Targeted delivery of growth factors in ischemic stroke animal models

Rhim, Taiyoun,Lee, Minhyung Informa UK (Ashley Publications) 2016 Expert opinion on drug delivery Vol.13 No.5

유전체 연구의 과거 현재 그리고 미래

임태연(Taiyoun Rhim) 한양대학교 고령사회연구원 2011 한양고령사회논집 Vol.2 No.2

인간지놈프로젝트의 종료가 선언된 지 벌써 8년이 지났다. 사람 DNA전부의 서열이 결정된 이 획기적인 사건은 생명과학 분야 및 의약학 분야의 연구에 있어 획기적인 변화가 올 것으로 기대되고 있다. 가설기반의 연구에서 데이터기반의 연구로 패러다임이 변화하며, 특히 생명과학분야에서는 인체를 이루는 DNA의 염기 서열이 무슨 의미를 가지며 어떠한 생체 작용과 연관이 되는지에 대한 연구가 집중적으로 이루어 질것으로 예상되고 있다. 본 문에서는 특히 질환과 유전체에 대한 관련성을 연구하는 분야에서 현재까지 어떠한 연구가 이루어져왔으며 또한 생명과학 및 의약학 분야에서 어떠한 연구들이 이루어질지 전망해 보고자 한다. It had been about 8 years since the human genome project complete. As a result of the work of the Human Genome Project, now we know the whole DNA sequence of human genetic material. The human genome project is expected to immensely benefit especially biological and medical science. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that afflict mankind, as well as the many multi-functional diseases in which genetic predisposition plays an important role. In this review, we will overview of past and present works on disease genomics, especially in terms of SNP, transcriptomics, proteomics and even systems biology. And we describe little about our prospect.

Complement C3a and C4a Increased in Plasma of Patients with Aspirin-induced Asthma

Lee, Seung-Ha,Rhim, TaiYoun,Choi, Yun-Sung,Min, Ji-Won,Kim, Sung-Ho,Cho, Sun-Young,Paik, Young-Ki,Park, Choon-Sik American Thoracic Society 2006 American journal of respiratory and critical care Vol.173 No.4

<P>RATIONALE: Aspirin-induced asthma (AIA) is a distinct clinical syndrome that affects up to 10% of adults with asthma. Although eicosanoid metabolites appear to play an important role in AIA, the exact pathogenic mechanism for the syndrome remains obscure. In addition, the proposed mechanism fails to explain why aspirin does not cause bronchoconstriction in all individuals. OBJECTIVES: We aimed to identify proteins that were differentially expressed in between AIA and aspirin-tolerant asthma (ATA) plasma. Methods and Main Results: By using a proteomics approach, six proteins were found to be differentially expressed in plasma between patients with AIA and patients with ATA at baseline, and eight proteins were significantly up- or down-regulated after aspirin challenge in patients with AIA. These proteins, which were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, can be classified into four groups: complement components, apolipoproteins, modified albumin, and unknown proteins. Among them, the complement component levels in plasma were validated by using ELISA. Plasma concentrations of C3a and C4a were higher in patients with AIA (n = 30) than in patients with ATA (n = 24). After the aspirin challenge, C3 decreased in both patients with AIA and those with ATA, but the C3a concentration increased in the AIA patient group (p = 0.019). Moreover, C3a and C4a levels and the ratios of C3a/C3 and C4a/C4 were correlated with the changes of FEV(1) values after aspirin challenge. CONCLUSIONS: Aspirin intolerance may be related to alterations in the levels of complements, as well as those of lipoprotein and other proteins.</P>

Application of proteomics in asthma research.

Park, Choon-Sik,Rhim, Taiyoun Future Drugs Ltd 2011 Expert review of proteomics Vol.8 No.2

<P>Bronchial asthma is caused by allergic airway inflammation, resulting in reversible airway obstruction, characterized by airway hyper-responsiveness, bronchoconstriction, increased mucus secretion and an increase in lung vessel permeability. The pathophysiological changes in asthma have been attributed to the altered expression of biologically plausible proteins associated with transcriptional pathways, inflammatory mediators, chemokines, cytokines, apoptosis and cell proliferation. Such multifactorial diseases characteristically involve an interplay of many genetic variations of molecular and biochemical pathways and their interactions with environmental factors. The complex nature of the asthma phenotype, together with genetic heterogeneity and environmental influences, has made it difficult to uncover the aspects that underlie this common disease. Recently, genomic and proteomic technologies have been developed to identify associations between genes, proteins and disease. This approach, called 'omics biology', aims to recognize early onset of disease, institute preventive treatment and identify new molecular targets for novel drugs in multifactorial diseases. This article reviews examples of how proteomic technology can be used to find asthma marker proteins (from the cell model to clinical samples). Identification of protein changes in different stages of asthma could provide further insights into the complex molecular mechanisms involved in this disease. These studies provide new insights for finding novel pathological mediators and biomarkers of asthma.</P>

Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

Choi, Moonhwan,Ban, Taehyun,Rhim, Taiyoun Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.2

Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.

