• Biomolecules & Therapeutics
• /
• 제27권3호
• /
• pp.283-289
• /
• 2019

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

• 한방재활의학과학회지
• /
• 제29권2호
• /
• pp.101-113
• /
• 2019

Objectives Bogol-tang has clinically been used to protect joint cartilage and to treat osteoarthritis. Our objective was to study the protective effect of Bogol-tang extract (BGT) in functional impairment, behavioral disorders, cartilage loss and pathological changes in a monoiodoacetate (MIA)-induced murine osteoarthritis (OA) model and interleukin (IL)-$1{\beta}$ -treated primary rat chondrocytes. Methods Mouse knee joints were injected with MIA, a chemical that inhibits glycolysis and causes joint inflammation and matrix loss. MIA-OA induced mice orally administered BGT or acetaminophen (AAP) for 18 days by daily. Primary rat chondrocytes were pretreated with BGT or dexamethasone (DEX) and followed by co-incubation with IL-$1{\beta}$ (10 ng/mL). Results In MIA-OA mice model, BGT led to delayed response on hot plate analysis, and suppressed the cartilage loss and damages in joint tissues. BGT suppressed the elevated levels of inflammatory mediators, nitrite and $PGE_2$, the gene expression of matrix degrading enzymes, and extracellular-signal-regulated kinases 1/2 and c-JunN-terminal kinase phosphorylation in IL-$1{\beta}$-treated primary rat chondrocytes. Conclusions Our results suggest that BGT improve the knee joint function and delay the cartilage damages by anti-nociceptive, anti-inflammatory and ant-catabolic effects, which indicate BGT could be a potential candidate for osteoarthritis treatment.

• 대한의용생체공학회:의공학회지
• /
• 제42권6호
• /
• pp.268-276
• /
• 2021

Functional near-infrared spectroscopy-based brain-computer interface (fNIRS-based BCI) has been receiving much attention. However, we are practically constrained to obtain a lot of fNIRS data by inherent hemodynamic delay. For this reason, when employing machine learning techniques, a problem due to the high-dimensional feature vector may be encountered, such as deteriorated classification accuracy. In this study, we employ an elastic net-based feature selection which is one of the embedded methods and demonstrate the utility of which by analyzing the results. Using the fNIRS dataset obtained from 18 participants for classifying brain activation induced by mental arithmetic and idle state, we calculated classification accuracies after performing feature selection while changing the parameter α (weight of lasso vs. ridge regularization). Grand averages of classification accuracy are 80.0 ± 9.4%, 79.3 ± 9.6%, 79.0 ± 9.2%, 79.7 ± 10.1%, 77.6 ± 10.3%, 79.2 ± 8.9%, and 80.0 ± 7.8% for the various values of α = 0.001, 0.005, 0.01, 0.05, 0.1, 0.2, and 0.5, respectively, and are not statistically different from the grand average of classification accuracy estimated with all features (80.1 ± 9.5%). As a result, no difference in classification accuracy is revealed for all considered parameter α values. Especially for α = 0.5, we are able to achieve the statistically same level of classification accuracy with even 16.4% features of the total features. Since elastic net-based feature selection can be easily applied to other cases without complicated initialization and parameter fine-tuning, we can be looking forward to seeing that the elastic-based feature selection can be actively applied to fNIRS data.

• 한국동물생명공학회지
• /
• 제37권2호
• /
• pp.121-129
• /
• 2022

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an N6-methyladenosine (m⁶A) RNA modification regulator and a key determinant of prem-RNA processing, mRNA metabolism and transportation in cells. Currently, m⁶A reader proteins such as hnRNPA2/B1 and YTHDF2 has functional roles in mice embryo. However, the role of hnRNPA2/B1 in porcine embryogenic development are unclear. Here, we investigated the developmental competence and mRNA expression levels in porcine parthenogenetic embryos after hnRNPA2/B1 knock-down. HhnRNPA2/B1 was localized in the nucleus during subsequent embryonic development since zygote stage. After hnRNPA2/B1 knock-down using double stranded RNA injection, blastocyst formation rate decreased than that in the control group. Moreover, hnRNPA2/B1 knock-down embryos show developmental delay after compaction. In blastocyste stage, total cell number was decreased. Interestingly, gene expression patterns revealed that transcription of Pou5f1, Sox2, TRFP2C, Cdx2 and PARD6B decreased without changing the junction protein, ZO1, OCLN, and CDH1. Thus, hnRNPA2/B1 is necessary for porcine early embryo development by regulating gene expression through epigenetic RNA modification.

