The Role of a Development Agency in Peacebuilding: Track One-and-a-Half Mediation in Mindanao

Japans development assistance to conflict-affected areas in Mindanao, southern Philippines, opened new pathways for the Japan International Cooperation Agency (JICA) to support multilateral peacebuilding efforts. JICA, in collaboration with Universiti Sains Malaysia, organized a series of Consolidation for Peace Seminars as Track One-and-a-Half mediations. Two aspects of Japans assistance to Mindanao enabled JICA to engage in peacemaking. First, Japans assistance to Mindanao formed a unique tripartite cooperation mechanism consisting of the International Monitoring Team, Mindanao Task Force, and Japan-Bangsamoro Initiative for Reconstruction and Development. JICA took part in all three modes of assistance. Second, providing assistance under a volatile cease-fire agreement in Mindanao motivated JICA to become involved in peacemaking outside the traditional function of development assistance

MFG-E8 Regulates Angiogenesis in Cutaneous Wound Healing

Our research group recently demonstrated that pericytes are major sources of the secreted glycoprotein and integrin ligand lactadherin (MFG-E8) in B16 melanoma tumors, and that MFG-E8 promotes angiogenesis via enhanced PDGF–PDGFRβ signaling mediated by integrin–growth factor receptor crosstalk. However, sources of MFG-E8 and its possible roles in skin physiology are not well characterized. The objective of this study was to characterize the involvement of MFG-E8 in skin wound healing. In the dermis of normal murine and human skin, accumulations of MFG-E8 were found around CD31+ blood vessels, and MFG-E8 colocalized with PDGFRβ+, αSMA+, and NG2+ pericytes. MFG-E8 protein and mRNA levels were elevated in the dermis during full-thickness wound healing in mice. MFG-E8 was diffusely present in granulation tissue and was localized around blood vessels. Wound healing was delayed in MFG-E8 knockout mice, compared with the wild type, and myofibroblast and vessel numbers in wound areas were significantly reduced in knockout mice. Inhibition of MFG-E8 production with siRNA attenuated the formation of capillary-like structures in vitro. Expression of MFG-E8 in fibrous human granulation tissue with scant blood vessels was less than that in granulation tissue with many blood vessels. These findings suggest that MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis

Theoretical Studies for Molecular Modeling of New Camptothecin Analogues

Irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino carbonyloxycamptothecin: CPT-11) is a widely used potent antitumor drug that is developed based on camptothecin. However, overexpression of ABCG2 (BCRP/MXR/ABCP) confers cancer cells resistance to SN-38, that is, the active metabolite of irinotecan. In the present study to develop a platform for the molecular modeling to circumvent cancer drug resistance associated with ABCG2, we have characterized a total of fourteen new SN-38 analogues by some typical properties, which were evaluated by molecular orbital (MO) calculations and neural network (NN) QSAR technique

Low intensity pulsed ultrasound exposure increases prostaglandin E_2 release in human dermal fibroblasts

Though ultrasound is applied to the treatment of pressure ulcers, there was little evidence of benefit associated with the use of it in the treatment of pressure ulcers. Therefore, in order to augment the therapeutic evidence of ultrasound exposure in wound healing, the effect of low intensity pulsed-ultrasound on the release of prostaglandin E_2 (PGE_2) in human dermal fibroblasts was investigated. Human dermal fibroblasts obtained from skin samples were exposed to a low intensity pulsed-ultrasound by specifically designed apparatus. An enzyme-linked immunosorbent assay determined the release of PGE_2 in the medium. A low intensity pulsed-ultrasound increases the PGE_2 release of dermal fibroblasts in a time-de-pendent fashion. PGE_2 release by 30 mW/cm^2 ultrasound exposure reached maximum 1.24-fold at 1 hour. In terms of the intensities of ultrasound, the weaker intensity of ultrasound was exposed, the more effect of PGE_2 release was observed. Finally, a specific inhibitor of cyclooxygenase-1, resveratrol partly reduced PGE_2 release of dermal fibroblasts by ultrasound exposure. Thus, our results identify the effect of low intensity pulsed ultrasound to explain the potential mechanism by which it may augment the healing of skin ulcer. Further studies are required to ascertain the functional relevance of the production of PGE_2 in angiogenesis, which is required for the tissue development and regeneration

Real-time In Situ Electron Spin Resonance Measurements on Fungal Spores of Penicillium digitatum during Exposure of Oxygen Plasmas

We report the kinetic analysis of free radicals on fungal spores of Penicillium digitatum interacted with atomic oxygen generated plasma electric discharge using real time in situ electron spin resonance (ESR) measurements. We have obtained information that the ESR signal from the spores was observed and preliminarily assignable to semiquinone radical with a g-value of around 2.004 and a line width of approximately 5G. The decay of the signal is possibly linked to the inactivation of the fungal spore. The real-time in situ ESR has proven to be a useful method to elucidate plasma-induced surface reactions on biological specimens.Comment: 11 pages, 5 figure

Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism.

