Oral bacterial infections substantially affect the development of various periodontal diseases and oral cancers. However, the molecular mechanisms underlying the association between Fusobacterium nucleatum (F. nucleatum ), a major periodontitis (PT)-associated pathogen, and these diseases require extensive research. Previously, our RNAsequencing analysis identified a few hundred differentially expressed genes in patients with PT and peri-implantitis (PI) than in healthy controls. Thus, in the present study using oral squamous cell carcinoma (OSCC) cells, we aimed to evaluate the effect of F. nucleatum infection on genes that are differentially regulated in patients with PT and PI. Human oral squamous cell carcinoma cell lines OSC-2O, HSC-4, and HN22 were used. These cells were infected with F. nucleatum at a multiplicity of infection of 100 for 3 hours at 37℃ in 5% CO2. Gene expression was then measured using reverse-transcription polymerase chain reaction. Among 18 genes tested, the expression of CSF3, an inflammation-related cytokine, was increased by F. nucleatum infection. Additionally, F. nucleatum infection increased the phosphorylation of AKT, p38 MAPK, and JNK in OSC-20 cells. Treatment with p38 MAPK (SB202190) and JNK (SP600125) inhibitors reduced the enhanced CSF3 expression induced by F. nucleatum infection. Overall, this study demonstrated that F. nucleatum promotes CSF3 expression in OSCC cells through p38 MAPK and JNK signaling pathways, suggesting that p38 MAPK and JNK inhibitors may help treat F. nucleatum-related periodontal diseases by suppressing CSF3 expression.

This research investigated the immunoenhancing effect through the intracellular MAPKs and NF-B signaling pathways in macrophages activated by crude polysaccharides (YBP) of barley sprouts. YBP extracted from barley sprouts is composed of xylose (25.8%), arabinose (24.1%), galactose (23.4%), and galacturonic acid (11.7%). YBP did not affect the cytotoxicity and showed superior secretion of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)- by RAW264.7 cells. Also, YBP dose dependently increased IL-6, TNF-, and inducible nitric oxide synthase (iNOS) mRNA gene expression. In the western blot, YBP strongly induced the phosphorylation of the p38, JNK, ERK, and IB pathways in RAW 264.7 cells. In the anti-pattern recognition receptor (anti-PRRs) assay, the effect of YBP on NO secretion strongly decreased toll-like receptor (TLR) 4 and Dectin1 antibodies, whereas IL-6 and TNF- secretion by YBP mainly decreased SR and CD14. Therefore, we concluded that YBPinduced NO, IL-6, and TNF- were secreted via the MAPKs, while NF-B pathways through TLR4, Dectin1, SR, and CD14 receptors existed in a macrophage surface and were involved in the immunoenhancing effect.

This study summarizes the recent cutting-edge approaches for dentin regeneration that still do not offer adequate solutions. Tertiary dentin is formed when odontoblasts are directly affected by various stimuli. Recent preclinical studies have reported that stimulation of the Wnt/β-catenin signaling pathway could facilitate the formation of reparative dentin and thereby aid in the structural and functional development of the tertiary dentin. A range of signaling pathways, including the Wnt/β-catenin pathway, is activated when dental tissues are damaged and the pulp is exposed. The application of small molecules for dentin regeneration has been suggested as a drug repositioning approach. This study reviews the role of Wnt signaling in tooth formation, particularly dentin formation and dentin regeneration. In addition, the application of the drug repositioning strategy to facilitate the development of new drugs for dentin regeneration has been discussed in this study.

Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.

