A novel S-sulfhydrated human serum albumin preparation suppresses melanin synthesis

Products of ultraviolet (UV) irradiation such as reactive oxygen species (ROS) and nitric oxide (NO) stimulate melanin synthesis. Reactive sulfur species (RSS) have been shown to have strong ROS and NO scavenging effects. However, the instability and low retention of RSS limit their use as inhibitors of melanin synthesis. The free thiol at Cys34 on human serum albumin (HSA) is highly stable, has a long retention and possess a high reactivity for RSS. We report herein on the development of an HSA based RSS delivery system. Sulfane sulfur derivatives released from sodium polysulfides (Na2Sn) react readily with HSA. An assay for estimating the elimination of sulfide from polysulfide showed that almost all of the sulfur released from Na2Sn bound to HSA. The Na2Sn-treated HSA was found to efficiently scavenge ROS and NO produced from chemical reagents. The Na2Sn-treated HSA was also found to inhibit melanin synthesis in B16 melanoma cells and this inhibition was independent of the number of added sulfur atoms. In B16 melanoma cells, the Na2Sn-treated HSA also inhibited the levels of ROS and NO induced by UV radiation. Finally, the Na2Sn-treated HSA inhibited melanin synthesis from L-DOPA and mushroom tyrosinase and suppressed the extent of aggregation of melanin pigments. These data suggest that Na2Sn-treated HSA inhibits tyrosinase activity for melanin synthesis via two pathways; by directly inhibiting ROS signaling and by scavenging NO. These findings indicate that Na2Sn-treated HSA has potential to be an attractive and effective candidate for use as a skin whitening agent

Roles of Macrophages in Advanced Liver Fibrosis, Identified Using a Newly Established Mouse Model of Diet-Induced Non-Alcoholic Steatohepatitis

Macrophages play critical roles in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is unclear which macrophage subsets are critically involved in the development of inflammation and fibrosis in NASH. In TSNO mice fed a high-fat/cholesterol/cholate-based diet, which exhibit advanced liver fibrosis that mimics human NASH, we found that Kupffer cells (KCs) were less abundant and recruited macrophages were more abundant, forming hepatic crown-like structures (hCLS) in the liver. The recruited macrophages comprised two subsets: CD11c+/Ly6C−and CD11c− /Ly6C+ cells. CD11c+ cells were present in a mesh-like pattern around the lipid droplets, constituting the hCLS. In addition, CD11c+ cells colocalized with collagen fibers, suggesting that this subset of recruited macrophages might promote advanced liver fibrosis. In contrast, Ly6C+cells were present in doughnut-like inflammatory lesions, with a lipid droplet in the center. Finally, RNA sequence analysis indicates that CD11c+/Ly6C− cells promote liver fibrosis and hepatic stellate cell (HSC) activation, whereas CD11c−/Ly6C+ cells are a macrophage subset that play an anti-inflammatory role and promote tissue repair in NASH. Taken together, our data revealed changes in liver macrophage subsets during the development of NASH and shed light on the roles of the recruited macrophages in the pathogenesis of advanced fibrosis in NASH

Community Clinical Psychological Support of an Evening High School (IV) : providing the revised model of support activities

ある定時制高校の支援要請に対する地域臨床的な支援活動も、筆者らで4年目を迎えた。今年度の支援活動は、昨年度の報告で提示された「支援モデル」（山見・細見・吉川ら，2013）を引き継ぐ形で活動方針を立て、さらに中島・津田・中條ら（2013）が挙げた「今後の課題」を受け、さまざまな改良・改善を加えた。今年度は、昨年度同様、校内支援委員会の開催やグループワークの実施など、定時制高校の先生方との関係性を維持することができた。また、校内巡回や学校行事などへの参加によって、今まで以上に生徒や先生方とのつながりを感じる機会も多かった1年である。そこで、本稿ではまず今年度の支援活動経過を活動内容別に項目立てて報告する。次に、その報告を「支援モデル」の6つの構成要素別に考察する。そして最後に、各構成要素を抽出・羅列するにとどまっていた昨年度の「支援モデル」に対して、各構成要素の関係性や位置関係を明らかにし、新たな改訂版支援モデルとして提示する。For the past three years, the authors have been continuing to provide psychological support to an evening high school. We formed our support activity schemes based on an initial support model (Yamami, Hosomi, Yoshikawa et al., 2013) . Over the year, we gradually made some additions and improvements to that model, taking into consideration the future tasks suggested by Nakajima, Tsuda, Chujo et al. (2013) . We feel that the relationship with the teachers was strengthened through continuous contact and more involvement in school events. The purpose of this article is threefold. First, we report on details of our support activities. Second, we discuss them from the viewpoint of each of the six elements of the support model (Yamami, Hosomi, Yoshikawa et al., 2013) . Finally, we clarify the relationship between the elements of the model, and provide a revised version

Poster Session: Abstracts

The 3rd International Symposium on Carcinogenic Spiral & International Symposium on Tumor Biology in Kanazawa, [DATE]: January 24(Thu)-25(Fri),2013, [Place]:Kanazawa Excel Hotel Tpkyu, Kanazawa, Japan, [Organizers]:Infection/Inflammation-Assisted Acceleration of the Carcinogenic Spiral and its Alteration through Vector Conversion of the Host Response to Tumors / Scientific Research on Innovative Areas, a MEXT Grant-in Aid Projec

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

Therapeutic plasma exchange in postpartum HELLP syndrome: a case report

BackgroundPostpartum hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is more difficult to treat than HELLP syndrome during pregnancy. We describe a case of postpartum HELLP syndrome that responded to plasma exchange (PE) therapy.Case presentationA 30-year-old primipara woman was hospitalized for gestational hypertension at 33 weeks of gestation and underwent an emergent cesarean section at 36 weeks and 6 days of gestation due to rapidly progressing pulmonary edema. After delivery, liver dysfunction and a rapid decrease in platelet count were observed, and the patient was diagnosed with severe HELLP syndrome. She experienced multiple organ failure despite intensive care, and PE therapy was initiated. Her general condition dramatically stabilized within a few hours of PE therapy.ConclusionIt is controversial whether PE therapy should be used primarily in the management of HELLP syndrome, but early initiation of PE therapy could be effective for severe HELLP syndrome