α-Viniferin (AVF), a trimer of resveratrol, is known to have an anti-inflammatory effect via inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). It has been reported that up-regulated COX-2 and iNOS are expressed in colon cancer tissues of humans and rodents as well as pre-neoplastic aberrant crypt foci (ACF) of rodents. In this study, chemopreventive effects of AVF were assessed in Caco-2 cells as well as azoxymethane (AOM)-induced colorectal tumorigenesis in mice. Anti-tumor effect of AVF with regards to apoptotic induction was assessed by TUNEL and caspase-3 expression in human colon cancer Caco-2 cells. For development of ACF, AOM was administered with to mice intraperitoneally at a dose of 10 mg/kg once a week for 3 weeks. To induce colitis-related colon cancer, mice were administered a single dose of AOM (10 mg/kg) and 2% dextran sodium sulfate in drinking water. Mice treated with 0.05 and/or 0.1 mg of AVF by gavage showed significantly reduced development of ACF and colorectal tumors. Immunofluorescence detection in Caco-2 cells showed reduced COX-2 and iNOS expression, whereas cleavage of caspase-3 and apoptotic cell numbers increased upon AVF treatment. Immunostaining showed reduced expression levels of COX-2 and iNOS expression along with increased cleaved caspase-3 expression increased upon AVF treatment. These results suggest that AVF has chemopreventive effects on colorectal cancer via anti-inflammatory potential and pro-apoptotic activity.

Cytokines are known to function as regulatory molecules that can be produced by virtually every nucleated cell type in the body, including lymphocytes, monocytes/macrophages, epithelial cells, fibroblasts, and many others. Cytokines include lymphocyte-derived factors (lymphokines), monocyte-derived factors (monokines), hematopoietic factors (colony-stimulating factors), connective tissue/ growth factors, and chemotactic chemokines. Cytokines released in response to infection can affect tumor development in different ways. When exposed to infectious agents, cytokines are secreted by sentinel cells, such as macrophages and dendritic cells. These cytokines include interleukin 1 (IL-1) and tumor necrosis factor-α, as well as others, such as IL-6, IL-12, and IL-18. When released in sufficient quantities, these molecules can cause inflammation. Chronic inflammation is highly associated with tumor initiation, promotion, and progression. In this article, we review the roles and mechanisms of cytokines in tumor development.

In all living organisms, respiration may lead to oxidative stress, a state where increased formation of reactive oxygen species overwhelms host protection and subsequently induces DNA damage, lipid peroxidation, and protein denaturation. As a phenolic acid, chlorogenic acid occurs ubiquitously in food. It has been proven to have a number of biological effects in vitro and in vivo, including antioxidant, anti-inflammatory, and anticarcinogenic properties. Therefore, to some extent, chlorogenic acid can promote human health, and hopefully provide new methods for treatment of chronic disease. Recent studies have focused on the antioxidant properties of dietary polyphenols. The in vitro data often conflict with results obtained from in vivo studies on the antioxidant capacity of plasma or the resistance of plasma and lipoproteins to oxidation ex vivo after consumption of polyphenol-rich foods by human subjects. These inconsistencies are likely explained by the limited bioavailability of dietary polyphenols and their extensive metabolism in humans. Polyphenols exert multifaceted actions, and any clinical application using these substances should be based on a precise understanding of the physiologically relevant mechanisms.

Sepsis is a clinical syndrome defined as a systemic inflammatory response to infection. Eritoran is a synthetic lipid A derivative that competes with lipopolysaccharide in binding to the identical site of myeloid differentiation-2/toll-like receptor 4 complex. Eritoran is effective in decreasing the septic mortality of Gram-negative bacteria-infected animals. Eritoran has been highlighted as a candidate drug for treatment of endotoxemia in phase I clinical studies with healthy human volunteers. A phase II trial of eritoran has been conducted in patients with severe sepsis. Intravenous infusion of eritoran reduced the mortality rate, as compared with the placebo group, in sepsis patients at a high risk of mortality according to acute physiology and chronic health evaluation-II scores. A phase III study of eritoran was completed in 2011. The results appear to be disappointing as no statistically significant difference in all-cause mortality was observed between the eritoran treatment group and the placebo group on day 28 in sepsis patients with a high risk of death. In this review, we focus on the rationale for the use of eritoran in treatment of sepsis as well as its clinical applications.

