Country：Japan

Country：Japan

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Factors affecting the probability of hepatocellular carcinoma (HCC) development even after sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remain unelucidated. This study characterized the role of 16 soluble (s) immune checkpoint proteins in 168 HCV-SVR patients, with 47 developing HCC at the study end point. At baseline, high concentrations of 10 immune checkpoint proteins were found in the sera of the HCC group. At the study end point, levels of sCD27, sCD28, sCD40, and sCD86 in the HCC group, which were depleted following SVR, returned to higher levels than those in the non-HCC group. More importantly, patients with baseline levels of sCD27 ≥ 4104 pg/mL, sCD28 ≥ 1530 pg/mL, and sCD40 ≥ 688 pg/mL predicted a significantly greater HCC cumulative rate. Although sCD27 was elevated in patient sera, its membrane-bound form, mCD27, accumulated in the tumor and peritumor area, mainly localized in T cells. Interestingly, T-cell activation time dependently induced sCD27. Furthermore, CD70, the ligand of CD27, was robustly expressed in HCC area in which CD70 promoter methylation analysis indicated the hypomethylation compared with the nontumor pairs. Recombinant human CD27 treatment induced the proliferation of CD70-bearing HepG2 cells via the mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase pathway, but not NF-κB or p38 pathway. In conclusion, these data indicate that baseline sCD27, sCD28, and sCD40 levels could be used as HCC prognostic markers in HCV-SVR patients. sCD27 likely promotes HepG2 cell growth via the CD27-CD70 axis.

DOI： 10.1016/j.ajpath.2022.07.003

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver.

DOI： 10.1126/sciadv.abo5525

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ajpath.2020.12.007

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Hepatic stellate cells (HSCs) are resident mesenchymal cells in the space of Disse interposed between liver sinusoidal endothelial cells and hepatocytes. Thorn-like microprojections, or spines, project out from the cell surface of HSCs, crossing the space of Disse, to establish adherens junctions with neighboring hepatocytes. Although HSC activation is initiated largely from stimulation by adjacent cells, isolated HSCs also activate spontaneously in primary culture on plastic. Therefore, other unknown HSC-initiating factors apart from paracrine stimuli may promote activation. The dissociation of adherens junctions between HSCs and hepatocytes as an activating signal for HSCs was explored, establishing epithelial cadherin (E-cadherin) as an adhesion molecule linking hepatocytes and HSCs. In vivo, following carbon tetrachloride-induced liver injury, HSCs lost their spines and dissociated from adherens junctions in the early stages of injury, and were subsequently activated along with an increase in YAP/TAZ expression. After abrogation of liver injury, HSCs reconstructed their spines and adherens junctions. In vitro, reconstitution of E-cadherin-containing adherens junctions by forced E-cadherin expression quiesced HSCs and suppressed TAZ expression. Additionally, increase of TAZ expression leading to the activation of HSCs by autocrine stimulation of transforming growth factor-β, was revealed as a mechanism of spontaneous activation. Thus, we have uncovered a critical event required for HSC activation through enhanced TAZ-mediated mechanotransduction after the loss of adherens junctions between HSCs and hepatocytes.

DOI： 10.1016/j.ajpath.2020.12.007

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Senescent hepatic stellate cells (senescent HSCs) are found in patients with liver cirrhosis and have been thought to be involved in the development of hepatocellular carcinoma (HCC) in mice via the senescence-associated secretory proteins. However, in humans, which secretory proteins are involved and what regulate their expression remain unclear. In the current study, we characterized senescence-associated β-galactosidase-positive senescent human HSCs (hHSCs) induced by repetitive passaging. They exhibited enhanced expression of 14 genes for secretory protein and persistent phosphorylation of ERK1/2 protein but not JNK or p38 MAPK proteins. Enhanced nuclear ERK1/2 phosphorylation was observed in senescent hHSCs. Treatment of the senescent hHSCs with ERK1/2 inhibitor, SCH772984, significantly decreased the levels of angiopoietin like 4 (ANGPTL4), C-C motif chemokine ligand 7 (CCL7), Interleukin-8 (IL-8), platelet factor 4 variant 1 (PF4V1), and TNF superfamily member 15 (TNFSF15) mRNA levels in a dose-dependent manner. The enhanced phosphorylation of ERK1/2 and expression of ANGPTL4, IL-8 and PF4V1 genes were observed in both of senescent human dermal fibroblasts and X-ray-induced senescent hHSCs. However, transient ERK1/2 activation induced by epidermal growth factor could not mimic the gene profile of the senescent hHSCs. These results revealed involvement of ERK1/2 signaling in the regulation of senescence-associated secretory factors, suggesting that simultaneous induction of ANGPTL4, IL-8, and PF4V1 genes is a marker of hHSC senescence. This study will contribute to understanding roles of senescent hHSCs in liver diseases.

