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      • Germinal center‐specific protein human germinal center associated lymphoma directly interacts with both myosin and actin and increases the binding of myosin to actin

        Lu, Xiaoqing,Kazmierczak, Katarzyna,Jiang, Xiaoyu,Jones, Michelle,Watt, James,Helfman, David M.,Moore, Jeffrey R.,Szczesna‐,Cordary, Danuta,Lossos, Izidore S. Blackwell Publishing Ltd 2011 The FEBS journal Vol.278 No.11

        <P>Human germinal center associated lymphoma (HGAL) is a germinal center‐specific gene whose expression correlates with a favorable prognosis in patients with diffuse large B‐cell and classic Hodgkin lymphomas. HGAL is involved in negative regulation of lymphocyte motility. The movement of lymphocytes is directly driven by actin polymerization and actin–myosin interactions. We demonstrate that HGAL interacts directly and independently with both actin and myosin and delineate the HGAL and myosin domains responsible for the interaction. Furthermore, we show that HGAL increases the binding of myosin to F‐actin and inhibits the ability of myosin to translocate actin by reducing the maximal velocity of myosin head/actin movement. No effects of HGAL on actomyosin ATPase activity and the rate of actin polymerization from G‐actin to F‐actin were observed. These findings reveal a new mechanism underlying the inhibitory effects of germinal center‐specific HGAL protein on lymphocyte and lymphoma cell motility.</P>

      • SCISCIESCOPUS

        HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway

        Jiang, Xiaoyu,Lu, Xiaoqing,McNamara, George,Liu, Xiaofei,Cubedo, Elena,Sarosiek, Kristopher A.,,nchez-Garcí,a, Isidro,Helfman, David M.,Lossos, Izidore S. American Society of Hematology 2010 Blood Vol.116 No.24

        <B>Abstract</B><P>HGAL is a germinal center (GC)-specific gene that negatively regulates lymphocyte motility and whose expression predicts improved survival of patients with diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). We demonstrate that HGAL serves as a regulator of the RhoA signaling pathway. HGAL enhances activation of RhoA and its down-stream effectors by a novel mechanism - direct binding to the catalytic DH-domain of the RhoA-specific guanine nucleotide exchange factors (RhoGEFs) PDZ-RhoGEF and LARG that stimulate the GDP-GTP exchange rate of RhoA. We delineate the structural domain of HGAL that mediates its interaction with the PDZ-RhoGEF protein. These observations reveal a novel molecular mechanism underlying the inhibitory effects of GC-specific HGAL protein on the motility of GC-derived lymphoma cells. This mechanism may underlie the limited dissemination and better outcome of patients with HGAL-expressing DLBCL and cHL.</P>

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        Fenugreek Bread: A Treatment for Diabetes Mellitus

        Jack N. Losso,Darryl L. Holliday,John W. Finley,Roy J. Martin,Jennifer C. Rood,Ying Yu,Frank L. Greenway 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5

        Use of fenugreek, a food with demonstrated efficacy in lowering blood sugar, is limited by its bitter taste and strong flavor. A bread incorporating fenugreek using a proprietary process was tested for its taste acceptability and its effect on carbohydrate metabolism. We developed a fenugreek bread formula that was produced in a commercial bakery by incorporating fenugreek flour into a standard wheat bread formula. Whole wheat bread was prepared by the same formula in the same bakery using wheat flour. Eight diet-controlled diabetic subjects were served two slices (56g) and 5% fenugreek. Blood glucose and insulin were tested periodically over a 4-hour period after consumption. The tests were run on two occasions 1 week apart, once with the fenugreek bread and once with regular bread. The study was double-blind, and the order was randomized and balanced. Fenugreek and whole wheat bread samples were evaluated for sensory attributes and nutrient composition. There was no statistically significant difference in proximate composition, color, firmness, texture, and flavor intensity between the fenugreek and wheat bread (P>.05). The area under the curve for glucose and insulin was lower in the fenugreek condition, but only reached significance with insulin (P<.05). The fenugreek-containing bread was indistinguishable from the whole wheat bread control. Normally, fenugreek flour impacts bread quality negatively. The bread maintained fenugreek's functional property of reducing insulin resistance. Acceptable baked products can be prepared with added fenugreek, which will reduce insulin resistance and treat type 2 diabetes.

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        Sodium Propionate or Sodium Butyrate Promotes Fatty Acid Oxidation in HepG2 Cells Under Oxidative Stress

        Kristina J. Cook,Ann Coulter,Michael Keenan,Frank Greenway,Jack N. Losso 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.1

        The beneficial effects of sodium butyrate (NaB) and sodium propionate (NaP) on fatty acid oxidation (FAO) genes and production of proinflammatory cytokines related to nonalcoholic fatty liver disease (NAFLD) were evaluated using HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or lipopolysaccharides (LPSs) as a model. The results showed that NaP or NaB was able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1α), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce greater effects by increasing CPT1α, PPARα, and UCP2 mRNA expression in LPS-treated HepG2 cells and by increasing CPT1α and ATGL mRNA expression in palmitate-/oleate-treated HepG2 cells. Only NaP treatment significantly increased FGF21 mRNA expression in palmitate-/oleate-treated HepG2 cells. The enzyme-linked immunosorbent assay results revealed that only pretreatment with LPSs and not palmitate/oleate significantly increased tumor necrosis factor alpha (TNF-α) expression in HepG2 cells. NaP alone or in combination with NaB significantly decreased TNF-α expression in LPS-induced HepG2 cells. The expression of interleukin-8 in both models showed no significant differences in all treatments. NaP and NaB show potential for in vivo studies on NAFLD.

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