Isothiocyanates as Novel Cancer Chemopreventive Agents and Their Underlying Molecular Mechanisms

A promising group of compounds that have a chemopreventive property are isothiocyanates (ITCs). ITCs have been shown to induce apoptosi in various cancer cell lines and experimental rodents. Multiple signaltransduction pathways as well as apoptosis intermediates have been also posturalted. We recently clarified the moleculae mechanism underlying the relationship between cell cycle arrest ad apoptosis induced by benzyl isothiocyanate(BITC), a major ITC compound isolated from papaya. The exposure of cells to BITC resulted in the inhibition of the G2/M progression that coincided with not only hte up-regulated expression of the G2/M cell cycle arrest-regulating genes but also the apoptosis induction. Conversely, treatment with an excessive concentration of BITC resulted in an abortive apoptotic pathway without DNA ladder formation. This commentary will review the biological impact of cell death induction by BITC as well as other ITCs and the involved signal transduction pathways.野菜全般の摂取と健康状態に関する疫学的研究は，近年数多く報告されており，様々な疾患リスクの低減だけでなく，通常の健康状態に関しても野菜の有効・有用性が示唆されている．その一方で，食生活の欧米化の着実な進行から，肉食・魚介類の順調な消費の伸びに対し，野菜消費量が減少の一途を辿っている．特に，若年齢層を中心とした世代の野菜消費量の減少が顕著であり，生活習慣病の若年齢化との相関から，社会問題として注目を浴びつつある．例えば，野菜を十分に摂取出来れば所要量の確保が容易なビタミンである葉酸であるが，新生児の神経管閉鎖障害症の最近の増加から，妊娠初期の女性の摂取不足に厚生労働省が警鐘を鳴らしている．また，昨今の栄養・健康情報の氾濫とサプリメント（栄養補助食品，健康補助食品）市場の急激な成長により，サプリメントを利用しておけば普段の食生活はないがしろにしても構わないという風潮に歯止めがかからなくなっている．野菜の摂取を推奨していくためには，人の健康と野菜摂取との関連を科学的かつ体系的に解明・整理にすることが今一度必要である．野菜中に含まれる，より具体的な機能性成分の性質や分布を正確に理解し，健康維持や疾病予防への寄与を明らかにすることができれば，より健全な「日本型食生活」への回帰を目指した野菜の消費拡大の一助となることはいうまでもない．それゆえ，これからの食品機能の基盤的研究が果たす役割は極めて重要であるといえる．食品機能の基盤的研究のなかで，現在最も体系的に進んでいる研究分野として，がん予防に関する研究が挙げられる．発がんの原因物質の排除と発がん抑制物質の積極的な摂取が「がんの化学予防」の基本戦略であるが，数多くの疫学的研究や動物実験の成果から，野菜や果物などの植物性食品の摂取が予防に有効であるといわれて久しい．特に，1990年代に米国で「デザイナーフーズ」計画がスタートしたことをきっかけとして，十数余年にわたるこれまでの研究は，がん予防に有望な素材・成分の化学的解明，動物実験成績や基本的作用機構に関する知見の蓄積だけでなく，その他の疾病をターゲットとし た食品機能研究の進展に大きく寄与してきた．その一方で，β-カロテンのヒト介入試験での不成功から，食品成分による疾病予防法確立への道は決して平坦なものではないことも浮彫りとなった．現在，がんの化学予防研究は，ヒトにおける有効性をどのように評価して行くかを共通課題とし，体内動態や遺伝子発現の網羅的，体系的解析などのより詳細な分子レベルでの研究へと進展を遂げつつあり，筆者も例に漏れず研究標的をシフトしてきた．また，これまで有効とされてきた素材・成分の再評価，品種改良などによる有効成分（活性及び含量の）増強素材の開発，より偏りの少ない食事・栄養指導など，網羅すべき課題の広がりにより，食品化学分野は新展開の局面を迎えてい

Lifelong Change Detection: Continuous Domain Adaptation for Small Object Change Detection in Every Robot Navigation

The recently emerging research area in robotics, ground view change detection, suffers from its ill-posed-ness because of visual uncertainty combined with complex nonlinear perspective projection. To regularize the ill-posed-ness, the commonly applied supervised learning methods (e.g., CSCD-Net) rely on manually annotated high-quality object-class-specific priors. In this work, we consider general application domains where no manual annotation is available and present a fully self-supervised approach. The present approach adopts the powerful and versatile idea that object changes detected during everyday robot navigation can be reused as additional priors to improve future change detection tasks. Furthermore, a robustified framework is implemented and verified experimentally in a new challenging practical application scenario: ground-view small object change detection

