• Title/Summary/Keyword: biomedical

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Nebulin C-terminus Interacts with NCBP51, a New Isoform of RING Finger Protein 125 (RNF125)

  • Kim, Ji-Hee;Kim, Hyun-Suk;Park, Eun-Ran;Choi, Jae-Kyoung;Lee, Yeong-Mi;Choi, Jun-Hyuk;Shin, Jung-Woog;Kim, Chong-Rak
    • Biomedical Science Letters
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    • v.13 no.1
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    • pp.1-10
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    • 2007
  • Nebulin, a giant modular protein from muscle, is thought to act as molecular ruler in sarcomere assembly. In skeletal muscle, the C-terminal ${\sim}50 kDa$ region of nebulin extends into the Z-line lattice. The most recent studies implicated highlighting its extensive isoform diversity and exciting reports revealed its expression in cardiac and non-muscle tissues containing brain. Also these novel findings are indicating that nebulin is actually a multifunctional filament system, perhaps playing roles in signal transduction, contractile regulation, and myofibril force generation, as well as other not yet defined functions. However the binding protein of nebulin and function in brain is still unknown. A novel binding partner of nebulin C-terminal region was identified by screening a human brain cDNA library using yeast two-hybrid system. Nebulin C-terminus binding protein 51 (NCBP51) was contained a RING-finger domain and identified a new isoform of RING finger protein 125 (RNF125). The interaction was confirmed using the GST pull-down assay. NCBP51 belongs to a family of the RING finger proteins and its function remains to be identified in brain. The role of nebulin and NCBP51 will be studied by loss-of-function using siRNA technique in brain.

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Effect of chloroform extract of traditional Dicranopteris linearis leaves against paracetamol- and CCl4-induced liver toxicity in rats

  • Din, Syafawati Shamsahal;Mamat, Siti Syariah;Ismail, Noor Aisyah;Zainulddin, Wan Noraziemah Wan;Zabidi, Zalina;Yahya, Farhana;Kamisan, Farah Hidayah;Mohtarrudin, Norhafizah;Othman, Fezah;Suhaili, Zarizal;Zakaria, Zainul Amiruddin
    • CELLMED
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    • v.2 no.4
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    • pp.34.1-34.5
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    • 2012
  • The present study aimed to determine the hepatoprotective activity of the chloroform extract of D. linearis leaves (CEDL) using the paracetamol (PCM)- and carbon tetrachloride ($CCl_4$)-induced liver injury models in rats. The rats received $dH_2O$ (negative control), 200 mg/kg of silymarin (positive control) or CEDL (50, 250 and 500 mg/kg) orally once daily for 7 days and then were subjected to the hepatotoxic induction on the $7^{th}$ day. The samples (i.e. blood and liver) were collected and underwent biochemical and microscopical analysis, respectively. From the data obtained, both inducers caused significant (p < 0.05) increase in the levels of AST and ALT when compared to the control group, which were significantly (p < 0.05) reduced by CEDL in a generally dose-dependent manner. These biochemical findings were supported by the histopathological analysis and histological scoring. In conclusion, CEDL possesses potential hepatoprotective activity, which could be associated with its flavonoid and tannin contents with the mechanisms of hepatoprotection linked to either its antioxidant or anti-inflammtory/immunomodulating activities. Further in-depth studies are required to identify the responsible bioactive compound.