DOI： 10.1007/s11010-018-3466-x

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s11010-018-3466-x

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.14814/phy2.13556

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.14814/phy2.13556

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s13075-017-1349-2

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Leucine-rich alpha 2 glycoprotein (LRG) has been identified as a serum protein elevated in patients with active rheumatoid arthritis (RA). Although the function of LRG is ill-defined, LRG binds with transforming growth factor (TGF)-β and enhances Smad2 phosphorylation. Considering that the imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg) plays important roles in the pathogenesis of RA, LRG may affect arthritic pathology by enhancing the TGF-β-Smad2 pathway that is pivotal for both Treg and Th17 differentiation. The purpose of this study was to explore the contribution of LRG to the pathogenesis of arthritis, with a focus on the role of LRG in T cell differentiation. METHODS: The differentiation of CD4 T cells and the development of collagen-induced arthritis (CIA) were examined in wild-type mice and LRG knockout (KO) mice. To examine the influence of LRG on T cell differentiation, naïve CD4 T cells were isolated from LRG KO mice and cultured under Treg- or Th17-polarization condition in the absence or presence of recombinant LRG. RESULTS: In the CIA model, LRG deficiency led to ameliorated arthritis and reduced Th17 differentiation with no influence on Treg differentiation. By addition of recombinant LRG, the expression of IL-6 receptor (IL-6R) was enhanced through TGF-β-Smad2 signaling. In LRG KO mice, the IL-6R expression and IL-6-STAT3 signaling was attenuated in naïve CD4 T cells, compared to wild-type mice. CONCLUSIONS: Our findings suggest that LRG upregulates IL-6R expression in naïve CD4 T cells by the enhancement of TGF-β-smad2 pathway and promote Th17 differentiation and arthritis development.

DOI： 10.1186/s13075-017-1349-2

PubMed

Publishing type：Research paper (scientific journal)  

Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy.

DOI： 10.1177/1534735415610427

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1177/1534735415610427

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1089/jmf.2014.3380

PubMed

Publishing type：Research paper (scientific journal)  

Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic steatohepatitis, ultimately leading to cirrhosis and liver cancer. It is important to prevent this progression during the initial stages of hepatic fatty degeneration. Maltitol is a polyol produced by the hydrogenation of maltose. We investigated the efficacy of maltitol for treating hepatic fatty degeneration in C57BL/6 male mice using a high-fat diet model. Intake of 5.0% maltitol for 8 weeks significantly suppressed weight gain, hepatic fatty degeneration, hyperglycemia, and hypercholesterolemia. With maltitol intake, sterol regulatory element-binding protein 1c (SREBP1c) mRNA expression was significantly decreased, and farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR), and hydroxymethylglutaryl-Co reductase expressions were significantly higher in the liver. The increase in SREBP1c and suppression of FXR and PPAR expressions are correlated with NAFLD. Our results suggest that maltitol may prevent steatosis of NAFLD with a high-fat diet.

DOI： 10.1089/jmf.2014.3380

Publishing type：Research paper (scientific journal)  

DOI： 10.3109/13685538.2015.1017809

PubMed

Publishing type：Research paper (scientific journal)  

Androgen deprivation therapy (ADT) for the treatment of prostate cancer (PCa) causes an increase in total body fat, leading to a net gain in body weight. Moreover, the use of the luteinizing hormone-releasing hormone agonists in ADT causes a decrease in serum androgen levels, leading to the development of metabolic syndrome (MetS). Androgen blockade significantly increases plasma adiponectin levels, which has some efficacy against MetS, whereas ADT increases fasting plasma insulin and decreases insulin sensitivity, suggesting that there are other mechanisms involved in the onset of MetS besides adiponectin activation. We investigated the effects of ADT on serum aP2 and adiponectin in PCa patients. Six months post-ADT, serum aP2 and adiponectin levels were significantly increased, although there were no changes in patient body weight and no correlation between the changes in serum aP2 and total adiponectin levels. The serum adiponectin and aP2 levels have independent implications in ADT for PCa; therefore, their combined measurement will clarify the impact on the development of obesity-related diseases during ADT. Contrary to adiponectin, high serum aP2 levels were correlated with the late development of MetS. Further studies are needed to investigate the future occurrence of metabolic diseases post-ADT.

DOI： 10.3109/13685538.2015.1017809

Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpgi.00294.2014

PubMed

Publishing type：Research paper (scientific journal)  

Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-alpha, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-beta was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-alpha, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-alpha, IL-1 beta, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.

