• Journal of Microbiology and Biotechnology
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• 제12권5호
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• pp.735-739
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• 2002

Large quantities of porcine hepatocyte aggregates with various degrees of aggregation (DA) could be obtained by controlling the suspension periods (0,9,24, and 48 h), and by entrapping the hepatocyte aggregates in model materials of encapsulation such as Ca-alginate and type-I collagen gels. The effects of DA on liver-specific functions of hepatocytes were evaluated in order to obtain optimum DA for the cell source of bioartificial liver (BAL) systems. Irregular rugged aggregates (size $75 \pm 28$ $\mu\textrm{m}$) farmed by 24 h of suspension culturing showed peak viability and hepatic functions such as ammonia removal and albumin secretion in the two types of entrapment systems, thus offering themselves as a stable cell source of a BAL system for hepatic functions and scale-up.

• Nutrition Research and Practice
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• 제14권6호
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• pp.580-592
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• 2020

BACKGROUND/OBJECTIVES: The present study aimed to further investigate the potential health beneficial effects of long-term seaweed supplementation on lipid metabolism and hepatic functions in DIO mice. MATERIALS/METHODS: Four brown seaweeds (Undaria pinnatifida [UP], Laminaria japonica [LJ], Sargassum fulvellum [SF], or Hizikia fusiforme [HF]) were added to a high fat diet (HFD) at a 5% ratio and supplemented to C57BL/6N mice for 16 weeks. Triglycerides (TGs) and total cholesterol (TC) in the liver, feces, and plasma were measured. Fecal bile acid (BA) levels in feces were monitored. Hepatic insulin signaling- and lipogenesis-related proteins were evaluated by Western blot analysis. RESULTS: Fasting blood glucose levels were significantly reduced in the LJ, SF, and HF groups compared to the HFD group by the end of 16-week feeding period. Plasma TG levels and hepatic lipid accumulation were significantly reduced in all 4 seaweed supplemented groups, whereas plasma TC levels were only suppressed in the UP and HF groups compared to the HFD group. Fecal BA levels were significantly elevated by UP, LJ, and SF supplementation compared to HFD feeding only. Lastly, regarding hepatic insulin signaling-related proteins, phosphorylation of 5'-AMP-activated protein kinase was significantly up-regulated by all 4 types of seaweed, whereas phosphorylation of protein kinase B was up-regulated only in the SF and HF groups. Lipogenesis-related proteins in the liver were effectively down-regulated by HF supplementation in DIO mice. CONCLUSIONS: Brown seaweed consumption showed hypotriglyceridemic effects in the prolonged DIO mouse model. Specifically, combinatory regulation of BA excretion and lipogenesis-related proteins in the liver by seaweed supplementation contributed to the reduction of plasma and hepatic TG levels, which inhibited hyperglycemia in DIO mice. Thus, the discrepant and species-specific functions of brown seaweeds provide novel insights for the selection of future targets for therapeutic agents.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XIII)
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• pp.305-306
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• 2003

To treat fulminant hepatic failure (FHF) patients, various extracorporeal bioartificial liver (BAL) systems have been developed. Several requirements should be met for the development of BAL systems: hepatocytes should be cultured in a sufficiently high density; their metabolic functions should be of a sufficiently high level and duration; and the BAL systems module should permit scaling-up and aseptic handling. Several investigators have found that freshly isolated primary hepatocytes can be cultured into three dimensional, tightly packed, freely suspended, multicellular aggregates, or spheroids. These specialized cell structures exhibited enhanced liver specific functions and a prolonged differentiated state compared to cells maintained in a monolayer culture. Cells in spheroids appear to mimic the morphology and ultrastructure of the in vivo liver lobule. The ability of hepatocytes to organize into three-dimensional structures was hypothesized to contribute to their enhanced liver-specific activities. In this study, the ammonia removal rate and urea secretion rate of pig hepatocytes spheroids encapsulated in Ca-alginate bead were determined. A packed-bed bioreactor with encapsulated pig hepatocytes was devised as BAL support system. The efficacy of the system was evaluated in vitro.

• 폴리머
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• 제32권2호
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• pp.131-137
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• 2008

전기방사법에 의해 폴리스테렌 나노섬유 부직포를 제조하였고, 간세포의 접착을 유도하기 위해 간세포접착 리간드인 Poly[N-p-vinylbenzyl-O-$\beta$-D-galactopyranocyl-($1{\rightarrow}4$)-D-gluconamide](PVLA)를 나노섬유의 표면에 코팅하였다. 얻어진 나노섬유는 평균직경이 500 nm이었고 분광학적인 방법을 통해 PS 나노섬유 표면의 개질 여부를 확인하였다. 장기간 배양시의 간세포 생존율을 MTT법으로 조사한 결과 기존의 세포배양접시에서는 급격하게 세포생존율이 감소함에 비해 PVLA가 코팅된 나노섬유상에서는 생존율이 서서히 감소하였으며 약 3주간에 걸쳐 간세포가 생존율이 유지되었다. 간세포의 대표적인 기능인 알부민분비 및 요소분해능을 측정한 결과 기존의 세포배양접시에서는 급격하게 간세포기능이 저하되었지만, PVLA가 코팅된 나노섬유상에서는 약 3주정도 초기의 간세포기능을 유지하는 것이 밝혀졌다.