• 한국환경성돌연변이발암원학회지
• /
• 제23권2호
• /
• pp.56-62
• /
• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• Archives of Plastic Surgery
• /
• 제50권4호
• /
• pp.432-442
• /
• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

• 한국멀티미디어학회논문지
• /
• 제14권1호
• /
• pp.54-75
• /
• 2011

PoC(Push-to-talk Over Cellular)는 그룹 음성 및 영상 통화와 인터넷, 멀티미디어 서비스를 통합한 단말 기술이다. PoC는 부재, 긴급 상황, 배터리 방전 등과 같은 다양한 이유로 인해 PoC 세션에 참여하지 못하는 사용자에게 종래 MMS 서비스에서의 MM Box와 비슷한 기능을 가진 PoC Box를 사용하는 기능을 제공하고 있다. PoC 표준안에서는 PoC Box에서 PoC 단말로 미디어 전송 시 RTSP (Real-Time Streaming Protocol)를 사용하도록 권장하고 있다. 기존의 RTSP를 적용한 VOD 서비스의 경우는 빠른 유선 네트워크 망을 고려하여 패킷의 크기를 크게 구현하는 반면 PoC 서비스는 무선 통신 환경이기 때문에 이러한 특성을 고려한 RTSP 전송 방법이 필요하다. 무선 통신 환경에서는 패킷의 손실률이 비교적 유선 통신 환경에서보다 다소 높기 때문에 PoC 단말 측에서 미디어 재생 시 화면 끊김 현상, 영상과 음성의 비동기화 발생, 버퍼링 대기 시간 등이 발생한다. 따라서 PoC 단말 측에서의 이러한 문제점은 사용자가 미디어 콘텐츠를 재생하는데 있어 자신이 원하는 정보를 빠르게 습득하기 어렵게 만든다. 본 논문에서는 RTSP를 이용하여 사용자가 미디어 검색 시 단시간 내에 전송되는 미디어에서 효과적으로 중요한 정보를 습득하고 재생 지연 현상을 줄일 수 있는 "교차 이중 수신 버퍼링 기법", "사전 분할 다중 수신 버퍼링 기법", "On-Demand 다중 수신 버퍼링 기법"과 전송 시 미디어 데이터의 패킷화 방법인 "동일 순위 패킷화 전송 방식", "우선 순위 패킷화 전송 방식"을 제안하였고 실험을 통해 그 성능의 적정성 및 우수성을 검증하였다. 실시된 시뮬레이션 성능 평가에서 사용자의 미디어 검색 성향에 따라 제안된 다중 수신 버퍼링 및 패킷화 방식이 기존 단일 수신 버퍼링 방식과 비교하여 효율성 및 우수성 평가에서 6-9점 이상 우수한 결과를 보였다. 그 중 On-Demand 다중 수신 버퍼링 기법은 동일순위 패킷화 방법과 사용될 때 타 기법과 비교하여 3-24점 사이의 우수성을 보임으로써 사용자의 다양한 미디어 검색 성향에 대해 빠르게 대응할 수 있었다. 또한 단시간 내에 사용자가 집중적으로 미디어 검색이 이루어지는 재생 시간대에 대해 많은 미디어 데이터를 수신 받기 때문에 단말 사용자에게 빠른 정보를 제공할 수 있었다.

• 한국미생물·생명공학회지
• /
• 제44권2호
• /
• pp.156-162
• /
• 2016

본 연구에서는 신규 해양성 한천분해균을 분리하고, 이 균주가 생성하는 한천분해효소의 특성을 조사하였다. 경상남도 남해군 미조면 연안에서 채취한 해수를 Marine agar 2216 배지에 도말하여 한천분해세균을 선별하였다. 선택된 한천분해균주는 16S rDNA 염기서열분석을 통해 Maribacter 속 세균과 99% 유사하여 Maribacter sp. SH-1으로 명명하였다. 세포외로 분비되는 agarase는 Maribacter sp. SH-1 균주 배양액에서 획득하였으며, 이를 이용하여 특성을 조사하였다. Maribacter sp. SH-1 균주의 한천분해효소는 20, 30, 40, 50 및 60℃ 에서 각각 56, 62, 94, 100, 8%의 상대활성을 나타냈으며, pH 5, 6, 7 및 8에서 각각 15, 100, 60, 21%의 상대활성을 나타냈다. 세포외 agarase는 50℃ , pH 6인 20 mM Tris-HCl buffer를 사용하는 조건에서 최대활성(231 units/l)을 보였다. 한천이 sol 상태로 존재하는 50℃에서 최적활성을 보여 이 효소는 응용 가능성이 높다고 할 것이다. 효소 활성은 20, 30 및 40℃에서 30분 동안 열처리하였을 때 약 90% 이상의 상대활성을 보였다. TLC 분석 결과, Maribacter sp. SH-1 균주의 한천분해효소는 한천올리고당인 neoagarohexaose (34.8%), neoagarotetraose (52.2%) 및 neoagarobiose (13.0%)를 생성하는 것으로 보아 β-agarase로 확인되었다. 따라서 Maribacter sp. SH-1 균주와이 균주가 생산하는 β-agarase는 보습효과, 미백효과, 세균성장 억제 혹은 전분노화 방지 등의 기능을 가지는 한천올리고당의 생산에 유용할 것으로 기대된다.

