Online harassment of Japanese celebrities and influencers.

Famous people, such as celebrities and influencers, are harassed online on a daily basis. Online harassment mentally disturbs them and negatively affects society. However, limited studies have been conducted on the online harassment victimization of famous people, and its effects remain unclear. We surveyed Japanese famous people (N = 213), who were influential people who appeared on television and other traditional media and on social media, regarding online harassment victimization, emotional injury, and action against offenders and revealed that various forms of online harassment are prevalent. Some victims used the anti-harassment functions provided by weblogs and social media systems (e.g., blocking/muting/reporting offender accounts and closing comment forms), talked about their victimization to close people, and contacted relevant authorities to take legal action (talent agencies, legal consultants, and police). By contrast, some victims felt compelled to accept harassment and did not initiate action for offenses. We propose several approaches to support victims, inhibit online harassment, and educate people. Our findings help that platforms establish support systems against online harassment.

RESULTS AND DISCUSSION ON JAPANESE PUBLIC OPINION SURVEYS (2006-17) ABOUT NUCLEAR AND RADIATION APPLICATIONS.

Public opinion on the application of nuclear technology and radiation could change when a nuclear related event occurs. Japan Atomic Energy Relations Organization has tracked its variation through a nationwide opinion survey in Japan by almost the same way every year since FY 2006. We can identify a continuous long-term fluctuation of Japanese opinion before and after the TEPCO Fukushima Daiichi nuclear disaster using the data. In this study we focused on the trends of public opinion for nuclear energy, impressions and knowledge on radiation, and zero-risk request. For example, radiation can be recognised that it is dangerous and complicated matter by Japanese public regardless of that accident. However, a big change of opinions on radiation was shown on the impression for the word of 'Useful' between before and after the accident.

A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.

Stromal cells in lymphoid tissues provide microenvironmental fields required for the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs) are one of the integral constituents of such stromal fields; they construct the reticular network and are considered to regulate immune cells' behavior. However, the factors that mediate the interaction between lymphocytes and FRCs are poorly understood. Here we show that a mouse lymph node (LN)-derived FRC cell line, BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in response to tumor necrosis factor alpha (TNFalpha) and IFNgamma. TNFalpha-induced expression of CXCL16 depends on NFkappaB, p38 MAPK and PKA. Matrix metalloproteinase activity is required for producing soluble CXCL16 in the culture supernatant, likely via shedding at the juxtamembrane region of the extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28-stimulated CD8+ T cells and their adhesion to the BLS4 cell surface in a TNFalpha-dependent fashion. The adherence is significantly inhibited in the presence of both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies. CXCL16 expression is also detected in the FRCs in LN sections and in gp38+VCAM-1+ FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an important mediator of lymphocyte-stromal interaction within lymphoid tissues.

Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression.

Pdx-1 plays important roles both in the development of the pancreas and in maintaining pancreatic beta cell function. However, the role of Pdx-1 in the regulation of insulin release is not well established. We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). Insulin secretion is regulated in vivo by the sequential events triggered by the increase of intracellular Ca(2+)-concentration in response to high glucose concentration. In the present study, we identified a new target of Pdx-1 involved in insulin release. Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus.

In vitro induction of adult hepatic progenitor cells into insulin-producing cells.

Organ-specific stem cells are the natural progenitors in tissue regeneration and possess plasticity to differentiate into specialized cells in adult tissues. Small hepatocytes (SHCs) identified in the adult liver are one such cell type. Here we show that SHCs, which are capable of self-renewal and differentiation into hepatocytes, can be induced to generate insulin-producing cells under appropriate culture conditions. These differentiated cells express pancreatic beta cell differentiation-related transcripts and hepatocyte differentiation-related transcripts, as shown by reverse-transcription PCR/nested PCR. In addition, enforced expression of the homeodomain transcription factor Pdx1 in these cells contributes to enhancement of insulin release in response to insulin secretagogues. These results indicate that the SHCs described here have the ability to differentiate into insulin-producing cells, and further support the idea that engineering to generate insulin-secreting cells could provide a useful resource for future therapies for diabetes mellitus.

The efficient prevascularization induced by fibroblast growth factor 2 with a collagen-coated device improves the cell survival of a bioartificial pancreas.

