• Title/Summary/Keyword: real-time mechanism

Search Result 1,052, Processing Time 0.034 seconds

Amelioration of DSS-induced colitis in mice by TNF-α-stimulated mesenchymal stem cells derived from feline adipose tissue via COX-2/PGE2 activation

  • Kyeongbo Kim;Ju-Hyun An;Su-Min Park;GaHyun Lim;Kyung-Won Seo;Hwa-Young Youn
    • Journal of Veterinary Science
    • /
    • v.24 no.4
    • /
    • pp.52.1-52.13
    • /
    • 2023
  • Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b+CD206+ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.

RNA-Seq explores the functional role of the fibroblast growth factor 10 gene in bovine adipocytes differentiation

  • Nurgulsim Kaster;Rajwali Khan;Ijaz Ahmad;Kazhgaliyev Nurlybay Zhigerbayevich;Imbay Seisembay;Akhmetbekov Nurbolat;Shaikenova Kymbat Hamitovna;Omarova Karlygash Mirambekovna;Makhanbetova Aizhan Bekbolatovna;Tlegen Garipovich Amangaliyev;Ateikhan Bolatbek;Titanov Zhanat Yeginbaevich;Shakoor Ahmad;Zan Linsen;Begenova Ainagul Baibolsynovna
    • Animal Bioscience
    • /
    • v.37 no.5
    • /
    • pp.929-943
    • /
    • 2024
  • Objective: The present study was executed to explore the molecular mechanism of fibroblast growth factor 10 (FGF10) gene in bovine adipogenesis. Methods: The bovine FGF10 gene was overexpressed through Ad-FGF10 or inhibited through siFGF10 and their negative control (NC) in bovine adipocytes, and the multiplicity of infection, transfection efficiency, interference efficiency were evaluated through quantitative real-time polymerase chain reaction, western blotting and fluorescence microscopy. The lipid droplets, triglycerides (TG) content and the expression levels of adipogenic marker genes were measured during preadipocytes differentiation. The differentially expressed genes were explored through deep RNA sequencing. Results: The highest mRNA level was found in omasum, subcutaneous fat, and intramuscular fat. Moreover, the highest mRNA level was found in adipocytes at day 4 of differentiation. The results of red-oil o staining showed that overexpression (Ad-FGF10) of the FGF10 gene significantly (p<0.05) reduced the lipid droplets and TG content, and their down-regulation (siFGF10) increased the measurement of lipid droplets and TG in differentiated bovine adipocytes. Furthermore, the overexpression of the FGF10 gene down regulated the mRNA levels of adipogenic marker genes such as CCAAT enhancer binding protein alpha (C/EBPα), fatty acid binding protein (FABP4), peroxisome proliferator-activated receptor-γ (PPARγ), lipoprotein lipase (LPL), and Fas cell surface death receptor (FAS), similarly, down-regulation of the FGF10 gene enriched the mRNA levels of C/EBPα, PPARγ, FABP4, and LPL genes (p<0.01). Additionally, the protein levels of PPARγ and FABP4 were reduced (p<0.05) in adipocytes infected with Ad-FGF10 gene and enriched in adipocytes transfected with siFGF10. Moreover, a total of 1,774 differentially expressed genes (DEGs) including 157 up regulated and 1,617 down regulated genes were explored in adipocytes infected with Ad-FGF10 or Ad-NC through deep RNA-sequencing. The top Kyoto encyclopedia of genes and genomes pathways regulated through DEGs were the PPAR signaling pathway, cell cycle, base excision repair, DNA replication, apoptosis, and regulation of lipolysis in adipocytes. Conclusion: Therefore, we can conclude that the FGF10 gene is a negative regulator of bovine adipogenesis and could be used as a candidate gene in marker-assisted selection.

Bta-miR-365-3p-targeted FK506-binding protein 5 participates in the AMPK/mTOR signaling pathway in the regulation of preadipocyte differentiation in cattle

  • Mengdi Chen;Congcong Zhang;Zewen Wu;Siwei Guo;Wenfa Lv;Jixuan Song;Beibei Hao;Jinhui Bai;Xinxin Zhang;Hongyan Xu;Guangjun Xia
    • Animal Bioscience
    • /
    • v.37 no.7
    • /
    • pp.1156-1167
    • /
    • 2024
  • Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3' untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Wedelolactone Promotes the Chondrogenic Differentiation of Mesenchymal Stem Cells by Suppressing EZH2