• 한국식품위생안전성학회:학술대회논문집
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• 한국식품위생안전성학회 2002년도 춘계학술발표대회 및 심포지움
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• pp.147-147
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• 2002

This experimental study was carried out to investigate on the safety of Nog-yong aqua-acupuncture solution in primary culture of adult rat hepatocytes. Primary culture of adult rat hepatocytes has been considered as a ideal model for toxicological studies because cultured hepatocytes maintained many liver-specific functions. In this research, we investigated the effects of Nog-yong aqua-aqupunture(1-10$\mu\textrm{g}$/ml) on cytotoxicites in primary culture of adult rat hepatocytes using LDH release assays. Hepatic glutathione level. glutathione-S-transferase activity, and albumin synthesis were not affected by treatment with Nog-yong aqua-aqupuntur alone. Nog-yong aqua-aqupuncoure solution(0.5-$10{\mu}\textrm{g}$/ml) on cytotoxicites in primary culture of adult rat hepatocytes using LDH release not significantly affected normal functional charaterists.

• BMB Reports
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• 제40권1호
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• pp.130-134
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• 2007

Haptoglobin (Hp) is a glycoprotein that is produced by hepatic cells and secreted into the circulation. While studying the physiologic functions of Hp, we found that Hp synthesized in THP-1 monocytic cells was largely retained within cells, although Hp is considered a secretory protein. To investigate the molecular mechanism on Hp secretion in THP-1 cells, in the present study, we examined the effect of protein kinase C (PKC) on Hp secretion. When several inhibitors of PKC isoforms were tested, only Rottlerin, a specific inhibitor of PKC-$\delta$, completely blocked Hp secretion from cells to culture medium. To confirm the role of PKC-$\delta$ in Hp secretion, Hp-overexpressing COS7 cells were transiently transfected with a wild-type or a dominantnegative mutant of the PKC-$\delta$ gene. Mutant PKC-$\delta$ significantly inhibited Hp secretion, whereas the wild-type gene slightly increased Hp secretion. These results demonstrate that the PKC-$\delta$ signal is involved in Hp secretion.

• 대한약침학회지
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• 제20권4호
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.

• Molecules and Cells
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• 제46권9호
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• pp.527-534
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• 2023

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

• 생명과학회지
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• 제31권8호
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• pp.710-718
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• 2021

태반유래 중간엽줄기세포(PD-MSCs)는 재생의학에서 세포기반치료제로 잘 알려진 세포군이다. PD-MSCs의 손상된 부위로의 이동과 호밍 기능은 MSC 생착의 중요한 특성이다. miRNA는 최근 MSC의 증식, 생존 이동과 같은 중요한 기능을 조절하는 것으로 알려져 있다. 본 연구의 목적은 담관결찰(BDL) 쥐 모델에서 PD-MSCs 호밍에 관련된 miRNA 및 표적 유전자를 동정하는 것으로, 마이크로어레이 분석을 이용하여 PD-MSCs 호밍에 관여하는 유전자 표적 miRNA를 선별하였다. BDL 쥐모델에 PD-MSCs을 이식한 일주일 후 간 조직에서 PD-MSCs 생착여 부는 면역형광분석법과 qRT-PCR에 의한 인간 Alu유전자 발현으로 확인되었다. 저산소 및 정상조건(Hyp/Nor)에서 이동한 PD-MSC에 비하여, PD-MSCs 이식한 BDL군 간 조직에서 miRNAs 발현의 차이가 크게 나타났으며, PD-MSCs 호밍 관련 miRNA와 표적유전자를 검증하였다. miR199a-5p 및 miR-148a-3p에 대한 표적 유전자 인테그린 α4 (ITGA4)와 α5 (ITGA5)의 발현은 이식(Tx)그룹에서(p<0.05) 유의하게 상향 조절되었다. 또한 인테그린 β1 (ITGB1)과 β8 (ITGB8)의 발현은 miR-183-5p 및 miR-145-5p억제에 의하여 크게 증가되었다. 따라서 이러한 결과는 BDL에 의해 손상된 쥐간에서 PD-MSCs가 호밍효과을 위해 인테그린 그룹과 관련된 miRNA 발현 조절에 관여함을 나타내었다. 본 연구결과는 miRNA에 의한 인테그린 그룹 조절기능이 BDL에 의해 유도된 간섬유증 쥐모델에서 PD-MSCs의 치료효과에 기여할 수 있음을 시사한다.