Yueh-Hsiung Kuo

Bio: Yueh-Hsiung Kuo is an academic researcher from China Medical University (Taiwan). The author has contributed to research in topics: Bark & Chemistry. The author has an hindex of 57, co-authored 618 publications receiving 12204 citations. Previous affiliations of Yueh-Hsiung Kuo include China Medical University (PRC) & Academia Sinica.

Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus.

Abstract: In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 microM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC50) and viral replication (EC50) were measured. The selective index values (SI = CC50/EC50) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with Ki values = 8.2 +/- 0.7 and 9.1 +/- 2.4 microM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.

Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin.

Abstract: Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC50=5.5 μg ml−1), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor κB (IκB) and the translocation of nuclear transcription factor-κB (NF-κB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-κB activation by impairing the binding of NF-κB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-κB·DNA complex formation. Structure–activity relationship analyses suggested that the catechol moiety and α,β-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-κB·DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate. Keywords: Ethyl caffeate, Bidens pilosa, NF-κB, COX-2, iNOS, PGE2 Introduction The nuclear factor-κB (NF-κB) is essential for host defense and inflammatory responses to microbial and viral infections (Li & Verma, 2002). In response to extracellular stimuli, such as bacterial lipopolysaccharide (LPS), tumor-necrosis factor-α (TNF-α), or other inflammatory mediators, the transcription factor NF-κB is often activated and subsequently facilitates the transcription of a number of genes involved in inflammation, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and specific cytokines (Bayon et al., 2003). The inhibitor of κB (IκB) kinase (IKK) complex is a central element of NF-κB-related signaling. IKK phosphorylates NF-κB-bound IκB complexes at two conserved serine residues within the IκB N-terminal regulatory domain. This targets IκB for ubiquitin-dependent degradation and allows the liberated NF-κB dimers to be translocated to the nucleus and bind to cognate DNA enhancer sequences that lead to the transcription of various genes (Karin et al., 2002). The other major extracellular signal transduction pathway stimulated by inflammatory mediators is the mitogen-activated protein kinase (MAPK) pathway (Guha & Mackman, 2001). MAPKs are a family of serine/threonine protein kinases composed of the p44 and p42 isoforms (also known as extracellular signal receptor-activated kinase ERK1 and ERK2), p38, and c-Jun NH2-terminal kinase (JNK) (Nishida & Gotoh, 1993; Han et al., 1994). It has been found that LPS, the key mediator in the inflammation response, can induce activation of these MAPK proteins in macrophage and other cell types (Hambleton et al., 1996; Chen & Wang, 1999; Guha & Mackman, 2001). Activation of p38, but not p44/p42 MAPK, by LPS resulted in the stimulation of NF-κB-specific DNA–protein binding and the subsequent expression of iNOS and nitric oxide (NO) release in RAW 264.7 macrophages (Chen & Wang, 1999). NF-κB and MAPKs are therefore known as important targets for anti-inflammatory molecules. Improper activation or upregulation of iNOS or COX-2 has been shown to be associated with the pathophysiologies of certain types of human cancers as well as inflammatory disorders (Beyaert, 2003). Therefore, the identification of naturally occurring phytocompounds that can suppress or downregulate the functions of iNOS or COX-2, or the activation of their upstream transcriptional factor NF-κB, may lead to the discovery of important anti-inflammatory therapeutics. Since inflammation is closely linked to the promotion of certain tumors, substances with potent anti-inflammatory activities are anticipated to exert chemopreventive effects on carcinogenesis (Surh et al., 2001). For instance, phenolic compounds, particularly those present in edible and medicinal plants, have been reported to possess substantial anticancer or cancer chemopreventive properties (Park & Pezzuto, 2002). Bidens pilosa (Asteraceae), commonly known as ‘hairy beggar-ticks' or ‘Spanish needles', is widely distributed in tropical and subtropical regions, and has been reported to possess antihyperglycemic (Ubillas et al., 2000), antihypertensive (Dimo et al., 2001; 2002), antiulcerogenic (Tan et al., 2000), hepatoprotective (Chin et al., 1996), immunosuppressive and anti-inflammatory (Pereira et al., 1999), antileukemic (Chang et al., 2001), antimalarial (Brandao et al., 1997), and antimicrobial (Khan et al., 2001) properties. B. pilosa has traditionally or anecdotally been used for the management of inflammatory diseases, and stomach and liver disorders. However, the cellular and molecular mechanisms underlying the anti-inflammatory properties of B. pilosa extract and its derived active compound are currently not well defined. In our previous study, we identified an ethyl acetate (EA) fraction partitioned from the ethanolic extract of fresh whole B. pilosa plants that significantly inhibited the LPS-induced NO production in RAW 264.7 cells (IC50=36 μg ml−1) (Chiang et al., 2004). In the present study, a bioactive phytocompound, ethyl caffeate that exhibits potent inhibitory effects on NO production in macrophages was identified from the bioactive EA fraction using bioactivity-guided fractionation. Ethyl caffeate was then investigated for its anti-inflammatory mechanisms in vitro in LPS-stimulated macrophages, and in vivo using TPA-treated mouse skin system. The effects of ethyl caffeate on the activation of NF-κB, MAPKs, as well as on the downstream mediators of inflammation, such as iNOS, COX-2 and prostogladin E2 (PGE2), were investigated.

Type 1 diabetes

Abstract: Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Role of WHO.

Abstract: OVERVIEW The GRA Marketing Internship Program is offered to students who are interested in gaining valuable work experience through efforts in marketing, membership, sales, and events. Interns work directly to assist the Director of Marketing and Communications on various tasks relating to upcoming GRA events. During this internship, students will work a minimum of 10 hours a week and a maximum of 20 hours a week. Students are encouraged to earn credit for their internship, however this is a paid internship. Students interested in obtaining credit for their internship must consult their academic advisor or the intern coordinator at their academic unit.