Soowon Kang

Ginseng, the 'Immunity Boost': The Effects of Panax ginseng on Immune System

Thousands of literatures have described the diverse role of ginseng in physiological processes such as cancer, neurodegenerative disorders, insulin resistance, and hypertension. In particular, ginseng has been extensively reported to maintain homeostasis of the immune system and to enhance resistance to illness or microbial attacks through the regulation of immune system. Immune system comprises of different types of cells fulfilling their own specialized functions, and each type of the immune cells is differentially influenced and may be simultaneously controlled by ginseng treatment. This review summarizes the current knowledge on the effects of ginseng on immune system. We discuss how ginseng regulates each type of immune cells including macrophages, natural killer cells, dendritic cells, T cells, and B cells. We also describe how ginseng exhibits beneficial effects on controlling inflammatory diseases and microbial infections.

Age-Associated Changes in MicroRNA Expression in Bone Marrow Derived Dendritic Cells

MiRNAs have shown to regulate aging process at the level of cellular senescence, tissue aging, and lifespan of whole organism. Given that many miRNAs also function as important regulators of hematopoietic system as well as aging process, it is highly likely that miRNAs would be involved in the changes of myeloid function and differentiation during aging. Therefore, here we examine differential expression of miRNAs in aged myeloid lineage cells and assess if altered miRNA expression pattern would reflect the change of miRNA targets and related function. We demonstrated that the expressions of myelogenic miRNAs such as miR-155, miR-223, miR-146a, miR-146b, miR-132, miR-142-5p, and miR-142-3p were increased in aged bone marrow derived dendritic cells (BMDC) under normal and activated conditions. We also observed that the expressions of IRAK1 and TRAF6, the targets of miR-146a, and DC-SIGN, a target of miR-155 were diminished while miR-146a and miR-155 were augmented during aging. In addition, we found that the production of pro-inflammatory cytokines, which is mediated by the activation of NF-kB pathway via IRAK1 and TRAF6, was greatly reduced in aged BMDC. Taken together, our data reveal that age-associated changes occur in miRNA expression in BMDC, and this altered miRNA expression affects miRNA target expression and compromises BMDC function such as cytokine production during aging.

T Cell Stimulatory Effects of Korean Red Ginseng through Modulation of Myeloid-Derived Suppressor Cells

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-γ, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

Macro and Small over Micro: Macromolecules and Small Molecules that Regulate MicroRNAs

Given the correlation between the deregulation of specific miRNAs and disease onset, it is critical to identify miRNA regulators that effectively control miRNAs involved in the pathogenesis of target diseases. This review provides the latest update on oligonucleotide- and small-molecule-based miRNA regulators, and discusses assays developed to screen for small-molecule regulators.

Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus

Background Ginsenosides are the major components of Panax ginseng Meyer, an herbal medicine used for the treatment of various diseases. Different ginsenosides contribute to the biological properties of ginseng, such as antimicrobial, anticancer, and immunomodulatory properties. In this study, we investigated the antiviral effects of 15 ginsenosides and compound K on gammaherpesvirus. Methods The antiviral activity of ginsenosides was examined using the plaque-forming assay and by analyzing the expression of the lytic gene. Results 20(R)-Ginsenoside Rh2 inhibited the replication and proliferation of murine gammaherpesvirus 68 (MHV-68), and its half-maximal inhibitory concentration (IC50) against MHV-68 was estimated to be 2.77 μM. In addition, 20(R)-ginsenoside Rh2 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpesvirus in the Kaposis sarcoma-associated herpesvirus (KSHV)-positive cell line BC3. Conclusion Our results indicate that 20(R)-ginsenoside Rh2 can inhibit the replication of mouse and human gammaherpesviruses, and thus, has the potential to treat gammaherpesvirus infection.

Contribution of CD24 polymorphisms to autoimmune disease

PURPOSE To determine the relationship between two CD24 polymorphisms, rs8734/rs52812045 and rs3838646, and autoimmune disease. DESIGN Meta-analysis. METHODS The Medline, EMBASE, Web of Science, and Cochrane Library databases were searched for studies reporting the association between CD24 polymorphisms and autoimmune disease. Two of the authors selected eligible studies and extracted and analyzed the data independently. RESULTS Compared with carriers of the C allele (CC, CT, CT+CC), individuals homozygous for the T allele (TT) and heterozygous (CT+TT) at rs8734/rs52812045 have a higher incidence of autoimmune disease, whereas rs3838646 is not associated with autoimmune disease. Subgroup analysis found an increased risk of multiple sclerosis with the TT vs. CC, TT vs. CT, and TT vs. CC+CT alleles. CONCLUSION The CD24 polymorphism rs8734/rs52812045 contributes to the development of autoimmune disease.

