Effect of sorbitol on dough rheology and quality of sugar replaced cookies

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Mohammad Ali Shariati

2018-02-01

Full Text Available A high amount of sugar is used in bakery products, which may cause diabetes, high blood glucose levels and obesity. Due to these reasons, sugar is being replaced with substitutes. There is different carbohydrate-based sugar substitutes (polyols that can efficiently replace sugar. Among polyols, sorbitol is an efficient replacer that can mimic sugar with minimal effects on cookie quality. Effects of different sorbitol levels (0 to 12.5% were seen on the dough rheology. Mixographic studies showed that peak height and mixing time reduced with the addition of sorbitol. Farinographic studies showed that water absorption and the mixing tolerance index of dough reduced with the supplementation of sorbitol, whereas dough development time, arrival time, dough stability time and softening of dough increased. Extensographic studies revealed that sorbitol substitution produced hard, cohesive, adhesive and elastic dough. Sugar in cookies formulations was reduced from 100 to 50% by replacing with sorbitol 0 to 50%. Physical analysis of sorbitol containing cookies showed that the diameter and spread factor of cookies decreased with higher levels of sorbitol, whereas thickness, color, hardness and water activity of cookies increased. The calorific value of cookies decreased with the increasing levels of sorbitol. At upto 20% replacement of sugar, other parameters of cookies were not affected. Sensory evaluation of the cookies showed that hedonic points for sensory evaluation parameters reduced with the increasing levels of sorbitol, T2 (20% replacement showed maximum overall acceptability. Normal 0 false false false EN-GB X-NONE AR-SA

Influence of time orientation on food choice: Case study with cookie labels.

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Tórtora, Giuliana; Ares, Gastón

2018-04-01

Time orientation can influence health-related behaviors, including food consumption. The aim of the present work was to study the influence of time orientation on food choice, using cookie labels as case study. A choice-conjoint task was designed using labels differing in type of cookie (chocolate chips vs. granola), front-of-pack nutrition information (nutritional warnings vs. Facts Up Front system) and nutritional claim (no claim vs. "0% cholesterol. 0% trans fat"). An online study was conducted, in which 155 participants evaluated 8 pairs of cookie labels and selected the one they would buy if they were in the supermarket. Then, they were asked to complete a consideration of future consequences scale (CFC) adapted to eating habits, as well as a questionnaire about socio-demographic characteristics. Time orientation influenced participants' choices of cookies labels; particularly the importance attached to type of cookie. Participants with greater consideration of future consequences preferred the granola cookies, associated with health, while those who prioritized immediate consequences preferred chocolate chip cookies. In addition, nutritional warnings discouraged choice regardless of participants' time orientation. Results from the present work provide additional evidence of the influence of time preferences on food choices and suggest that strategies to stimulate and generate a more future-oriented perspective on eating habits could contribute to more healthful food choices. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Whole Multigrain Blends Addition on Quality Characteristics of Cookies

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Adriana Păucean

2015-11-01

Full Text Available Whole grain cereal products are important components of the daily diet worldwide. A high consumption of these products is associated with a decreased risk of diabetes, myocardial infarctions, and certain cancers. This study aimed to asses the effect of the whole multigrain flour (wheat, rye, barley and oats incorporation at different levels (8%, 10% on the quality characteristics of cookies. Moisture, ash, fat, protein, reducing carbohydrates, alkalinity, water absorption and impregnation index of blends and cookies were determined. The sensory profile was obtained by a 9 points hedonic test. Incorporation of multigrain flour in cookies could be a powerful tool to obtain food with enhanced nutritional characteristics.Whole grain cereal products are important components of the daily diet worldwide. A high consumption of these products is associated with a decreased risk of diabetes, myocardial infarctions, and certain cancers. This study aimed to asses the effect of the whole multigrain flour (wheat, rye, barley and oats incorporation at different levels (8%, 10% on the quality characteristics of cookies. Moisture, ash, fat, protein, reducing carbohydrates, alkalinity, water absorption and impregnation index of blends and cookies were determined. The sensory profile was obtained by a 9 points hedonic test. Incorporation of multigrain flour in cookies could be a powerful tool to obtain food with enhanced nutritional characteristics.

