• BMB Reports
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• 제52권12호
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• pp.679-688
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• 2019

The decrease of metabolism in the brain has been observed as the important lesions of Alzheimer's disease (AD) from the early stages of diagnosis. The cumulative evidence has reported that the failure of mitochondria, an organelle involved in diverse biological processes as well as energy production, maybe the cause or effect of the pathogenesis of AD. Both amyloid and tau pathologies have an impact upon mitochondria through physical interaction or indirect signaling pathways, resulting in the disruption of mitochondrial function and dynamics which can trigger AD. In addition, mitochondria are involved in different biological processes depending on the specific functions of each cell type in the brain. Thus, it is necessary to understand mitochondrial dysfunction as part of the pathological phenotypes of AD according to each cell type. In this review, we summarize that 1) the effects of AD pathology inducing mitochondrial dysfunction and 2) the contribution of mitochondrial dysfunction in each cell type to AD pathogenesis.

• The Korean Journal of Physiology and Pharmacology
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• 제6권5호
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• pp.235-239
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• 2002

It has been reported that lovastatin induced cell death and suppressed proliferation in various cell lines. In this study, we examined whether the cytotoxic effects of lovastatin could be prevented by Bcl-2 or $Bcl-_{XL}$ in C6 glial cells. Overexpression of human Bcl-2 or $Bcl-_{XL}$ prevented lovastatin $(25{\mu}M)-induced$ changes such as DNA fragmentation, chromatin condensation, disruption of cell membrane, and cleavage of poly (ADP-ribose) polymerase. Lovastatin-induced inhibition of cell proliferation was unaffected by Bcl-2 or $Bcl-_{XL}$ overexpression. These results suggest that Bcl-2 and $Bcl-_{XL}$ can prevent lovastatin-induced apoptosis in C6 glial cells, though the inhibition of proliferation remains unaffected by these proteins.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.875-881
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• 2021

The mitochondrial targeting domain (MTD) of Noxa contributes to its mitochondrial localization and to apoptosis induction. As a peptide, MTD fused with octa-arginine (R8), a CPP, induces necrosis related to intracellular calcium influx and destruction of mitochondria and endoplasmic reticulum. We searched for homologs of MTD, and compared their cell killing capability when fused with R8. Three of the seven peptides triggered cell death with similar mechanisms. The comparative analysis of peptide sequences showed that four amino acid sites of MTD are critical in regulating necrosis, suggesting the potential to generate artificial, adjustable cytotoxic peptides, which could be effective medicines for many diseases. Thus, homologs functionality could hint to the functions of their belonging proteins.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.31-40
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• 2021

All living beings on earth have an important mechanism of 24-h periodicity, which controls their physiology, metabolism, and behavior. In humans, 24-h periodicity is regulated by the superchiasmatic nucleus (SCN) through external and environmental cues. Peripheral organs demonstrate circadian rhythms and circadian clock functions, and these are also observed in cultured cell lines. Every cell contains a CLOCK: BMAL1 loop for the generation of circadian rhythms. In this review, we focused on cell autonomous circadian rhythms in immune cells, the inflammatory diseases caused by disruption of circadian rhythms in hormones, and the role of clock genes in inflammatory diseases.

• IMMUNE NETWORK
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• 제3권3호
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• pp.176-181
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• 2003

Background: The molecular basis of follicular dendritic cells (FDC)-germinal center (GC) B cell interaction is largely unknown, although this cellular interaction is thought to be important for the whole process of GC B cell differentiation. Methods: Using FDC-like cells, HK, and highly purified GC B cells, we attempted to identify the molecules that play critical roles in the interactions between FDC and B cells. GC B cells were co-cultured with HK cells and soluble CD154 in the presence or absence of various function-blocking monoclonal antibodies to examine their effect on GC B cell binding to HK cells and B cell proliferation. Results: Anti-CD11a and anti-CD54 antibodies inhibited GC B cell binding to HK cells while anti-CD49d and anti-CD106 antibodies did not. GC B cell proliferation was not impaired by the disruption of GC B cell-HK cell adherence. Conclusion: Our results suggest that CD11a/CD18-CD54 interactions play an important roles in the initial binding of GC B cells to FDC and diffusible growth factors from FDC may be responsible the massive proliferation of GC B cells.