DOI： 10.1152/ajpgi.00294.2014

Publishing type：Research paper (scientific journal)  

Chemotherapy improves the outcome of cancer treatment, but patients are sometimes forced to discontinue chemotherapy or drop out of a clinical trial due to adverse effects, such as gastrointestinal disturbances and suppression of bone marrow function. The objective of this study was to evaluate the safety and effectiveness of a mushroom product, active hexose correlated compound (AHCC), on chemotherapy-induced adverse effects and quality of life (QOL) in patients with cancer. Twenty-four patients with cancer received their first cycle of chemotherapy without AHCC and then received their second cycle with AHCC. During chemotherapy, we weekly evaluated adverse effects and QOL via a blood test, EORTC QLQ-C30 questionnaire, and DNA levels of herpes virus type 6 (HHV-6) in saliva. The DNA levels of HHV-6 were significantly increased after chemotherapy. Interestingly, administration of AHCC significantly decreased the levels of HHV-6 in saliva during chemotherapy and improved not only QOL scores in the EORTC QLQ-C30 questionnaire but also hematotoxicity and hepatotoxicity. These findings suggest that salivary HHV-6 levels may be a good biomarker of QOL in patients during chemotherapy, and that AHCC may have a beneficial effect on chemotherapy-associated adverse effects and QOL in patients with cancer undergoing chemotherapy. © 2014 Taylor and Francis Group, LLC.

DOI： 10.1080/01635581.2014.884232

PubMed

Publishing type：Research paper (scientific journal)  

DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

Publishing type：Research paper (scientific journal)  

DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

DSS誘導腸炎モデルマウスを用いてシソエキスの有効性を検討した。炎症惹起後にシソエキスを内服させることによって体重の回復が早くなり、腸管におけるTNF-αやIL-17AなどのmRNA発現が有意に抑制されていた。また、炎症を起こした粘膜固有層の抑制性T細胞がシソエキスによって増加していた。シソエキスの代表的な成分であるルテオリン、アピゲニン、ロスマリン酸を用いて単核球からのサイトカイン分泌を調べたところルテオリンには強い炎症性サイトカイン産生抑制効果が確認され、アピゲニンやロスマリン酸にはIL-10産生促進効果があることがわかった。(著者抄録)

Publishing type：Research paper (scientific journal)  

DOI： 10.1080/01635581.2014.884232

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ajpath.2013.08.012

PubMed

Publishing type：Research paper (scientific journal)  

IL-10-deficient mice spontaneously develop intestinal inflammation, which has many similarities to Crohn's disease. Several reports suggest that epithelial cell death may increase the severity of colitis
however, decisive evidence is lacking. In the present report, we addressed whether and how epithelial cell death plays a role in the development of chronic colitis. We first examined the morphological characteristics of intestines of IL-10-deficient mice and found two forms of epithelial cell death (typical apoptosis and necrosis-like cell death) in colitis. To elucidate the pathological roles of epithelial cell death, we crossbred IL-10-deficient knockout mice with Bcl-2 transgenic mice, in which the anti-apoptosis protein Bcl-2 was overexpressed in intestinal epithelial cells, but not in immune cells. Epithelial cell-specific Bcl-2 protected IL-10 deficiency-induced colitis and markedly reduced their symptoms. Interestingly, morphological analysis revealed that Bcl-2 suppressed apoptosis and necrosis-like cell death, and better maintained mucosal barrier in IL-10-deficient mice. From the immunological aspect, Bcl-2 did not alter the activation of T-helper cell 1 but inhibited the growth of T-helper cell 17, suggesting that mucosal integrity may control the immune responses. These results provide genetic evidence demonstrating that epithelial cell death is crucial for the development of chronic colitis. © 2013 American Society for Investigative Pathology.

DOI： 10.1016/j.ajpath.2013.08.012

PubMed

Publishing type：Research paper (scientific journal)  

【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

Publishing type：Research paper (scientific journal)  

【背景】災害の負傷者、遺族らにおいて、一般保険医療では治療困難な後遺障害に対し、補完代替医療(CAM)に救いを求めることも少なくない。しかしその安全性、効果に対してのエビデンスは乏しい。【方法】この臨床試験は大阪大学医学部附属病院にて災害後遺障害者に対して施行した。そのうちJR福知山線脱線事故の被害者、遺族ら9人に対して解析を行った。一般保険医療が新たに必要な者、もしくは一般保険医療を受診も治療途中で、状態が落ち着いていない者を除外した。主要評価項目は介入完遂率とした。副次評価項目は抑うつ症状、PTSD様症状、介入の満足度、身体的、精神的苦痛などとした。鍼とアロマトリートメントを被検者に選んでもらい(両方も可)、週1回8週間にわたる介入が行われた。【結果】9例全てが鍼とアロマトリートメント両方を選び、完遂した。重篤な有害事象を認めなかった。介入直後は、身体的、精神的苦痛の有意な改善を認めた。介入を通じては、身体的、精神的苦痛の有意な改善は認めなかった。介入を通して、抑うつ尺度の有意な改善を認めた。(著者抄録)