Effect of co-milled wheat, green gram and barley on the rheological and quality characteristics of cookies.

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Tulse, Siddharth B; V, Reshma; Rajiv, Jyotsna; Sakhare, Suresh D

2015-10-01

Studies were carried out on the co-milling of wheat (W), green gram (GG) and barley (BR) grains using a roller milling system. The co-milled straight run flours obtained by varying proportions of wheat, barley and green gram WGGBR-1 (90:5:5), WGGBR-2 (80:10:10) and WGGBR-3 (70:15:15) were used in the cookie baking experiments. As the amount of GG and BR increased in blend, water absorption increased (56.5-58.4%) and dough stability and extensibility values decreased (104-92 mm). Hardness of cookie doughs and spread ratio (7.70-6.00) of cookies decreased and breaking strength values increased from 2900 to 3700 g in cookies made using co-milled blends WGGBR-1, WGGBR-2 and WGGBR-3. The highest breaking strength value (3700 g), large islands, gummy mouth feel and lowest overall quality score of 51.5 were recorded for cookies made with blend WGGBR-3 indicating that the cookies had unacceptable hard texture. The optimum blend for cookies was WGGBR-2 (80:10:10) and the cookies possessed slightly small islands, crisp, light texture and a pleasant taste. These cookies had 12.30 and 8.00% protein and dietary fibre as against the control cookie values of 8 and 4%, respectively. The in vitro protein digestibility of the control cookies was 61% and it was 51% for cookies made with WGGBR-2 blend. © The Author(s) 2014.

Optimization of a Functional Cookie Formulation by Using Response Surface Methodology

International Nuclear Information System (INIS)

Lee, L.Y.; Tan, K.S.; Liew, S.L.

2011-01-01

A functional cookie formulation containing oligo fructose, dietary fibre and lower calorie, fat and sugar contents than conventional cookies was optimized using Response Surface Methodology (RSM). Instant N-Oil II was used as a fat replacer, while Raftilose P95 was used as a sugar substitute with the addition of fructose to enhance sweetness. Selection of the optimal formulation was based on caloric content. An optimized formulation, V1, was obtained from the model Y = 4927.70 - 152.34X 1 - 155.42X 3 + 104.20X 3 2 + 151.71X 3 3 - 95.08X 3 4 , where Instant N-Oil II replaced 30 % of butter and 24.4 %, w/w (30.5 g) fructose replaced 40.0 %, w/w (50.0 g) sucrose. Two additional optimized formulations, S1 and S2, were proposed which contained the same ingredients as V1, but both contained 19.0 %, w/w (23.8 g) Raftilose P95. Also, S2 had a higher fat replacement level (42 %). A reference cookie prepared from a conventional recipe received significantly higher scores (P < 0.05) than the functional cookies V1, S1 and S2 in the sensory evaluation. However, when health benefits of the functional cookies were explained to the panel after the sensory evaluation had concluded, majority of the panelists stated that they would prefer S1, had they known of its health benefits. S1 contained 19.04 % fat, 8.62 % fructose and 0.74 % sucrose, namely, significantly lower fat and sucrose levels and higher fructose content than the conventional cookie. (author)

Effects of incorporation of whey protein concentrate on physicochemical, texture, and microbial evaluation of developed cookies

