method in desiccator under different RH% and by water sorption-desorption test on human skin. The transdermal penetration characteristics of PEG-i-Aloe gel was investigated by Franz diffusion cell in vitro transdermal absorption method. PEG-i-Aloe gel had high moisture retention ability and could significantly lead the enhancing skin hydration status as well as reducing the skin water loss due to the film formation as a skin barrier. The skin penetration rate of PEGi- Aloe gel at steady state was 9.76 ${\mu}g/(h{\cdot}cm^2)$ and the quantity of the transdermal absorption was 144 ${\mu}g/cm^2$ in 9 hr. The penetration mechanism was well fitted with Higuchi model ($R^2$ = 0.974-0.994). The results show that PEG-i-Aloe gel has the significant moisturizing effect and strong penetration of the animal skin. It could be used as the moisturizing additive in cosmetic skin products.

MK-801이 메트암페타민에 의한 도파민 신경독성에 미치는 효과: 메트암페타민에 의한 도파민 유리의 장기간 억제 (Effect of MK-801 on Methamphetamine-Induced Dopaminergic Neurotoxicity: Long-Term Attenuation of Methamphetamine-Induced Dopamine Release)

  • 김상은;김유리;황세환
    • 대한핵의학회지
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    • 제35권4호
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    • pp.258-267
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    • 2001
  • Purpose/Methods: Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum uslng $[^3H]$]WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Results: Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 mg/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4 mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. Conclusion: These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

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Water soluble tomato concentrate regulates platelet function via the mitogen-activated protein kinase pathway

  • Jeong, Dahye;Irfan, Muhammad;Saba, Evelyn;Kim, Sung-Dae;Kim, Seung-Hyung;Rhee, Man Hee
    • 대한수의학회지
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    • 제56권2호
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    • pp.67-74
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    • 2016
  • Tomato extract has been shown to exert antiplatelet activity in vitro and to change platelet function ex vivo, but with limitations. In this study, antiplatelet activity of water soluble tomato concentrate (Fruitflow I) and dry water soluble tomato concentrate (Fruitflow II) was investigated using rat platelets. Aggregation was induced by collagen and adenosine diphosphate and granule-secretion, $[Ca^{2+}]_i$, thromboxane B2, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were examined. The activation of integrin ${\alpha}_{IIb}{\beta}_3$ and phosphorylation of signaling molecules, including mitogen-activated protein kinase (MAPK) and PI3K/Akt, were investigated by flow cytometry and immunoblotting, respectively. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were examined. Moreover, in vivo thrombus weight was tested by an arteriovenous shunt model. Fruitflow I and Fruitflow II significantly inhibited agonist induced platelet aggregation, adenosine triphosphate and serotonin release, $[Ca^{2+}]_i$, and thromboxane B2 concentration, while having no effect on cAMP and cGMP levels. Integrin ${\alpha}_{IIb}{\beta}_3$ activation was also significantly decreased. Moreover, both concentrates reduced phosphorylation of MAPK pathway factors such as ERK, JNK, P38, and PI3K/Akt. In vivo thrombus formation was also inhibited. Taken together, these concentrates have the potential for ethnomedicinal applications to prevent cardiovascular ailments and can be used as functional foods.

과량의 아연에 노출된 생쥐의 사이토카인 생산에 미치는 인도메타신의 영향 (Effects of Indomethacin on the Production of Cytokines in Mice Exposed to Excessive Zinc)

  • 채병숙;신태용
    • 약학회지
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    • 제46권4호
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    • pp.258-264
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    • 2002
  • Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway

  • Park, Seul-Ki;Seong, Rak-Kyun;Kim, Ji-Ae;Son, Seok-Jun;Kim, Younghoon;Yokozawa, Takako;Shin, Ok Sarah
    • Nutrition Research and Practice
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    • 제10권1호
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    • pp.3-10
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    • 2016
  • BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.

Suspension culture system을 이용한 hematopoietic stem cell의 expansion

  • 권준;김미정;김병수;박홍우
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2001년도 추계학술발표대회
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    • pp.475-478
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    • 2001
  • 체외에서 hematopoietic cells의 배양은 필수이식으로 하여금 hematopoietic malignancies로 인해 고통받는 환자들을 치료할 수 있다. 본 실험에서는 골수의 초기 농도$1.5{\times}10^6cells/ml$로 하여 IL-3(5ng/ml), SCF(5ng/ml)과 FL(25ng/ml)의 성장 인자들을 첨가함으로써 bone marrow의 전체 cell의 증식은 생성시키지 못 했지만 LTC-IC는 3.6배의 증식을 가져왔다.

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