Rutin은 메밀에 함유되어 있는 것으로 잘 알려져 있는 flavonoid 물질로서, 최근 연구들에서 rutin의 항염증 및 암예 방 활성이 보고되어져 왔다. 그러나, rutin의 암예방 활성과 관련된 분자생물학적 기전에 대한 연구는 아직까지 미비 한 실정이다. 따라서, 본 연구에서는 발암 과정 중 하나인 세포의 악성 변형을 EGF로 유도하여 rutin이 이를 억제하는 지 여부를 확인하는 실험을 진행하였으며, 그 분자생물학적 기전을 규명하고자 하였다. Soft agar assay 실험 결과, rutin은 EGF로 유도된 세포의 악성 변형을 25 μM, 50 μM 100 μM에서 농도별로 감소시켰다. 또한 EGF로 유도된 MEK/ERK 및 MKK4/JNK 신호전달체계의 인산화를 저해하였다. 그러나 이와는 대조적으로 rutin은 EGF로 유도된 MKK3/6/p38 신호전달체계 인산화는 감소시키지 못하는 것으로 확인되었다. 이상의 연구결과들은 rutin이 암화 과정 중 발생되는 세포의 악성변형 과정을 촉진시킨다고 잘 알려져 있는 MEK/ERK 및 MKK4/JNK 신호전달체계의 활성화 를 억제함으로써 암예방 활성을 나타낸다는 것을 제시하고 있으며, 이는 메밀의 생리활성 성분인 rutin의 암예방 생리 활성 소재로서의 이용 가능성을 보여주는 중요한 연구 결과라 할 수 있겠다. 또한 위 연구결과는 MEK/ERK 및 MKK4/JNK 신호전달 체계를 표적으로 하는 생리활성 소재 탐색에도 활용 가능할 것으로 생각되어진다.

It is well established that mammalian cumulus cell (CC) expansion requires BMP15 (bone morphogenetic protein bone morphogenetic protein 15) and GDF9 (growth differentiation factor 9). However, the mechanisms of the factors in CC expansion are largely unclear. This study was conducted to examine the two paracrine factors and their receptor SMAD intracellular signaling mechanism of mediating porcine CC expansion and oocyte maturation, and to compare COCs (Cumulus–oocyte complexes) maturation to DOs (Denuded oocytes). COCs and DOs were in vitro matured in medium with FSH, LH and TGFB superfamily antagonists. Our results showed that the expansion of COCs was unaffected by addition of GDF9 and BMP15 recombinant protein, but cumulus cell proliferation and DOs maturation rate were enhanced. The mRNA expressions of SMAD receptor confirmed that oocytes secreted factors that activate SMAD3,4 and SMAD1 in granulosa cells and oocytes, but unaffected SMAD2. Treatment of COCs with a SMAD2/3 phosphorylation inhibitor (SB431542) inhibited CC expansion and expression of TNFAIP6. SB431542 also was revealed to inhibit DOs maturation. The activation of CC SMAD signaling by oocytes, and the requirement of SMAD2/3 signaling for expansion and oocyte maturation were studied in pig. Nonetheless, porcine oocyte maturation without SMAD2/3 signaling is likely to be needed for optimal matrix formation, but also BMP15 and GDF9 is likely to be needed in oocyte.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear factor-kB(NF-kB) determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce NF-kB and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

Recently, as a natural substance has been emphasized interest in research to enhance the immune function. Green lettuce (Lactuca sativa L.) is a popular vegetable used fresh and it contains various phytochemicals and antioxidant compounds, and has been reported to have various physiological activities such as antibacterial, antioxidant, antitumor and anti-mutagenic. However, only a few studies have investigated on the mechanism of action of immune-enhancing activity of lettuce. Therefore, in this study, the immunomodulatory activities and potential mechanism of action of Green lettuce extracts (GLE) were evaluated in the murine macrophage cell line RAW264.7. GLE significantly increased NO levels by RAW264.7 cells, as well as expressions of immunomodulators such as iNOS, COX-2, IL-1β, IL-6, IL-12, TNF-α and MCP-1. Although GLE activated ERK1/2, p38, JNK and NF-κB, GLE-mediated expressions of immunomodulators was dependent on p38, JNK and NF-κB. In addition, TLR4 inhibition blocked GLE-mediated expressions of immunomodulators and activation of p38, JNK and NF-κB. Taken together, these results demonstrated that TLR4-MAPK/NF-κB signalling pathways participated in GLE-induced macrophage activation and GLE could be developed as a potential immunomodulating functional food.

본 논문은 포유동물 난소에서의 신속한 프로게스테론(P4) 선호 전달경로에 관해 현재 통용되는 지식을 요약하였다. P4는 안드로겐과 에스트로겐 합성 과정에서의 중요한 중간 산물이면서 그 자체로도 배란, 난포폐쇄(atresia), 황체형성과정(luteinization)에서 결정적인 역할을 하며, 모든 포유동물의 초기 임신 유지에 필수적이다. 이와 같은 생리적인 중요성에도 불구하고 포유동물 난소에서의 정확한 P4 작용기작은 아직까지도 완전히 알려져 있지 않다