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Safa Hamid Wani

2015-12-01

Full Text Available Whey Protein concentrate (WPC was incorporated into cookies at different levels (0, 2, 4, and 6%. Cookies were analyzed for physicochemical, color, textural, microbial, and sensory attributes. Physicochemical analysis revealed that 6% WPC supplemented cookies shows maximum protein content (13.22%, moisture content (11.33%, fat content (23.08%, and ash content (2.02% as compared to control. However, control sample shows significantly different (p ≤ 0.05 value for crude fiber and carbohydrate content. Maximum thickness (9.63 mm, diameter (44.06 mm, and weight (9.10 g were found for control and these decreased significantly (p ≤ 0.05 with increase in WPC supplementation level in cookies. Cookie supplemented with 4% WPC showed maximum overall acceptability (4.76. Texture analysis revealed that 6% WPC supplemented cookie shows maximum cutting force (55.3 N. Lightness (L* value of cookies decreased from 67.32 to 57.94. Where as a* and b* value increased from 0.37 to 3.57 and 25.35 to 27.54, respectively. The total plate count of cookie samples was under acceptable limits.

Incorporation of buriti endocarp flour in gluten-free whole cookies as potential source of dietary fiber.

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Becker, Fernanda Salamoni; Damiani, Clarissa; de Melo, Adriane Alexandre Machado; Borges, Paulo Rogério Siriano; Boas, Eduardo Valério de Barros Vilas

2014-12-01

Cookies were prepared by replacing a mixture of brown rice flour (70%) and corn starch (30%) (BRFCS) by buriti endocarp flour (BEF) (0, 5, 10, 15 or 20%). BEF figured as a potential source of dietary fiber (70.53 g 100 g(-1)), especially of insoluble fiber (67.50 g 100 g(-1)), and gluten-free whole cookies showed increased dietary fiber content by adding 5, 10, 15 and 20% BEF (8.58 to 20.02 g 100 g(-1)) when compared to control cookie (6.91 g 100 g(-1)). The addition of BEF affected diameter, spread ratio, color and texture of cookies. All cookies added with BEF were darker, harder and presented smaller diameter and smaller spread ratio than the control cookie. These difference increased proportionally to level of substitution of BRFSC by BEF. Gluten-free whole cookies with up to 15% BEF were well accepted by consumers. Therefore, the use of BEF in cookies may increase the availability of functional ingredients source of dietary fiber for celiac consumers, add economic value to buriti processing by-products and decrease environmental impacts due to the high amounts of waste generated by buriti processing industries.

Influence of cookies composition on temperature profiles and qualitative parameters during baking

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Ž. Kožul

2014-01-01

Full Text Available During baking of bakery products temperature of baking, temperature profiles, moisture content, volume and colour changes are strongly coupled. The objective of this paper was to study the influence of the cookies composition on temperature profiles and quality parameters (width and thickness, colour formation and textural properties: hardness, fracturability and work of breaking force during baking process. Composition of cookies differs due to flour type and initial moisture content. Cookies were baked at 205 °C and temperature was measured in the centre of samples which were 7 mm thick with a 60 mm diameter. The results of temperature profiles of the cookies during baking have shown the same trend for all of the 18 samples. Samples with the higher initial water content have lower values of total colour difference and also significantly affect textural properties.

Investigation of variations in the acrylamide and N(ε) -(carboxymethyl) lysine contents in cookies during baking.

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Cheng, Lu; Jin, Cheng; Zhang, Ying