OBJECTIVES: The subcutaneous transplantation of a bioartificial pancreas is a very attractive cure for diabetes mellitus. We recently developed a new immunoisolatory device that has the ability to induce neovascularization for subcutaneous transplantation. We applied the newly developed device to subcutaneous transplantation of a bioartificial pancreas. METHODS: We investigated the prevascularization-inducing activity of the device in diabetic rats by histologic analysis and evaluated the permeability of the device to insulin and BSA. We also evaluated the survival of cells enclosed in a bioartificial pancreas, which was composed of the device, from the viewpoint of the effects of prevascularization by semiquantitative RT-PCR. RESULTS: The devices induced prevascularization more efficiently than fibroblast growth factor 2 impregnated in gelatin microspheres alone did and had more useful permeability than a noncollagen-coated device. Significantly higher expression of insulin mRNA was detected in the RT-PCR amplicons from cells retrieved from the bioartificial pancreas transplanted at the prevascularization-induced site as compared with at a nonprevascularization-induced site. CONCLUSION: We demonstrated that our newly developed device has a superior ability to induce prevascularization in diabetic rats, and the prevascularization improves the initial cell survival of the implanted cells following transplantation.

The development of new immunoisolatory devices possessing the ability to induce neovascularization.

The transplantation of a bioartificial pancreas has been regarded as a potential method for successful islet transplantation without any immunosuppressive agents. The subcutaneous site is a very attractive site for transplantation of a bioartificial pancreas because of its advantage of an easy operation site. Our group has been reporting that transplantation of a bioartificial pancreas to the subcutaneous site can reverse hyperglycemia in diabetic recipients. Regarding shapes of a bioartificial pancreas, it is believed that a bag form has an advantage because it is easy to prepare a large quantity. Our group previously reported successful transplantation of a bioartificial pancreas in bag form, a mesh-reinforced polyvinyl alcohol bag (MRPB), implanted in the peritoneal cavity. We also reported that the effect of subcutaneous islet transplantation can be greatly improved with prevascularization treatment. In the present study, we attempted to combine MRPB to our protocol of subcutaneous prevascularization. The main problem of this trial is that the procedure of MRPB implantation injures the prevascularized blood vessel networks. To solve this problem, we made a slight alternation in our protocol, and designed new devices on the basis of MRPB. The new devices, possessing the ability to induce neovascularization, were prepared by collagen coating on the surface of MRPB and were implanted with/without different doses of FGF-2 impregnated in gelatin microspheres. When using 5 microg of FGF-2, more blood vessels were observed on the surface of type I/IV collagen-coated MRPB compared with the original MRPB and type I collagen-coated MRPB. Quite a few blood vessels were observed either around the injection site of 50 microg of FGF-2 impregnated in gelatin microspheres alone or around the implantation site of FGF-2-free gelatin microspheres and type I collagen-coated MRPB or type I/IV collagen-coated MRPB. Here we demonstrated that the combination of both FGF-2 impregnated in gelatin microspheres and collagen-coated MRPB could give an effective system of neovascularization suitable for subcutaneous implantation of a bioartificial pancreas.

Bioartificial pancreas transplantation at prevascularized intermuscular space: effect of angiogenesis induction on islet survival.

INTRODUCTION: Bioartificial pancreas (BAP) transplantation offers a potential treatment of diabetes mellitus. The optimal site for BAP transplantation has not yet been established. AIM: To monitor the effect of induction of neovascularization at the intermuscular space on islet survival after allogenic transplantation of BAP. METHODOLOGY: Angiogenesis was induced at the intermuscular space of diabetic Lewis rats by implanting a polyethylene terephthalate (PET) mesh bag, which enclosed a collagen sponge and biodegradable gelatin microspheres containing basic fibroblast growth factor. After confirmation of angiogenesis, BAP was prepared by mixing of 5% agarose with approximately 2,800 isolated rat (Sprague-Dawley) islets and transplanted into the prevascularized PET mesh bag. RESULTS: Neovascularization was observed in and around the PET mesh bag within 10 days after implantation as confirmed by macroscopic and microscopic examinations. In the presence of a collagen sponge, new blood vessels penetrated into the PET mesh bag and formed a vascular bed. After transplantation, normoglycemia was achieved in the rats within 3 days and maintained for >35 days. The rats gradually gained body weight, and the results of intravenous glucose tolerance test showed normal patterns of blood glucose clearance 1 month after transplantation. CONCLUSION: It can be concluded that the prevascularized PET mesh bag enabled transplanted BAP to survive and maintain function, thus indicating a potential site for BAP transplantation.