Microbial lipopolysaccharide (LPS) is an endotoxin conveying the surface receptor complex of toll-like receptor 4 (TLR4)-myeloid differentiation 2 (MD-2) in innate immune cells through ancillary proteins such as LPS-binding protein and CD14. However, TLR4 alone is not sufficient for recognition of LPS. MD-2 is essential for sensing the lipid A domain of LPS and for triggering LPS-induced TLR4 activity across the plasma membrane. Therefore, lipid A domain and its binding to MD-2 are potential drug targets for intervention in endotoxemia as well as other disorders associated with LPS etiology. Here, we reviewed MD-2 as a drug target focused on drug candidates-targeting TLRs, transport of microbial LPS into TLR4/MD-2, crystal structure of TLR4/MD-2 alone, crystal structure of TLR4/MD-2 with bound LPS, lipid A derivatives as MD-2 antagonist, non-lipid antagonists of LPS binding to MD-2, and human disorders-implicated with TLR4/ MD-2. This review could be helpful to understanding the biology of TLR4/MD-2, and suggests the importance of MD-2 as a therapeutic target against inflammatory diseases due to infection.

The Notch signaling pathway regulates cell proliferation, apoptosis and cell fate decision. Recent preclinical and clinical evidence supports a pro-oncogenic function for Notch signaling in several solid tumors including breast and prostate cancer. Consequently, there is increasing interest in targeting Notch signaling therapeutically in cancer patients. Notch inhibitors, particularly gamma-secretase inhibitors, are being investigated as candidate cancer therapeutic agents. However, rational targeting of Notch signaling in cancer will require a systematic exploration of several areas that remain incompletely understood. Therefore, a clear understanding of the Notch signaling and its cross-talk with other signaling cascade will increase our ability to design rational combination regimens for cancer therapy.

In the present study, we have demonstrated that a novel synthetic chemical JSH-21 of N¹-Benzyl-4-methylbenzene-1,2-diamine could inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages RAW 264.7. The JSH-21 showed an IC50 value of 9.2 uM on the LPS-induced NO production. Furthermore, JSH-21 attenuated LPS-induced mRNA and protein levels of inducible NO synthase (iNOS) in the cells, as well as inhibited LPS-induced iNOS promoter activity. These results indicates hat the compound could down-regulate iNOS expression at the transcription level. Since NF-kB activation is a key mechanism in the expression of LPS-inducible iNOS gene, we further examined whether JSH-21 could affect LPS-induced NF-kB activation. JSH-21 inhibited LPS-induced nuclear import of NF-kB p65 in macrophages RAW 264.7 and sequentially prevented NF-kB transcriptional activity. However, JSH-21 was not effective in a LPS-induced degradation of cytoplasmic IkB-alpha in the cells. These results suggest that JSH-21 could inhibit LPS-induced NF-kB activation targeting nuclear import of NF-kB, an event downstream IkB degradation. Taken together, this study may provide a pharmacological potential of JSH-21 in the NO- or NF-kB-associated inflammatory disorders.

역사교과서는 사람들의 가치관 형성에 중요하기 때문에 사실에 기초해야 한다. 역사교과서 편찬은 최신 연구 성과를 반영하는 토대 위에서 표준과정과 심의과정을 체계적으로 운영 해야 한다. 그런데 일본은 대내외 정치적 문제 때문에 독도를 포함한 과거 역사를 사실과 다른 역사로 확대 재생산하고 있다. 일본은 2014년 기존 교과서에서 독도가 부분적으로 기술된 것에 만족하지 못하고, 교과서에 들어갈 내용을 해설서에 구체적으로 기술하였다. 일본은 2015 년 독도와 관련하여 일본의 고유영토, 1905년 시마네현의 편입, 1954년 한국의 불법점거, 국제사법재판소의 평화적 해결 등의 내용을 일본 중학교 사회과 교과서에 대폭적으로 강화 되었다. 일본은 중학교 사회과 교과서 검정을 통해서 내셔널리즘을 강조하는 독도 교육을 전면적으로 강조하였다. 이것은 일본이 독도를 영토문제로 제기하는 수준을 넘어, 역사문제로 전면적으로 확대시켰다는 것을 의미한다. 결국 일본의 사회과 교과서는 동북아의 평화적 미래보다는 아베정권의 정치적 도구로 전락했다. 일본은 독도와 관련하여 초등학교에서 시각적인 측면, 중·고등학교에서 논리적인 측면을 강조하였다. 일본은 주로 근현대사 위주의 독도 교육을 실시하고 있다. 일본은 과거 고등학교 지리와 공민 교과서에 독도를 영토문제로 제기하는 수준을 넘어서, 현재 역사 교과서에 내셔널리즘을 강조하는 독도 교육을 전면적으로 실시하였다. 한국은 독도와 관련하여 초·중·고등학교에서 역사적 사실을 강조하였다. 한국은 주로 전근대와 근대사 중심의 독도 교육을 실시하고 있다. 한국 사회과 교과서는 독도에 관한 국제법적 측면, 논리적인 측면에 대한 보강이 필요하다. 향후 한국의 사회과 교과서는 근현대 일본이 동북아의 역사 갈등을 유도했다는 서술이 필요하다. 또한 한중일의 근현대 역사 교과서의 공통편찬이 중요하다. 왜냐하면 유럽과 달리 동북아의 역사 갈등이 해결되지 않았기 때문이다.