  • Wei Qin;Lin Yang;Xiaotong Chen;Shanyu Ye;Aijun Liu;Dongfeng Chen;Kunhua Hu
    • International Journal of Stem Cells
    • /
    • v.16 no.3
    • /
    • pp.326-341
    • /
    • 2023
  • Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods and Results: Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3'-untranscribed region. Conclusions: These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

Identification and functional prediction of long non-coding RNAs related to oxidative stress in the jejunum of piglets

  • Jinbao Li;Jianmin Zhang;Xinlin Jin;Shiyin Li;Yingbin Du;Yongqing Zeng;Jin Wang;Wei Chen
    • Animal Bioscience
    • /
    • v.37 no.2
    • /
    • pp.193-202
    • /
    • 2024
  • Objective: Oxidative stress (OS) is a pathological process arising from the excessive production of free radicals in the body. It has the potential to alter animal gene expression and cause damage to the jejunum. However, there have been few reports of changes in the expression of long noncoding RNAs (lncRNAs) in the jejunum in piglets under OS. The purpose of this research was to examine how lncRNAs in piglet jejunum change under OS. Methods: The abdominal cavities of piglets were injected with diquat (DQ) to produce OS. Raw reads were downloaded from the SRA database. RNA-seq was utilized to study the expression of lncRNAs in piglets under OS. Additionally, six randomly selected lncRNAs were verified using quantitative real-time polymerase chain reaction (qRT-PCR) to examine the mechanism of oxidative damage. Results: A total of 79 lncRNAs were differentially expressed (DE) in the treatment group compared to the negative control group. The target genes of DE lncRNAs were enriched in gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways. Chemical carcinogenesis-reactive oxygen species, the Foxo signaling pathway, colorectal cancer, and the AMPK signaling pathway were all linked to OS. Conclusion: Our results demonstrated that DQ-induced OS causes differential expression of lncRNAs, laying the groundwork for future research into the processes involved in the jejunum's response to OS.

Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines

  • Jisu Kim;Shuya Zhang ;Ying Zhu;Ruirui Wang;Jianxin Wang
    • Journal of Ginseng Research
    • /
    • v.47 no.5
    • /
    • pp.627-637
    • /
    • 2023
  • Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

Differential expression of tescalcin by modification of promoter methylation controls cell survival in gastric cancer cells

  • Tae Woo Kim;Seung Ro Han;Jong-Tae Kim;Seung-Min Yoo;Myung-Shin Lee;Seung-Hoon Lee;Yun Hee Kang;Hee Gu Lee
    • Oncology Letters
    • /
    • v.41 no.6
    • /
    • pp.3464-3474
    • /
    • 2019
  • The EF-hand calcium binding protein tescalcin (TESC) is highly expressed in various human and mouse cancer tissues and is therefore considered a potential oncogene. However, the underlying mechanism that governs TESC expression remains unclear. Emerging evidence suggests that TESC expression is under epigenetic regulation. In the present study, the relationship between the epigenetic modification and gene expression of TESC in gastric cancer was investigated. To evaluate the relationship between the methylation and expression of TESC in gastric cancer, the methylation status of CpG sites in the TESC promoter was analyzed using microarray with the Illumina Human Methylation27 BeadChip (HumanMethylation27_270596_v.1.2), gene profiles from the NCBI Dataset that revealed demethylated status were acquired, and real-time methylation-specific PCR (MSP) in gastric cancer cells was conducted. In the present study, it was demonstrated that the hypermethylation of TESC led to the downregulation of TESC mRNA/protein expression. In addition, 5-aza-2c-deoxycytidine (5'-aza-dC) restored TESC expression in the tested gastric cancer cells except for SNU-620 cells. ChIP assay further revealed that the methylation of the TESC promoter was associated with methyl-CpG binding domain protein (MBD)1, histone deacetylase (HDAC)2, and Oct-1 and that treatment with 5'-aza-dC facilitated the dissociation of MBD1, HDAC2, and Oct-1 from the promoter of TESC. Moreover, silencing of TESC increased MBD1 expression and decreased the H3K4me2/3 level, thereby causing transcriptional repression and suppression of cell survival in NCI-N87 cells; conversely, overexpression of TESC downregulated MBD1 expression and upregulated the H3K4me2 level associated with active transcription in SNU-638 cells. These results indicated that the differential expression of TESC via the modification status of the promoter and histone methylation controled cell survival in gastric cancer cells. Overall, the present study provided a novel therapeutic strategy for gastric cancer.