Publishing type：Research paper (scientific journal)  

【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

Publishing type：Research paper (scientific journal)  

【背景】肥満は過栄養を介し、多くの癌の発症におけるリスクファクターと考えられている。そこで、生活習慣との関連が示唆される癌患者を対象に、医師、管理栄養士、臨床心理士、鍼灸師、アロマセラピストがチームとなり、統合的な介入を行い、BMI(Body Mass Index)の適正化と血中アディポネクチン濃度の改善を目的として、QOLの改善と合併症の軽減を目指す臨床試験を開始した。【方法】毎月1回介入を実施し、期間は1年とした。心理評価の実施や認知行動療法を取り入れた生活指導、鍼治療とアロマセラピーを含む森林療法を実施した。【結果】1年後のBMI・血中のアディポネクチン濃度は有意に改善した。森林療法の実施前後に測定したPOMS(Profile Mood States)においても有意な改善がみられた。【結語】生活習慣病型癌患者に対し、生活指導に加え、鍼灸治療やアロマセラピー、森林療法などの補完代替医療を集学的に実施する統合的なライフスタイルの介入は有用であると考えられた。(著者抄録)

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.parint.2009.07.001

PubMed

Publishing type：Research paper (scientific journal)  

The 28S rDNA from nine species of the genus Syphacia collected in Japan was sequenced, and the phylogenetic relationship was inferred from multiple sequence alignment of 28S FDNA by the MAFFT program. Phylogenetic tree indicates that S. petrusewiczi, which was the only species belonging to the subgenus Seuratoxyuris, has diverged earlier than other rodent pinworms examined and was distantly separated from the others genetically. It was revealed that S. agraria and S. vandenbrueli, whose subgeneric status has not been specified, belonged to the subgenus Syphacia together with other 6 species. Syphacia motana from Clethrionomys, Eothenomys and Microtus was very closely related to S. obvelata from Mus, and that S. frederici from Apodemus and S. vandenbrueli from Micromys were comparatively closely related to the former two species. The phylogenetic relationship among the three species of Syphacia found in Japanese Apodemus was inconsistent with the biogeography of host rodents. The co-evolutionary relationship between pinworm species and their host rodents may not be so strict and host switching has probably occurred frequently during the Course of evolution. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.parint.2009.07.001

Publishing type：Research paper (scientific journal)  

PubMed

Publishing type：Research paper (scientific journal)  

Species of the genus Syphacia are considered to have generally co-evolved with their rodent hosts. This study detennined partial sequences of the CO1 gene from several species in the genus Syphacia and discuss the relationships between pinworms and their hosts. Syphacia montana, which parasitizes Microtinae, was closely related to S. frederici and S. obvelata, which parasitize Murinae. Although both S. obvelata and S. ohtaorum parasitize rodents in the genus Mus, these two species were not found to be closely related to each other. Syphacia frederici, S. emileromani and S. agraria are all pinworms of the Apodemus species, but genetic affiliation between these three species was not indicated. These facts suggest that the co-evolutionary relationship between species of the genus Svphacia and their host rodents may not so strict and host switching has probably occurred during the course of evolution.

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

肝星細胞は肝小葉内で唯一ディッセ腔に存在する間葉系細胞であり、spineと呼ばれる突起を肝細胞へと伸ばし接着結合を形成している。しかしながら各種肝病態下でのサイトカインやケモカインなどの外因性刺激によって肝星細胞は活性化し、筋線維芽細胞へと形質転換することで間質細胞としての機能亢進を引き起こす。活性化肝星細胞は、肝細胞との接着を消失させた後、炎症部位に遊走、増殖し、線維化をもたらすと考えられる。細胞接着結合は単なる接着装置としての機能だけでなく、細胞内シグナル伝達を介して増殖や分化などを制御している。今回我々は肝星細胞における肝細胞との接着結合が肝星細胞の活性化抑制に寄与しており、この接着結合の消失が肝星細胞活性化の新規initiation factorであることを明らかにしたので報告する。(著者抄録)

J-GLOBAL

J-GLOBAL

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

CiNii Article

チアゾリジン誘導体は、ペルオキシソーム増殖因子活性化受容体γ(PPARγ)のリガンドでインスリン抵抗性改善作用を有し、糖尿病患者の血糖コントロールに寄与している。また、他にも心血管イベントに対するベネフィットも報告されている。一方、大規模疫学調査により膀胱がんの発生リスクを上昇させるという報告もある。膀胱がんの発症には人種差、性差が認められるため、日本人を対象とした疫学研究が必要である。しかし、疫学研究の限界も踏まえ、臨床現場においてはリスク-ベネフィットを考慮した処方が必要である。(著者抄録)

J-GLOBAL

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