Repairing of rabbit skull defect by dehydrothermally crosslinked collagen sponges incorporating transforming growth factor beta1.

Collagen sponges of various biodegradabilities were prepared by dehydrothermal crosslinking at 140 degrees C for different time periods. When the collagen sponges were radioiodinated and implanted subcutaneously into the back of mice, the radioactivity remaining at the implanted site decreased with time; the longer the time of dehydrothermal crosslinking, the slower the radioactivity decrement. The radioactivity following the subcutaneous implantation of collagen sponges incorporating (125)I-labeled transforming growth factor (TGF)-beta1 also decreased with time. The time profile of both the radioactivity remainings was in good accordance to each other, irrespective of the crosslinking time. This indicates that the TGF-beta1 incorporated in the sponges was released as a result of sponge biodegradation. Potential of collagen sponges incorporating 0.1 micro g of TGF-beta1 in repairing the defect of rabbit skulls was evaluated in a stress-unloaded state. Bone repairing was induced by application of the collagen sponges incorporating 0.1 micro g of TGF-beta1 whereas that of free TGF-beta1 at the same dose and TGF-beta1-free, empty collagen sponges were ineffective. The bone defect was histologically closed by the bone tissue newly formed 6 weeks after application. Bone mineral density (BMD) analysis revealed that the collagen sponge incorporating TGF-beta1 enhanced the BMD value at the bone defect to a significantly great extent compared with other agents. A maximum enhancement of BMD was observed for the collagen sponge incorporating TGF-beta1 which was prepared by dehydrothermal crosslinking for 6 h. It was concluded that the TGF-beta1 incorporated in the collagen sponge was released in a biologically active form as a result of sponge biodegradation, resulting in enhanced bone repairing at the skull defect. It is possible that for too slowly degraded sponges, the remaining physically impairs the bone repairing at the skull defect. Induction of bone repairing would not be achieved through a rapid release of TGF-beta1 from too fast-degraded sponge.

Reversal of diabetes in mice by xenotransplantation of a bioartificial pancreas in a prevascularized subcutaneous site.

BACKGROUND: The subcutaneous site has been regarded as a potential site for a bioartificial pancreas. Transplantation of islets, encapsulated by the development of diverse biocompatible materials and structural designs, can reverse hyperglycemia in diabetic recipients. METHODS: Approximately 750 Sprague-Dawley rat islets macroencapsulated in an agarose/poly (styrene sulfonic acid) mixed gel were implanted into a prevascularized subcutaneous site. The site was constructed by subcutaneous injection of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres in streptozotocin-induced C57BL/6 diabetic mice. Diabetic mice treated with bFGF-free gelatin microspheres and diabetic mice without any treatment undergoing the same subcutaneous transplantation were used as controls. After transplantation, non-fasting blood glucose, body weight, intraperitoneal glucose tolerance test, and histologic evaluations were processed. RESULTS: All the recipients undergoing the subcutaneous xenograft returned to normoglycemia within 1 week after transplantation. Eight of 10 recipients in the bFGF+ group maintained normoglycemia for a period of 38-101 days and gradually gained increase of body weight. Two of 10 recipients became hyperglycemic again when the grafts were respectively retrieved at days 31 and 63. Intraperitoneal glucose tolerance tests at month 1 and 2 revealed significant ameliorated glucose tolerance but a tendency to reduced glucose tolerance when compared respectively with those of the streptozotocin-induced diabetic mice and normal mice. Histologic examination revealed that islets within the retrieved grafts at days 31 and 63 were viable and intact; no fibrotic overgrowth was present around the surface of grafts. CONCLUSIONS: A successfully prevascularized subcutaneous site could be constructed by a tissue bioengineering approach. Xenotransplantation of the agarose/poly (styrene sulfonic acid) mixed gel-based bioartificial pancreas in the prevascularized subcutaneous site could reverse diabetes in mice.