Low body temperature predicts a poor outcome in patients with heart failure, but the underlying pathological mechanisms and implications are largely unknown. Brown adipose tissue (BAT) was initially characterised as a thermogenic organ, and recent studies have suggested it plays a crucial role in maintaining systemic metabolic health. While these reports suggest a potential link between BAT and heart failure, the potential role of BAT dysfunction in heart failure has not been investigated. Here, we demonstrate that alteration of BAT function contributes to development of heart failure through disorientation in choline metabolism. Thoracic aortic constriction (TAC) or myocardial infarction (MI) reduced the thermogenic capacity of BAT in mice, leading to significant reduction of body temperature with cold exposure. BAT became hypoxic with TAC or MI, and hypoxic stress induced apoptosis of brown adipocytes. Enhancement of BAT function improved thermogenesis and cardiac function in TAC mice. Conversely, systolic function was impaired in a mouse model of genetic BAT dysfunction, in association with a low survival rate after TAC. Metabolomic analysis showed that reduced BAT thermogenesis was associated with elevation of plasma trimethylamine N-oxide (TMAO) levels. Administration of TMAO to mice led to significant reduction of phosphocreatine and ATP levels in cardiac tissue via suppression of mitochondrial complex IV activity. Genetic or pharmacological inhibition of flavin-containing monooxygenase reduced the plasma TMAO level in mice, and improved cardiac dysfunction in animals with left ventricular pressure overload. In patients with dilated cardiomyopathy, body temperature was low along with elevation of plasma choline and TMAO levels. These results suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.We thank Kaori Yoshida, Keiko Uchiyama, Satomi Kawai, Naomi Hatanaka, Yoko Sawaguchi, Runa Washio, Takako Ichihashi, Nanako Koike, Keiko Uchiyama, Masaaki Nameta (Niigata University), Kaori Igarashi, Kaori Saitoh, Keiko Endo, Hiroko Maki, Ayano Ueno, Maki Ohishi, Sanae Yamanaka, Noriko Kagata (Keio University) for their excellent technical assistance, C. Ronald Kahn (Joslin Diabetes Center and Harvard Medical School) for providing the BAT cell line, Evan Rosen (Harvard Medical School) for providing us Ucp-Cre mice, Kosuke Morikawa (Kyoto University), Tomitake Tsukihara (University of Hyogo) and Shinya Yoshikawa (University of Hyogo) for their professional opinions and suggestions. Tis work was supported by a Grant-in-Aid for Scientifc Research (A) (20H00533) from MEXT, AMED under Grant Numbers JP20ek0210114, and AMED-CREST under Grant Number JP20gm1110012, and Moonshot Research and Development Program (21zf0127003s0201), MEXT Supported Program for the Strategic Research Foundation at Private Universities Japan, Private University Research Branding Project, and Leading Initiative for Excellent Young Researchers, and grants from the Takeda Medical Research Foundation, the Vehicle Racing Commemorative Foundation, Ono Medical Research Foundation, and the Suzuken Memorial Foundation (to T.M.). Support was also provided by a Grants-in-Aid for Young Scientists (Start-up) (26893080), and grants from the Uehara Memorial Foundation, Kowa Life Science Foundation, Manpei Suzuki Diabetes Foundation, SENSHIN Medical Research Foundation, ONO Medical Research Foundation, Tsukada Grant for Niigata University Medical Research, Te Nakajima Foundation, SUZUKEN memorial foundation, HOKUTO Corporation, Mochida Memorial Foundation for Medical & Pharmaceutical Research, Grants-in-Aid for Encouragement of Young Scientists (A) (16H06244), Daiichi Sankyo Foundation of Life Science, AMED Project for Elucidating and Controlling Mechanisms of Aging and Longevity under Grant Number JP17gm5010002, JP18gm5010002, JP19gm5010002, JP20gm5010002, JP21gm5010002, Astellas Foundation for Research on Metabolic Disorders, Research grant from Naito Foundation, Te Japan Geriatrics Society (to I.S.); by a Grant-in-Aid for Scientifc Research (C) (19K08974), Yujin Memorial Grant, Sakakibara Memorial Research Grant from Te Japan Research Promotion Society for Cardiovascular Diseases, TERUMO Life Science Foundation, Kanae Foundation (to Y.Y.), JST ERATO (JPMJER1902), AMED-CREST (JP20gm1010009), the Takeda Science Foundation, the Food Science Institute Foundation (to S.F.), and by a grant from Bourbon (to T.M., I.S. and Y.Y.).S