• 한국발생생물학회지:발생과생식
• /
• 제2권2호
• /
• pp.165-171
• /
• 1998

p62는 임파구에 특이적으로 발현하는 단백질 티로신 키나제인 p56$^{lck}$의 SH2 doamin과 결합하는 세포질 단백질로서 두 단백질의 결합에는 지금까지 알려진 바와 다르게 인산화된 티로신이 필요없다. p62는 기능이 다른 여러 조직에서 공통적으로 발현되며 유비퀴틴, 단백질 키나제 C 이성질체 둥 다양한 단백질과 결합하는 것이 알려져 있다. 이와 같은 현상으로 p62가 다양한 생물학적 기능을 수행할 수 있음을 예측할 수 있으나 그 자세한 기작은 잘 알려져 있지 않다. 본 연구에서는 p62가 T-세포에 특이적으로 발현하는 14-3-3 $ au$ 이성질체와 결합하는 것을 확인하였으며, p62를 인위적으로 T-세포에 다량으로 발현시키면 세포예정사 (apoptosis)의 시작이 지연되는 현상을 조사하였다. 이때 세포사멸과정에서 전형적으로 나타나는 DNA 절단현상 (DNA fragmentaion)과 poly (ADP-ribose) polymerase의 분해가 지연됨을 알 수 있었다. 최근 14-3-3 단백질이 임파구에서 세포예정사를 촉진시키는 기능을 가진 Bad와 결합함으로써 세포의 생존 신호 전달에 중요한 역할을 한다는 것이 보고된 바 있다. 따라서 본 연구의 결과는 T-세포의 활성으로 일어나는 사멸예정사 과정 중에 p62와 14-3-3 단백질에 의해 수행되는 조절 기작이 있음을 시사하고 있다.다.

• 의료법학
• /
• 제9권1호
• /
• pp.319-382
• /
• 2008

As a withdrawing care's study, the purpose of this study is searching about withdrawing care's acceptance and circumstances through Bora-mae hospital case(chapter 1). Withdrawing life-sustaining treatment has various forms. Though the meaning of euthanasia, death with dignity, natural death, physician assisted suicide are duplicated, the meaning of those are different slightly. Firstly, this study looks about the difference of the those meaning and acceptance range(condition) by withdrawing care's forms(chapter 2). Bora-mae hospital case sentenced guilty about physician who discharged incompetent patient who was after surgery by patient's wife determination. This Bora-mae case that sentenced guilty about discharge against medical advise(DAMA) that is regarded to custom has brought intensive confliction of legal, social, medical aspect, Bora-mae hospital case has many legal problems. First, as to criminal law rule 250(murder), the problem is whether discharge and withdrawing life-sustaining treatment is commission or omission. this study concluded omission(district court: omission, appeal, supreme court: commission). Because legal denounce point of discharge and medical treatment withdrawing is omission that physician who is obligatory on patient to cure. If physician's act is regarded omission, it is necessary to determine whether he has guardian status and obligation. Without guardian status and obligation, omission crime can't exist. This study decided that physician had guardian status and obligation and foundation of guardian status was pre-action or acceptance of emergency patient. Physician's medical treatment duty finished when patient(or patient's guardian) demands discharge. But when patient death is foreseen and other possible treatment does not exist, his duty of life prolonging treatment does not finish. This originate from physician's social responsibility and public status that limits patient's private liberty. This study regarded physician's action as accomplice about whether physician's discharging action is accomplice or the principal offender(district court: the principal offender, appeal, supreme court: accomplice). Though the principal offender needs criminal determination and action, there is no this common determination and functional action control of physician in Bora-mae case(chapter 3). Bora-mae hospital case partly originated from deficiency of legal, institutive system including medical security system shortage, the instruction is 1. medical security system strengthening, 2. hospital ethical committee's activity strengthening, 3. institutionalization of withdrawing life-sustaining treatment, 4. acceptance of pre-decision making system, 5. sufficient persuasion of physician for patient and faithful writing of medical paper, 6. respect for patients' self-determination and rights, 7. consciousness's changing for withdrawing life-sustaining treatment and persistent education about medical ethics(chapter 4). Considering Bora-mae case, medical sector is not the dead ground of a criminal punishment. Intervention of criminal law in medical sector give rise to ill effect, that is, excess medical examination and treatment, safeguard treatment, delay of discharge from a hospital. Because sufficient guarantee of life becomes mere empty slogan under situation that impose a burden of heavy cost to family or hospital, public and systematic solution should be given(chapter 5).