Potential of River Bottom and Bank Erosion for River Restoration after Dam Slit in the Mountain Stream

  • Kang, Ji-Hyun;So, Kazama
    • Proceedings of the Korea Water Resources Association Conference
    • /
    • 2011.05a
    • /
    • pp.46-46
    • /
    • 2011
  • Severe sediment erosion during floods occur disaster and economic losses, but general sediment erosion is basic mechanism to move sediment from upstream to downstream river. In addition, it is important process to change river form. Check dam, which is constructed in mountain stream, play a vital role such as control of sudden debris flow, but it has negative aspects to river ecosystem. Now a day, check dam of open type is an alternative plan to recover river biological diversity and ecosystem through sediment transport while maintaining the function of disaster control. The purpose of this paper is to verify sediment erosion progress of river bottom and bank as first step for river restoration after dam slit by cross-sectional shear stress and critical shear stress. Study area is upstream reach of slit check dam in mountain stream, named Wasada, in Japan. The check dam was slit with two passages in August, 2010. The transects were surveyed for four upstream cross-sections, 7.4 m, 34 m, 86 m, and 150 m distance from dam in October 2010. Sediment size was surveyed at river bottom and bank. Sediment of cobble size was found at the wetted bottom, and small size particles of sand to medium gravel composed river bank. Discharge was $2.5\;m^3/s$ and bottom slope was 0.027 m/m. Excess shear stress (${\tau}_{ex}$) was calculated for hydraulic erosion by subtracting the values of critical shear stress (${\tau}_{c}$) from the value of shear stress (${\tau}$) at river bottom and bank (${\tau}_{ex}=\tau-{\tau}_c$). Shear stress of river bottom (${\tau}_{bottom}$) was calculated using the cross-sectional shear stress, and bank shear stress (${\tau}_{bank}$) was calculated from the method of Flintham and Carling (1988). $${\tau}_{bank}={\tau}^*SF_{bank}((B+P_{bed})/(2^*P_{bank}))$$ where $SF_{bank}=1.77(P_{bed}/p_{bank}+1.5)^{-1.4}$, B is the water surface width, $P_{bed}$ and $P_{bank}$ are wetted parameter of the bed and bank. Estimated values for ${\tau}_{bottom}$ for a flow of $2.5\;m^3/s$ were lower as 25.0 (7.5 m cross-section), 25.7 (34 m), 21.3 (86 m) and 19.8 (150 m), in N/$m^2$, than critical shear stress (${\tau}_c=62.1\;N/m^2$) with cobble of 64 mm. The values were insufficient to erode cobble sediment. In contrast, even if the values of ${\tau}_{bank}$ were lower than the values for ${\tau}_{bottom}$ as 18.7 (7.5 m), 19.3 (34 m), 16.1 (86 m) and 14.7 (150 m), in N/$m^2$, excess shear stresses were calculated at the three cross-sections of 7.5 m, 34 m, and 86 m distances compare with ${\tau}_c$ is 15.5 N/$m^2$ of 16mm gravel. Bank shear stresses were sufficient for erosion of the medium gravel to sand. Therefore there is potential to erode lateral bank than downward erosion in a flow of $2.5\;m^3/s$. Undercutting of the wetted bank can causes bank scour or collapse, therefore this channel has potential to become wider at the same time. This research is about a potential of sediment erosion, and the result could not verify with real data. Therefore it need next step for verification. In addition an erosion mechanism for river restoration is not simple because discharge distribution is variable by snow-melting or rainy season, and a function for disaster control will recover by big precipitation event. Therefore it needs to consider the relationship between continuous discharge change and sediment erosion.