2014-05-01

Baking processing is indispensable to determine special sensory prosperities of cookies and induces the formation of some beneficial components such as antioxidants. However, the formation of some Maillard reaction-derived chemical hazards, such as acrylamide (AA) and N(ε) -(carboxymethyl) lysine (CML) in cookies is also a significant consequence of baking processing from a food safety standpoint. This study investigated the effects of baking conditions on the formation of AA and CML, as well as the antioxidant activity (AOA) of cookies. Cookies were baked at various baking temperatures (155 to 230 °C) and times (1.5 to 31 min). AA and CML contents were determined by ultra-performance liquid chromatography-tandem mass spectrometry, respectively. The highest level of AA was obtained in the cookies baked at 155 °C/21 min and 205 °C/11 min (328.93 ± 3.10 μg/kg and 329.29 ± 5.29 μg/kg), while the highest level of CML was obtained in the cookies baked at 230 °C/1.5 min (118.05 ± 0.21 mg/kg). AA was prone to form at relatively low temperature range (155 to 205 °C), however, CML at relatively high temperature range (205 to 230 °C). The CML content was much higher than the AA content in the same set of cookies, by about 2 to 3 orders of magnitude. The AOA of cookies increased at more severe baking conditions. According to the AA and CML content, AOA and sensory properties of cookies, the temperature-time regime of 180 °C/16 min might be a compromised selection. However, only optimizing the baking condition was not enough for manufacture of high-quality cookies. Cookies, a kind of widely consumed bakery products in the world, contain some potentially harmful compounds, like acrylamide (AA) and N(ε) -(carboxymethyl) lysine (CML). AA in cookies has led to public health concern and several research efforts. But CML, another Maillard reaction-derived chemical hazard, has been neglected so far, even though its content is much higher than that of AA in cookies. The

Micro-Sugar-Snap and -Wire-Cut Cookie Baking with Trans- and Zero-Trans-Fat Shortenings

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The effect of trans- and zero-trans-fat shortenings on cookie-baking performance was evaluated, using the two AACC micro-cookie-baking methods. Regardless of fat type, sugar-snap cookies made with a given flour were larger in diameter, smaller in height, and greater in weight loss during baking tha...

Flour sodium dodecyl sulfate (SDS)-extractable protein level as a cookie flour quality indicator.

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Pareyt, Bram; Bruneel, Charlotte; Brijs, Kristof; Goesaert, Hans; Delcour, Jan A

2010-01-13

Flour characteristics of laboratory-milled flour fractions of two wheat cultivars were related to their cookie-baking performance. Cultivar (cv.) Albatros wheat milling yielded fractions with lower damaged starch (DS) and arabinoxylan levels and higher sodium dodecyl sulfate-extractable protein (SDSEP) levels than did cv. Meunier wheat milling. During baking, cv. Albatros flour doughs spread faster and set later than their cv. Meunier counterparts and, hence, resulted in larger cookie diameters. DS levels negatively affected spread rate during both cv. Albatros (R2=0.68) and cv. Meunier (R2=0.51) cookie baking. SDSEP levels also influenced cookie quality. The use of flour heat-treated to reduce its SDSEP levels to different degrees led to reduction of the set time (R2=0.90). It was deduced that larger gluten polymer sizes limit dough spread time during baking and that, apart from DS level, the SDSEP level is an indicator for cookie flour quality.

The influence of baking time and temperature on characteristics of gluten free cookies enriched with blueberry pomace

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Šarić Bojana M.

2014-01-01

Full Text Available Blueberry pomace, by-product of juice production, was processed into a new food ingredient by drying and grinding and used for a new gluten-free cookies' formulation, with the aim of improving nutritional profile and antioxidant capacity. Since duration and temperature at which dough is thermally treated during baking highly influence the quality of a baked product, the objective of this work was to optimise the baking conditions in order to obtain the best technological quality of the cookies. Referring to the results obtained at 160 and 170 °C and different baking times, the following was found: the difference in baking conditions caused variation between cookies' diameters of less than 1%, more regular shape of the cookies was obtained when baking time was shorter, hardness of cookies is highly correlated with moisture content, water activity, baking loss and short/long diameter ratio values. The colour characteristics (L*, a* and b* of cookies' top and bottom surfaces indicated that the cookies were not overbaked under the chosen baking conditions. Baking time of 14 min at 170°C was found to be the optimal baking conditions for the blueberry pomace enriched gluten-free cookies.

