Insect growth depends on temperature and nutrient. Intake nutrients activate insulin signaling pathway, which mediatesthe nutrient signal to coordinate growth in entire body. A subtropical species, Maruca vitrata (Lepidoptera: Crambidae),gives serious damages on various Fabaceae crops. This study predicted seven components (InR, IRS, PI3K, PTEN, Akt,mTOR, FOXO) of the insulin signal and showed that some of the insulin gene expression levels are highly correlatedwith developmental rates. These correlations may be applied to amend a temperature-dependent growth modeling of M.vitrata.

Aloe-emodin (AE) is the major bioactive component in aloe and known to exhibit anti-inflammatory activities. However, it has not been elucidated whether its anti-inflammatory potency can contribute to the elimination of obesity. The aim of the current study is to investigate the effect of AE on toll-like receptor 4 (TLR4) pathways in the presence of lipopolysaccharide (LPS) in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with AE (0-20 μM) for one hour, followed by LPS treatment for 30 min and then, adipokine mRNA expression levels were measured. Next, TLR4-related molecules were measured in LPS-stimulated 3T3-L1 adipocytes. AE significantly decreased the mRNA expression of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in a dose-dependent manner. Moreover, AE suppressed TLR4 mRNA expression. Further study showed that AE could suppress the nuclear factor-κB (NF-κB) and phosphorylation of extracellular receptor-activated kinase (pERK). The results of this study suggest that AE directly inhibits TLR4/NF-κB/ERK signaling pathways and decreases the inflammatory response in adipocytes.

Colony collapse disorder (CCD), a phenomenon of honeybees disappearance, has been reported since 2006. Chronic exposure to neonicotinoid insecticides, particularly imidacloprid, has been suggested to impair forager’s ability for foraging and be a main cause of CCD. Recently, it has been reported that imidacloprid induces insulin resistance in animal cell line by blocking glucose uptake. Similarly to human insulin, insulin-like peptide (ILP) of insects is involved in maintaining blood glucose contents in hemolymph by regulating the concentration of trehalose and glycogen. Therefore, we have hypothesized that sublethal concentration of neonicotinoid may affect the metabolic pathway of honey bees as well. We investigated the transcription levels of the genes involved in the insulin/insulin-like signaling (IIS) pathway, such as AmILP and AmInR, following an acute or a chronic dietary exposure of sublethal concentrations of imidacloprid to foragers. In both experiments, honeybees showed increased expression levels of ILP and InR in a dose-dependent manner. Our results suggest that sublethal dose of imidacloprid likely upregulates IIS pathway, thereby rendering honey bees to become resistant to insulin.

Oral lichen planus (OLP) is an atypically keratinized and ulcerative lesion, producing severe pain and discomforts in the involved patients. Nevertheless, the etiological factor or the pathogenetic mechanism has not been clearly elucidated. In the present study, the different gene expressions were screened in 21 cases of OLP by immunohistochemical (IHC) array method using 80 antibodies, and found that the pathway of E-cadherin/β-catenin was abnormally expressed compared to the other essential genetic pathways. Particularly, the expressions of eIF5A, DHS, and DOHH, which are the biomarkers of protein translation, were remarkably reduced, nevertheless the expression of β-catenin was strongly positive in the 7 cases among 21 cases of OLP. The other expressions of p53, BCL-2, MDM-2, PAKT, BAX, BAK, BAD, NFkB, HO-1, etc, were usually weak or sparse, while the expressions of PCNA, CDK4, and HSP-70 were markedly increased. Taken together, it is presumed that the overexpression of β-catenin indicates the derangement of E-cad/β-catenin/NFkB pathway, causing the transcription of cellular proliferating genes in downstream events, i.e., PCNA and CDK4, and that it may be eventually relevant to the malignant potential of OLP epithelial cells. It is also suggested that the activation of β-catenin/TCF/LEF1 pathway be closely relevant to the immunological reaction of OLP with the accumulation of T-cells underneath the mucosal epithelium.

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.

본 연구에서 상동나무 가지 추출물(STB-E100)은 대장암 세포에서 세포사멸을 유도하여 세포생육을 억제하였다. 또한 Iκ B-α 인산화를 통한 IκB-α 단백질 분해를 유도하며 이로 인해 P65 핵내 전이를 유도하여 NF-κB 신호전달을 활성화시킨다. NF-κB 신호전달 활성화는 GSK3β 활성화를 통해 P65 핵내 전 이를 유도에 의한 것이지만 IκB-α분해는 GSK3β 의존성이 아니다. 상동나무 가지 추출물은 이러한 신호전달 활성화를 통해 세포사멸을 유도하여 대장암의 세포생육을 억제한다. 본 결과를 바탕으로 상동나무 가지가 암 예방 및 치료를 목적으로한 표적 요법에서 항암제 개발의 잠재적 활용 소재로서 이용 가능하다고 사료된다. 그러나 대장암 세포에서 상동나무 가지 추출물에 의해 유도된 NF-κB 신호전달 작용기전을 좀 더 구체적으로 구명할 필요가 있고 대장암에 대한 세포사멸과 작용기전의 정확한 관련성을 조사하기 위해 추가적인 연구가 필요하다.

Long-term ultraviolet (UV) exposure accelerates the phenomenon of skin photo-aging by activating collagenase and elastase. In this study, we aimed to investigate the effects of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-irradiated damage in HaCaT cells and dorsal mouse skin. In HaCaT cells, cG&Re recovered UVB-reduced cell viability and inhibited protein expression of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (p-Erk), c-Jun N-terminal kinases (p-JNK), and a class of MAPKs (p-P38). Also, cG&Re suppressed UVB-induced collagen and elastin degradation by decreasing matrix metalloproteinases (MMPs) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) expression, which is a transcription factor. Similar results were observed in dorsal mouse skin. Taken together, our data indicate that cG&Re prevent UVB-induced skin photo-aging due to collagen/elastin degradation via activation of MAPKs, MMPs, and the NF-κB signaling pathway in vitro and in vivo.

Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of IL-1β, IL-6 and TNF-α as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated IκB-α degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of NF-κB activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, TNF-α, IL-6, IL-1β and MCP-1 via interruption of the NF-κB and MAPK/ATF2 signaling pathways.

The initial segment (IS) in rodents is functionally and structurally distinct from other epididymal segments and plays an important role in sperm maturation. We previously showed that, in the mouse epididymis, basal cells (BCs) extend a narrow luminal-reaching projection only in the IS, while in all other regions, they mainly nestle at the base of the epithelium. We also found that BC projections are regulated by testicular luminal factors, and the present study was aimed at characterizing the signaling pathway involved in their formation and elongation. Previous studies reported that testicular luminal factors maintain the extracellular signal-regulated kinase (ERK) in a highly phosphorylated state in the IS. We report here that the BC projections, which we call axiopodia, periodically extend and retract over time. We found that axiopodia extensions and retractions follow an oscillatory pattern. This movement is controlled by MAPK/ERK signaling pathway. Our results suggest that ERK phosphorylation plays a key role in the formation and elongation of BC projections. Such unexpected cell motility may reflect a novel mechanism by which specialized epithelial cells sample the luminal environment.