Development of a gene carrier using a triblock co-polyelectrolyte with poly(ethylene imine)-poly(lactic acid)-poly(ethylene glycol)

The success of gene therapy mainly depends on the carriers for effective gene delivery. A non-viral vector using a cationic block co-polyelectrolyte, PEI-PLA-PEG polyethyleneimine-poly(lactic acid)-poly(ethylene glycol)) was developed as a potential gene carrier. The cationic PEI-PLA-PEG showed less toxicity compared to PEI and formed a gene nanocomplex (termed polyplex) by interaction with plasmid DNA or small interference RNA. The polyplex showed smaller particle size and greater positive zeta potential by increasing the high polymer nitrogen/DNA phosphate ratio. The polyplex with a nitrogen/DNA phosphate ratio of 16 or 32 demonstrated higher gene transfection by fluorescence imaging, flow cytometry measurement, and β-galactosidase activity. In particular, the polyplex with therapeutic histone deacetylase small interference RNA at nitrogen/DNA phosphate ratio 16 showed the most favorable properties with definite tumor growth inhibition. The synthetic PEI-PLA-PEG also showed less toxicity and would, therefore, be a great potential gene carrier, particularly given that small interference RNA delivery does not increase the charge density of small interference RNA due to the formation of a stable complex through conjugation with PLA-PEG.

Identification of aminosulfonylarylisoxazole as microRNA-31 regulators

The discovery of small-molecule regulators of microRNAs remains challenging, but a few have been reported. Herein, we describe small-molecule inhibitors of miR-31, a tumor-associated microRNA (miRNA), identified by high-throughput screening using a cell-based reporter assay. Aminosulfonylarylisoxazole compounds exhibited higher specificity for miR-31 than for six other miRNAs, i.e., miR-15a, miR-16, miR-21, miR-92a-1, miR-146a, and miR-155, and increased the expression of miR-31 target genes. The down-regulation of mature miR-31 was observed, while its precursor form increased following treatment with the compounds. Thus, the compounds may target the processing of pre-miR-31 into mature miR-31 and thereby inhibit the production of mature miR-31.

Regulation of the viral life cycle by murine gammaherpesvirus 68 microRNAs.

Abstractγ-Herpesviruses (γHV) such as Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus are important human pathogens involved in lymphoproliferation and tumorigenesis. Murine gammaherpesvirus 68 (MHV-68, γHV-68) is an effective model for the study of γHV pathogenesis and host-virus interaction because it is closely related to human γHV. Similarly to human γHV, MHV-68 encodes 15 microRNAs (miRNAs). Although their functions remain unknown, they are thought to regulate the viral life cycle or host-virus interactions, similarly to other human γHV. Herein, we established stable cell lines expressing MHV-68 miRNAs and investigated the role of MHV-68 miRNAs in the regulation of viral life cycle. We found that mghv-miR-M1-1, -3, -5, -7, -8, -9, -10, -11, -13, and -15 repressed MHV-68 lytic replication by down-regulating expression of the replication and transcription activator (RTA) gene, whereas mghv-miR-M1-2, -4, -6, and -12 induced lytic replication by up-regulating RTA. We confirmed that the decrease in viral replication caused by mghv-miR-M1-1 was abolished by inhibition of miRNA expression via miRNA inhibitor treatment. In addition, we observed that mghv-miR-M1-1 down-regulated c-Jun indirectly and decreased cytokine production, suggesting that mghv-miR-M1-1 may inhibit MHV-68 lytic replication by inhibiting the activator protein 1 (AP-1) signaling pathway.

Computational prediction of competitive endogenous RNA

MicroRNAs (miRNAs) play an important role in the post-transcriptional regulation of gene expression by pairing target messenger RNAs (mRNAs). As the abnormal expression of miRNAs has been implicated in various diseases, there has been many studies on regulating the expression level of miRNA, including “miRNA sponges.” miRNA sponges, which are artificial miRNA decoys, contain complementary binding sites to a target miRNA and regulate the expression level of target miRNAs. As competitive endogenous RNAs (ceRNAs) have been found in a recent study, there have been many efforts to find natural miRNA sponges. However, there are no related studies about the computational approach using the pairwise interactions of numerous mRNA-miRNA pairs. In this study, a computational approach to find candidates of natural miRNA sponges is proposed. Whole miRNA binding sites with query miRNA and the secondary structures of reference mRNA are predicted, followed by calulating the adjusted minimum free energy (AMFE) as the total score. We can quantitatively compare the interactions between miRNAs and target mRNAs by using this proposed approach. Thirty viral miRNAs and about 300 of thousands of human mRNAs are used in this study. As a results, the top 20 natural miRNA sponge candidates are recorded. The results are expected to provide appropriate knowledge before in vivo experiments to validate the identification of miRNA sponges.