In vitro Expansion of Umbilical Cord Blood Derived Mesenchymal Stem Cells (UCB-MSCs) Under Hypoxic Conditions

  • Yang, Jungyun;Kwon, Jihye;Kim, Miyeon;Bae, Yunkyung;Jin, Hyejin;Park, Hohyun;Eom, Young Woo;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.21 no.1
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    • pp.40-49
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    • 2015
  • Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multi-lineage cells, thus highlighting the feasibility of using umbilical cord blood-derived MSCs (UCB-MSCs) for cell-therapy and tissueengineering. However, the low numbers of UCB-MSC derived from clinical samples requires that an ex vivo expansion step be implemented. As most stem cells reside in low oxygen tension environments (i.e., hypoxia), we cultured the UCBMSCs under 3% $O_2$ or 21% $O_2$ and the following parameters were examined: proliferation, senescence, differentiation and stem cell specific gene expression. UCB-MSCs cultured under hypoxic conditions expanded to significantly higher levels and showed less senescence compared to UCB-MSCs cultured under normoxic conditions. In regards to differentiation potential, UCB-MSCs cultured under hypoxic and normoxic conditions both underwent similar levels of osteogenesis as determined by ALP and von Kossa assay. Furthermore, UCB-MSCs cultured under hypoxic conditions exhibited higher expression of OCT4, NANOG and SOX2 genes. Moreover, cells expanded under hypoxia maintained a stem cell immnunophenotype as determined by flow cytometry. These results demonstrate that the expansion of human UCB-MSCs under a low oxygen tension microenvironment significantly improved cell proliferation and differentiation. These results demonstrate that hypoxic culture can be rapidly and easily implemented into the clinical-scale expansion process in order to maximize UCB-MSCs yield for application in clinical settings and at the same time reduce culture time while maintaining cell product quality.

CDISC Transformer: a metadata-based transformation tool for clinical trial and research data into CDISC standards

  • Park, Yu-Rang;Kim, Hye-Hyeon;Seo, Hwa-Jeong;Kim, Ju-Han
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.5 no.10
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    • pp.1830-1840
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    • 2011
  • CDISC (Clinical Data Interchanging Standards Consortium) standards are to support the acquisition, exchange, submission and archival of clinical trial and research data. SDTM (Study Data Tabulation Model) for Case Report Forms (CRFs) was recommended for U.S. Food and Drug Administration (FDA) regulatory submissions since 2004. Although the SDTM Implementation Guide gives a standardized and predefined collection of submission metadata 'domains' containing extensive variable collections, transforming CRFs to SDTM files for FDA submission is still a very hard and time-consuming task. For addressing this issue, we developed metadata based SDTM mapping rules. Using these mapping rules, we also developed a semi-automatic tool, named CDISC Transformer, for transforming clinical trial data to CDISC standard compliant data. The performance of CDISC Transformer with or without MDR support was evaluated using CDISC blank CRF as the 'gold standard'. Both MDR and user inquiry-supported transformation substantially improved the accuracy of our transformation rules. CDISC Transformer will greatly reduce the workloads and enhance standardized data entry and integration for clinical trial and research in various healthcare domains.

Multimodal Imaging of Sarcopenia using Optical Coherence Tomography and Ultrasound in Rat Model

  • Jeon, Byeong Hwan;Chae, Yu-Gyeong;Hwang, Sang Seok;Kim, Dong Kyu;Oak, Chulho;Park, Eun-Kee;Ahn, Yeh-Chan
    • Journal of the Optical Society of Korea
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    • v.18 no.1
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    • pp.55-59
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    • 2014
  • Sarcopenia, or reduced muscle mass and volume, is due to various factors such as senile change, neuronal degeneration, drug, malignancy, and sepsis. Sarcopenia with the aging process has been evidenced by the decline in muscle mass by 0.5 to 1% per year with 3-5% reduction in muscle strength for 10 years between the ages of 40 and 50, and a 1-2% of decline of mass every year in people aged 60-70. Therefore, early diagnosis and understanding the mechanism of sarcopenia are crucial in the prevention of muscle loss. However, it is still difficult to image changes of muscle microstructure due to a lack of techniques. In this study, we developed an animal model using denervated rats to induce a rapid atrophy in the tibialis anterior (TA) and imaged its structural changes using optical coherence tomography (OCT) along with histologic and ultrasound analyses. Ultrasound showed changes of overall muscle size. Histology revealed that the atrophic TA muscle displayed an increased size variability of muscle fiber and inflammatory changes. Three dimensional OCT imaged the changes of perimysial grid and muscle fiber structure in real time without sacrifice. These observed advantages of multimodal imaging using OCT and ultrasound would provide clinical benefits in the diagnosis of sarcopenia.