The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis

Dihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mM did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mM inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mM inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mM increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG

Fingering behavior of flame spread over solid combustibles

In this study, the fingering pattern formation and the following flamelet spreading over three different kinds of thick combustibles, i.e., Poly methacrylate (PMMA), Poly ethylene (PE) and Poly carbonate (PC) were observed and the effective Lewis number correlation was validated. Experiments were performed with a narrow channel apparatus. In addition to the kinds of solid fuel materials, the channel height and the oxidizer velocity were varied as experimental parameters. An image analysis method was developed to quantify the number, diameter and spread rate of the flamelets. Replacing the fuel thickness into the thermal thickness, the effective Lewis number which is proposed for the smoldering combustion of thin fuel is remedied to include heat transfer perpendicular to the fuel surface. The result validates that the appearance condition of the fingering instability for thick combustibles is determined by the effective Lewis number. Hence, it is concluded that the observed phenomenon is inherently similar to that of smoldering. Further, it is shown that the non-dimensional flame diameter becomes nearly constant when the fingering instability occurs. It is believed that the correlation is useful when one wants to reproduce this phenomenon in a larger scale experiment

Aromatic oil from lavender as an atopic dermatitis suppressant

In atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines

Synthesis and characterization of conductive flexible cellulose carbon nanohorn sheets for human tissue applications

Background Conductive sheets of cellulose and carbon nanomaterials and its human skin applications are an interesting research aspect as they have potential for applications for skin compatibility. Hence it is needed to explore the effects and shed light on these applications. Method To fabricate wearable, portable, flexible, lightweight, inexpensive, and biocompatible composite materials, carbon nanohorns (CNHs) and hydroxyethylcellulose (HEC) were used as precursors to prepare CNH-HEC (Cnh-cel) composite sheets. Cnh-cel sheets were prepared with different loading concentrations of CNHs (10, 20 50,100mg) in 200mg cellulose. To fabricate the bio-compatible sheets, a pristine composite of CNHs and HEC was prepared without any pretreatment of the materials. Results The obtained sheets possess a conductivity of 1.83x10(-10)S/m and bio-compatible with human skin. Analysis for skin-compatibility was performed for Cnh-cel sheets by h-CLAT in vitro skin sensitization tests to evaluate the activation of THP-1 cells. It was found that THP-1 cells were not activated by Cnh-cel; hence Cnh-cel is a safe biomaterial for human skin. It was also found that the composite allowed only a maximum loading of 100mg to retain the consistent geometry of free-standing sheets of m thickness. Since CNHs have a unique arrangement of aggregates (dahlia structure), the composite is homogeneous, as verified by transmission electron microscopy (TEM) and, scanning electron microscopy (SEM), and other functional properties investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), conductivity measurement, tensile strength measurement, and skin sensitization. Conclusion It can be concluded that cellulose and CNHs sheets are conductive and compatible to human skin applications

Tyrosine Phosphorylation Regulates the Expression of Major Histocompatibility Complex Antigens on a Human Lung Cancer Cell Line by Interferon-gamma

Expression of major histocompatibility complex (MHC) antigens on cancer cells is essential for cell-mediated immune function. However, these molecules are reduced on cancer cells enabling them to escape from host immune surveillance. It is well known that interferon-γ (IFN-γ) upregulates the expression of MHC molecules and restores the immunogenicity of cancer cells. Nevertheless, the mechanism by which IFN-γ modulates MHC expression on cancer cells is not clear. Therefore, in this report, we examined the role of tyrosine protein kinases in IFN-γ-induced MHC expression in a human lung adenocarcinoma cell line, HLC-1. We found that a tyrosine protein kinase inhibitor, herbimycin A, inhibited both IFN-γ-inducible MHC class I and class II expression, as assessed by flow cytometry. Additionally, assessment of tyrosine phosphorylation of cellular substrates by confocal laser microscopy using an anti-phosphotyrosine monoclonal antibody (mAb) revealed that IFN-γ induced protein tyrosine phosphorylation within 5 min of treatment. Herbimycin A inhibited this IFN-γ-induced tyrosine phosphorylation. Thus, tyrosine phosphorylation plays an important role in IFN-γ-induced MHC class I and class II expression on HLC-1 cells