  • PDF

A Study on the Gene Expression of Adipogenic Regulators by an Herbal Composition (생약복합물에 의한 지방세포형성 조절자의 유전자 발현 연구)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Bae, Sung-Min;Chae, Soo-Ahn;Lee, Jung-Ju;Oh, Dong-Jin;Park, Suk-Won;Cho, Soo-Hyun;Shim, Yae-Jie;Yoon, Yoo-Sik
    • Journal of Life Science
    • /
    • v.20 no.5
    • /
    • pp.729-735
    • /
    • 2010
  • In our previous study, it was reported that an herbal mixture, SH21B, inhibits fat accumulation and adipogenesis both in vitro and in vivo models of obesity. SH21B is a mixture composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd, and Nelumbo nucifera Gaertner (Ratio 3:3:3:3:3:2:2). The aim of this study was to investigate the detailed molecular mechanisms of the effects of SH21B on various regulators of the adipogenesis pathway. During the adipogenesis of 3T3-L1 cells, SH21B significantly decreased the expression levels of central transcription factors of adipogenesis, such as peroxisome proliferator-activated receptor (PPAR)$\gamma$ and CCAAT/enhancer binding protein (C/EBP)$\alpha$. To elucidate the detailed molecular mechanism of the anti-adipogenic effects of SH21B, we examined the expression levels of the various pro-adipogenic or anti-adipogenic regulators of adipogenesis upstream of $PPAR{\gamma}$ and C/$EBP{\alpha}$. The mRNA levels of Krox20 and Kruppel-like factor (KLF) 15, which are pro-adipogenic regulators, were significantly down-regulated by SH21B treatment, whereas the mRNA levels of C/$EBP{\gamma}$ and KLF5 were not changed. KLF2 and C/EBP homologous protein (CHOP), which are anti-adipogenic regulators, were significantly up-regulated by SH21B treatment. These results suggest that the molecular mechanism of the anti-adipogenic effect of SH21B involves both the down-regulations of pro-adipogenic regulators, such as Krox20 and KLF15, and the up-regulations of anti-adipogenic regulators, such as KLF2 and CHOP, which results in the suppression of central transcription factors of adipogenesis including $PPAR{\gamma}$ and C/$EBP{\alpha}$.

A Study on Design of Agent based Nursing Records System in Attending System (에이전트기반 개방병원 간호기록시스템 설계에 관한 연구)

  • Kim, Kyoung-Hwan
    • Journal of Intelligence and Information Systems
    • /
    • v.16 no.2
    • /
    • pp.73-94
    • /
    • 2010
  • The attending system is a medical system that allows doctors in clinics to use the extra equipment in hospitals-beds, laboratory, operating room, etc-for their patient's care under a contract between the doctors and hospitals. Therefore, the system is very beneficial in terms of the efficiency of the usage of medical resources. However, it is necessary to develop a strong support system to strengthen its weaknesses and supplement its merits. If doctors use hospital beds under the attending system of hospitals, they would be able to check a patient's condition often and provide them with nursing care services. However, the current attending system lacks delivery and assistance support. Thus, for the successful performance of the attending system, a networking system should be developed to facilitate communication between the doctors and nurses. In particular, the nursing records in the attending system could help doctors monitor the patient's condition and provision of nursing care services. A nursing record is the formal documentation associated with nursing care. It is merely a data repository that helps nurses to track their activities; nursing records thus represent a resource of primary information that can be reused. In order to maximize their usefulness, nursing records have been introduced as part of computerized patient records. However, nursing records are internal data that are not disclosed by hospitals. Moreover, the lack of standardization of the record list makes it difficult to share nursing records. Under the attending system, nurses would want to minimize the amount of effort they have to put in for the maintenance of additional records. Hence, they would try to maintain the current level of nursing records in the form of record lists and record attributes, while doctors would require more detailed and real-time information about their patients in order to monitor their condition. Therefore, this study developed a system for assisting in the maintenance and sharing of the nursing records under the attending system. In contrast to previous research on the functionality of computer-based nursing records, we have emphasized the practical usefulness of nursing records from the viewpoint of the actual implementation of the attending system. We suggested that nurses could design a nursing record dictionary for their convenience, and that doctors and nurses could confirm the definitions that they looked up in the dictionary through negotiations with intelligent agents. Such an agent-based system could facilitate networking among medical institutes. Multi-agent systems are a widely accepted paradigm for the distribution and sharing of computation workloads in the scientific community. Agent-based systems have been developed with differences in functional cooperation, coordination, and negotiation. To increase such communication, a framework for a multi-agent based system is proposed in this study. The agent-based approach is useful for developing a system that promotes trade-offs between transactions involving multiple attributes. A brief summary of our contributions follows. First, we propose an efficient and accurate utility representation and acquisition mechanism based on a preference scale while minimizing user interactions with the agent. Trade-offs between various transaction attributes can also be easily computed. Second, by providing a multi-attribute negotiation framework based on the attribute utility evaluation mechanism, we allow both the doctors in charge and nurses to negotiate over various transaction attributes in the nursing record lists that are defined by the latter. Third, we have designed the architecture of the nursing record management server and a system of agents that provides support to the doctors and nurses with regard to the framework and mechanisms proposed above. A formal protocol has also been developed to create and control the communication required for negotiations. We verified the realization of the system by developing a web-based prototype. The system was implemented using ASP and IIS5.1.