Implementation of a Circuit for the Enhancement of Signal to Noise Ratios of Current Signal in a Artificial Heart (인공심장 전류 신호의 신호대 잡음비 개선을 위한 회로 구현)

  • Choi, J.H.;Lee, J.H.;Choi, W.W.;Ahn, J.M.;Kim, W.E.;Lee, J.J.;Om, K.S.;Choi, J.S.;Park, S.K.;Cho, Y.H.;Kim, H.C.;Min, B.G.
    • Proceedings of the KOSOMBE Conference
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    • v.1996 no.11
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    • pp.277-280
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    • 1996
  • We have developed a ground-isolation circuit in order to reduce the noise of the internal controller system for the total artificial heart(TAH) and ventricular assist device(VAD). Using the ground-isolation technique, we could transmit the analog target signal to other pheriperal device including IBM PC via RS232C and polygraph, with no noise. Experimental results of VAD showed that there was less impulsive noise in current signal which caused in our previous conventional system. Therefore it could be proved that implementation of isolation technique is very effective to improve the signal to noise ratios of analog signal transmission for TAH or VAD.

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A Study on Miniaturization of Digital Controller for both Implantable Total Artificial Heart (TAH) and Ventricular Assist Device (VAD) using PSD302 (PSD302를 이용한 완전 이식형 인공심장 및 심실보조장치 제어용 디지탈 콘트롤러 소형화에 관한 연구)

  • Lee, J.H.;Choi, J.H.;Lee, J.J.;Kim, W.E.;Om, K.S.;Choi, J.S.;Ahn, J.M.;Choi, W.W.;Park, S.K.;Cho, Y.H.;Kim, H.C.;Min, B.G.
    • Proceedings of the KOSOMBE Conference
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    • v.1996 no.11
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    • pp.273-276
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    • 1996
  • In the Total Artificial Heart (TAH) and Ventricular Assist Device (VAD), the size implanting the internal controller into human body is very serious problem. Hence, we need the size reduction of that controller for safe implantation. Using PSD302 chip for microcontroller-based applications, we could decrease the number of components in the digital control board and miniaturize the digital control board. We could replace a ROM, RAM, and a latch with that single chip, so the size of the newly developed board could be half the previous board.

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SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

  • Kim, Dong Hwi;Yong, Hyo Jeong;Mander, Sunam;Nguyen, Huong Thi;Nguyen, Lan Phuong;Park, Hee-Kyung;Cha, Hyo Kyeong;Kim, Won-Ki;Hwang, Jong-Ik
    • Biomolecules & Therapeutics
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    • v.29 no.3
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    • pp.331-341
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    • 2021
  • Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

Metformin ameliorates olanzapine-induced disturbances in POMC neuron number, axonal projection, and hypothalamic leptin resistance

  • Kim, Jaedeok;Lee, Nayoung;Suh, Sang Bum;Jang, Sooyeon;Kim, Saeha;Kim, Dong-Gyu;Park, Jong Kook;Lee, Keun-Wook;Choi, Soo Young;Lee, Chan Hee
    • BMB Reports
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    • v.55 no.6
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    • pp.293-298
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    • 2022
  • Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

Single-cell RNA sequencing identifies distinct transcriptomic signatures between PMA/ionomycin- and αCD3/αCD28-activated primary human T cells

  • Jung Ho Lee;Brian H Lee;Soyoung Jeong;Christine Suh-Yun Joh;Hyo Jeong Nam;Hyun Seung Choi;Henry Sserwadda;Ji Won Oh;Chung-Gyu Park;Seon-Pil Jin;Hyun Je Kim
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.18.1-18.11
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    • 2023
  • Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.