RANKL-induced DC-STAMP is essential for osteoclastogenesis

Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor– B ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DCSTAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.Toshio Kukita, Naohisa Wada, Akiko Kukita, Takashi Kakimoto, Ferry Sandra, Kazuko Toh, Kengo Nagata, Tadahiko Iijima, Madoka Horiuchi, Hiromi Matsusaki, Kunio Hieshima, Osamu Yoshie and Hisayuki Nomiyam

Relationship between serum isoflavone concentrations and frequency of soybean products consumption in patients with prostate cancer

Dietary consumption of high concentrations of soybean products has been suggested to reduce the risk for prostate cancer (PCa). We conducted a survey using patients with PCa to assess the relationship between serum concentrations of isoflavone aglycones and frequency of soybean products consumption in patients with PCa. We measured the serum concentrations of daidzein, genistein, glycitein, and equol in 99 PCa patients, in addition to conducting a survey using a self administrated questionnaire that included the frequencies of various food item consumptions. If serum concentrations of equol were at a value less than 0.5 ng/mL, they were classified as an equol non producer, and the other patients were classified as equol producers. As a result, serum concentrations of daidzein, genistein, and glycitein were found to be significantly correlated to each other (P<0.001). The frequency of tofu (soybean curd) consumption was significantly correlated with the serum concentration of daidzein (P<0.05). Likewise, the frequency of natto (fermented soybean) consumption was significantly correlated with the serum concentrations of daidzein, genistein, and glycitein (P<0.01). In the study there were 40 equol producers and 59 equol non producers, but none of the food items were significantly different between the equol producers and the equol non producers. We have a plan to perform a similar survey for population based controls in the future. Comparisons between the data of the PCa patients and the controls would give us more information about the role of isoflavones and equol production in regard to the risk of PCa

AGEs increase IL-6 and ICAM-1 expression

Background and Objectives: Diabetes mellitus (DM) is a risk factor for periodontal diseases and may exacerbate the progression of the pathogenesis of periodontitis. Advanced glycation end-products (AGEs) cause DM complications relative to levels of glycemic control and larger amounts accumulate in the periodontal tissues of patients with periodontitis and DM. In the present study, we investigated the effects of AGEs on the expression of inflammation-related factors in human gingival fibroblasts (HGFs) in order to elucidate the impact of AGEs on DM-associated periodontitis. Materials and Methods: HGFs were cultured with or without AGEs. Cell viability was examined, and RNA and protein fractions were isolated from AGE-treated cells. The expression of IL-6, ICAM-1, and the receptor for AGE (RAGE) was investigated using RT-PCR, quantitative real-time PCR, and ELISA, and reactive oxygen species (ROS) activity was measured using a kit with 2’,7’-dichlorofluorescin diacetate. Human monocytic cells (THP-1) labelled with a fluorescent reagent were co-cultured with HGFs treated with AGEs and IL-6 siRNA, and the adhesive activity of THP-1 cells to HGFs was assessed. The expression of IL-6 and ICAM-1 was examined when HGFs were pretreated with recombinant human IL-6 (rhIL-6), the siRNAs of RAGE and IL-6, and inhibitors of MAPK and NF-κB, and then cultured with and without AGEs. The phosphorylation of MAPK and NF-κB was assessed using Western blotting. Results: AGEs increased the mRNA and protein expressions of RAGE, IL-6, ICAM-1 and ROS activity in HGFs, and promoted the adhesion of THP-1 cells to HGFs, but had no effect on cell viability until 72 h. rhIL-6 increased ICAM-1 expression in HGFs, while the siRNAs of RAGE and IL-6 inhibited AGE-induced IL6 and ICAM1 mRNA expression, and IL-6 siRNA depressed AGE-induced THP-1 cell adhesion. AGEs increased the phosphorylation of p38 and ERK MAPKs, p65 NF-κB, and IκBα, while inhibitors of p38, ERK MAPKs, and NF-κB significantly decreased AGE-induced IL-6 and ICAM-1 expression. Conclusions: AGEs increase IL-6 and ICAM-1 expression via the RAGE, MAPK and NF-κB pathways in HGFs and may exacerbate the progression of the pathogenesis of periodontal diseases

Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts.

Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis

The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase (<it>MMP</it>) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of <it>MMP-1 </it>and <it>MMP-3 </it>with susceptibility to oral squamous cell carcinoma (OSCC).</p> <p>Methods</p> <p>We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of <it>MMP-1 </it>and <it>MMP-3</it>.</p> <p>Results</p> <p>The frequency of the <it>MMP-1 </it>2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (<it>p </it>= 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47–4.14, <it>p </it>= 0.0006), and those carrying the <it>MMP-1 </it>2G allele had a 2.30-fold risk (95%CI 1.15–4.58, <it>p </it>= 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the <it>MMP-1 </it>1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.</p> <p>Conclusion</p> <p>Since the 2G allele is a majority of the <it>MMP-1 </it>genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the <it>MMP-1 </it>2G allele in the early onset OSCC.</p

Photonic quantum technologies

The first quantum technology, which harnesses uniquely quantum mechanical effects for its core operation, has arrived in the form of commercially available quantum key distribution systems that achieve enhanced security by encoding information in photons such that information gained by an eavesdropper can be detected. Anticipated future quantum technologies include large-scale secure networks, enhanced measurement and lithography, and quantum information processors, promising exponentially greater computation power for particular tasks. Photonics is destined for a central role in such technologies owing to the need for high-speed transmission and the outstanding low-noise properties of photons. These technologies may use single photons or quantum states of bright laser beams, or both, and will undoubtably apply and drive state-of-the-art developments in photonics

ナイチンゲール病棟の設計思想とプライバシー ―時代背景にみるプライバシーの捉え方－

【要旨】著者らは，看護学生を対象にナイチンゲールが考案したナイチンゲール病棟に関するイメージ調査を行った結果，患者のプライバシー確保に関して否定的な回答がみられた．そこでナイチンゲールがプライバシーをどのように捉えているかを，ナイチンゲール著作集で確認すると，看護師側のプライバシーについてのみ記述され，患者側のプライバシーを守ることについての記述はなかった．そこで，ナイチンゲール病棟が提唱された 1860 年代からの英国文学作品 6 作品を用い，羞恥心への認識と，質問紙により現代の看護学生が感じる羞恥心レベルについて調査し，ナイチンゲール病棟の設計 思想と現代におけるプライバシーの捉え方について検討した．文献検討では，その時代前後で，病院の患者の階級や求められる医療が変化し，プライバシーが必要になった．ナイチンゲール病棟を提唱した時期はちょうどその過渡期であり，プライバシーへの十分な配慮がなされていなかったことが示唆された．看護学生のアンケート調査では，患者が治療を受ける場合，特に身体の一部が露出されるときに羞恥心が あると答えていた．ナイチンゲール病棟については，看護者の目が行き届き安心感を与えるが，患者のプラ イバシーがないと捉えていた．Abstract: We administered a questionnaire survey of a hospital ward designed by Florence Nightingale called “Nightingale ward” to nursing students, and obtained negative responses regarding securing patient privacy. Given the results above, we reviewed Nightingale’s publications to learn her perspective on privacy. Our review showed that privacy was described only from the standpoint of nurses and there was no reference to patient privacy protection. In order to investigate privacy issues with the Nightingale ward, we reviewed six British literary works published during the 1860s, the period in which the Nightingale ward was proposed, to investigate how people at that time thought about embarrassment, and surveyed the extent of patients’ embarrassment that was perceived by the present-day nursing students. Literature review showed that the social classes of inpatients and required medical care changed around the period of time in which Nightingale lived, leading to increased significance of privacy protection. The time when the Nightingale ward was proposed was exactly in the transition stage, and privacy had not been given adequate attention. According to the survey results, the nursing students felt that patients were embarrassed during treatment, especially when parts of their body were exposed. Openness of the Nightingale ward may bring a sense of ease for patients but it also poses difficulty in securing their privacy. The results indicated that this issue may be a potential factor to make patients feel embarrassed, and the Nightingale ward was therefore considered to “lack privacy.