Effect of Retinoic Acid on Epithelial Differentiation and Mucin Expression in Primary Human Corneal Limbal Epithelial Cells

Kim, Sun Woong,Seo, Kyoung Yul,Rhim, Taiyoun,Kim, Eung Kweon IRL Press 2012 Current eye research Vol.37 No.1

<P><I>Purpose:</I> Retinoic acid (RA) is essential for epithelial differentiation and maintenance of the mucous phenotype. This study investigated the effect of RA on corneal epithelial differentiation and mucin expression in a primary human corneal limbal epithelial cell (HCLEC) culture model.</P><P><I>Methods:</I> HCLECs were grown in RA-supplemented media at various concentrations (0, 10<SUP>−9</SUP> to 10<SUP>−6</SUP> M). Stratified HCLECs were examined using immunohistochemical or immunofluorescent staining for p63, ABCG2, CK3, CK19, and Western blotting for ABCG2 and CK12 to assess differentiation. Ultrastructural morphology was investigated using scanning and transmission electron microscopy. They were incubated with rose bengal dye to examine barrier function. The effects of RA on the expression of MUC1, -4, and -16 were analyzed by immunohistochemistry, quantitative real-time PCR and Western blot analysis.</P><P><I>Results:</I> HCLEC grown without RA showed hyperkeratosis, whereas those grown with 10<SUP>−8</SUP> to 10<SUP>−7</SUP> M RA induced non-keratinized stratified epithelium with a normal appearance. Under these conditions, p63, ABCG2, CK3, CK19, MUC1, -4, and -16 staining patterns were similar to <I>in vivo</I> limbal epithelium. A higher concentration (10<SUP>−6</SUP> M) of RA resulted in abnormal differentiation. HCLECs grown with RA were tightly apposed and maintained intact barrier function against dye penetration. In addition, MUC1, -4, and -16 expressions were highly associated with RA concentrations.</P><P><I>Conclusions:</I> This study showed that cultured HCLEC could mimic physiologic and functional phenotypes by controlling RA concentrations in medium. Also, our results suggested modulating effect of RA on differentiation and mucin expression in corneal epithelium.</P>

Expression, Purification, and Characterization of Prothrombin Kringle 2

Kim, Soung Soo,Park, Chan-Soo,Rhim, TaiYoun,Kim, Eunkyung The Korea Science and Technology Center 1999 BMB Reports Vol.32 No.2

Previously, we reported that the prothrombin kringle 2 (fragment 2), induced by LPS administration into rabbit, inhibited bFGF-stimulated BCE cell growth (Lee et al., 1998). In this study, we cloned and overexpressed the kringle 2 domain of rabbit and human prothrombin as a fusion protein with the pelB leader sequence in E. coli using the T7 promoter. The fusion protein was cleaved during translocation into the periplasmic space, and cleaved recombinant protein was readily isolated from whole cell lysate by DEAE-Sepharose and Sephacryl S-200 gel filtration chromatography. Both the recombinant rabbit and human prothrombin kringle 2 showed very similar biochemical and functional characteristics to the rabbit prothrombin kringle 2 purified from rabbit serum, in terms of abnormal electrophoretic migration and endothelial cell growth inhibitory activity.

Combined delivery of temozolomide and the thymidine kinase gene for treatment of glioblastoma

Choi, Eunji,Han, Jaesik,Tan, Xiaonan,Oh, Jungju,Lee, Dahee,Rhim, Taiyoun,Lee, Minhyung Informa Healthcare 2017 JOURNAL OF DRUG TARGETING Vol.25 No.2

A Disintegrin and Metalloproteinase 33 Protein in Patients with Asthma : Relevance to Airflow Limitation

Lee, Ji-Yeon,Park, Sung-Woo,Chang, Hee Kyoung,Kim, Ho Young,Rhim, TaiYoun,Lee, June-Hyuk,Jang, An-Soo,Koh, Eun-Suk,Park, Choon-Sik American Thoracic Society 2006 American journal of respiratory and critical care Vol.173 No.7

<P>BACKGROUND: ADAM33 has been identified as a novel asthma susceptibility gene in genomewide screening and association studies. High-level expression in smooth muscles and fibroblasts suggests that ADAM33 plays a role in airway remodeling in patients with asthma. METHODS: The ADAM33 protein was identified in the bronchoalveolar lavage (BAL) fluids of patients with asthma and normal control subjects using Western blotting antibody against the catalytic domain. ADAM33 expression was analyzed using immunohistochemical staining of mucosal biopsy specimens. The levels of ADAM33 protein in the BAL fluids were measured by dot blotting, and were correlated with the FEV1 values of the patients with asthma. RESULTS: Western blot analysis revealed the presence of the ADAM33 protein, with a molecular mass of approximately 55 kD in the BAL fluids. ADAM33 was expressed in the smooth muscles and basement membranes of almost all the patients with asthma, but was absent in the normal control subjects. The ADAM33 levels were increased significantly in patients with moderate to severe asthma and in patients with mild asthma, as compared with normal control subjects (p = 0.001 and p = 0.016, respectively). The ADAM33 protein levels correlated inversely with the FEV(1)% predicted in the patients with asthma (r = -0.486, p = 0.018). CONCLUSIONS: ADAM33 is associated with asthma development, and the levels of ADAM protein are related to asthma severity.</P>

Calnexin as a dual-role biomarker: antibody-based diagnosis and therapeutic targeting in lung cancer

( Soyeon Lim ),( Youngeun Ha ),( Boram Lee ),( Junho Shin ),( Taiyoun Rhim ) 생화학분자생물학회 2024 BMB Reports Vol.57 No.3

Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.