• 대한수의학회지
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• 제49권4호
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• pp.279-284
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• 2009

This research aimed to investigate the time-course effect of epichlorohydrin (ECH) on epididymal histopathology in Sprague-Dawley rats. Twenty-four male rats were randomly assigned to four groups with 6 rats in each group and were administered a single oral dose of ECH (70 mg/kg) or its vehicle. Six animals each were sacrificed on days 0 (control), 1, 2, and 7 after treatment. During the study period, clinical signs, body weights, reproductive organ weights, testicular spermatid count, epididymal sperm count, motility and morphology, and histopathology were examined. No treatmentrelated effects on body weights and reproductive organ weights were noted at any time point. On the contrary, sperm motility decreased slightly on days 1 and 2 after treatment and then decreased significantly on day 7 after treatment. The first signs of histological changes were the appearance of cell debris in the ducts and vacuolization of the epithelial cells observed in the proximal caput epididymis on day 1 after treatment. The incidences and grades of the histological changes including cell debris in the ducts, epithelial vacuolization, oligospermia, and epithelial disruption increased on day 2 and then decreased slightly on day 7 after treatment. These results show that a single oral dose of 70 mg/kg ECH to male rats results in cell debris in the ducts and vacuolization of the epithelial cells in the proximal caput epididymis, followed by reversible oligospermia, epithelial disruption, and decreased sperm motility.

• 한국정보과학회논문지:정보통신
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• 제31권2호
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• pp.146-157
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• 2004

이동 사용자에게 지속적인 서비스품질 보장을 제공하기 위해서는 일반적으로 사용자 방문할 것으로 예상되는 지역에 사전에 중복적으로 자원을 예약하는 방안을 사용한다. 이와 같은 방식에서 관건이 되는 문제는 중복적 자원 예약에 의한 자원 낭비를 줄이면서도 서비스품질 보장의 연속성을 유지하는 것이다. 본 논문에서는 지리적으로 인접한 두 개의 무선 네트워크 도메인 사이에 두 도메인에 모두 속하는 그레이 셀을 두는 무선 네트워크 구조를 제안하고, 이를 이용하여 무선 네트워크에서의 중복적인 자원 예약을 완전히 제거하면서도 도메인 간 이동으로 인한 일시적 자원 예약 단절을 크게 줄일 수 있는 방안을 제안하였다. 시뮬레이션을 통하여 제안한 방안은 도메인 간 이동이 발생하는 경우에도 도메인 내에서 이동 할 때와 유사한 성능을 보이며, 예약 단절 시간이나 패킷 손실율면에서 기존의 방법보다 훨씬 나은 성능을 제공함을 볼 수 있었다.

• Toxicological Research
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• 제11권1호
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• pp.1-8
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• 1995

Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(\leq 35 {\mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {\mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$\mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {\mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435\pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333\pm11$$pmoles/{10^6}$ cells in cells exposed to $35{\mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{\mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{\mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.

• BMB Reports
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• 제53권8호
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• pp.393-399
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• 2020

Recent advancements in the resolution and throughput of single-cell analyses, including single-cell RNA sequencing (scRNA-seq), have achieved significant progress in biomedical research in the last decade. These techniques have been used to understand cellular heterogeneity by identifying many rare and novel cell types and characterizing subpopulations of cells that make up organs and tissues. Analysis across various datasets can elucidate temporal patterning in gene expression and developmental cues and is also employed to examine the response of cells to acute injury, damage, or disruption. Specifically, scRNA-seq and spatially resolved transcriptomics have been used to describe the identity of novel or rare cell subpopulations and transcriptional variations that are related to normal and pathological conditions in mammalian models and human tissues. These applications have critically contributed to advance basic cardiovascular research in the past decade by identifying novel cell types implicated in development and disease. In this review, we describe current scRNA-seq technologies and how current scRNA-seq and spatial transcriptomic (ST) techniques have advanced our understanding of cardiovascular development and disease.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.759-769
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• 2002

Mutated forms of ras are found in many human tumors and the rate of incidence is significantly higher in colon and pancreatic cancers. The protein product from the ras oncogene is a small G-protein, $p21^{ras}{\;}(Ras)$ that is known to playa key role in the signal transduction cascade and cell differentiation and proliferation. Mutated Ras is unable to regulate itself and remains constantly activated, leading to uncontrolled cell growth. The function of Ras in signal transduction requires its location near the growth factor receptor at the cell membrane. However, Ras does not have a transmembrane domain. Ras requires farnesylation to increase its hydrophobicity and subsequent plasma membrane association for its transforming activity. This key post-translational modification is catalyzed by the enzyme Ras farnesyltransferase (FTase), which transfers a farnesyl group from farnesylpyrophosphate to the C-terminal cysteine of the Ras protein. The requirement has focused attention on FTase as a target for therapeutic intervention. Selective inhibition of FTase will prevent Ras protein from association with the plasma membrane, leading to a disruption of oncogenic Ras function.