Functional and sensory properties of cookies prepared from wheat flour supplemented with cassava and water chestnut flours

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Anu Bala

2015-12-01

Full Text Available Functional and sensory properties of cookies prepared by supplementing different proportions of cassava flour (CF and water chestnut flour (WCF blends (0–100% to wheat flour (WF were studied. Seven formulations of cookies were prepared from (a Control (100% WF, (b 30% WF, 35% WCF and 35% CF, (c 27% WF, 37.5% WCF and 37.5% CF, (d 20% WF, 40% WCF and 40% CF, (e 15% WF, 42.5% WCF and 42.5% CF, (f 10% WF, 45% WCF and 45% CF, and (g 0% WF, 50% WCF and 50% CF. Cookies were subjected to physical analysis (cookie diameter, cookie thickness, spread ratio, bulk volume, bulk density, breaking strength, and color analysis and evaluated for consumer acceptance by descriptive sensory analysis. Cookies prepared from water chestnut and cassava flour had low moisture content (5.63%, low fat (24.87%, higher spread ratio (8.148, decreased L, a and b values (dark color, and low breaking strength than control ones. Sensory evaluation established that cookies prepared from 50% WCF and 50% CF were more acceptable than cookies prepared from other formulations.

The suitability of teff flour in bread, layer cakes, cookies and biscuits.

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Coleman, Jennifer; Abaye, A O; Barbeau, William; Thomason, Wade

2013-11-01

A niche market in alternative foods has emerged in response to interest in a health conscientious diet. The purpose of this study was to evaluate the baking characteristics of teff to determine whether teff could produce satisfactory baked products. Cakes, cookies, biscuits and bread were made in triplicate from composites of wheat flour with 0, 10, 20, 30, 40 and 100% teff flour. Objective tests on size, shape, color and texture were used to evaluate the quality of the baked products. Increases in percent teff resulted in decreases in bread and cake volume (p > 0.05). The fracture strength of the cookies were not significantly different (p > 0.05) but spread was significantly greater for cookies made with 40% and 100% teff flour (p ≤ 0.05). There was also significant difference (p ≤ 0.05) in biscuit height and color among teff treatments. Overall, this study showed that teff flour is best suited for use in cookies and biscuits.

Greening in sunflower butter cookies as a function of egg replacers and baking temperature.

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Rogers, Amanda; Hahn, Lan; Pham, Vu; Were, Lilian

2018-04-01

Chlorogenic acid (CGA) binding to proteins in alkaline conditions results in the production of green trihydroxy benzacradine (TBA) derivatives. The formation of TBA derivatives could decrease product quality due to the potential losses in soluble protein and antioxidants and the production of an undesirable green color. To determine how cookie formulation affected the formation of TBA derivatives in sunflower butter cookies, two egg replacers (chia and banana) and two baking temperatures (162.8 and 190.6 °C) were used. Moisture, greening intensity, CGA content and antioxidant capacity were measured. Cookies made with egg and baked at 162.8 °C had the highest moisture, internal greening intensity, and TBA derivative formation, in addition to lower CGA content and antioxidant capacity. Cookies made with banana baked at 190.6 °C produced the opposite outcome with 35, 4, and 23% less internal greening, moisture, and TBA derivatives, respectively, and 90 and 76% higher CGA and antioxidant capacity. Internal greening was positively correlated with moisture and adduct concentration, and negatively correlated with spread factor and CGA content. Moisture had a significant impact on greening, which indicates that baking temperature and cookie dough formulation can be modified to produce a less green cookie with more unreacted antioxidants and protein.

Defatted wheat germ application: Influence on cookies' properties with regard to its particle size and dough moisture content.

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Petrović, Jovana; Rakić, Dušan; Fišteš, Aleksandar; Pajin, Biljana; Lončarević, Ivana; Tomović, Vladimir; Zarić, Danica

2017-10-01

The introduction of agro-food industry by-products rich in bioactive compounds represents major challenge in food industry sector. The influence of wheat germ particle size (Box-Behnken experimental design. The substitution of wheat flour with wheat germ increased the protein, fat, mineral, and fiber content of the cookies. The particle size of wheat germ affected the textural properties of cookies. As the particle size of wheat germ increased, the hardness of cookies decreased. The color of the cookie was most influenced by the interaction of dough moisture content and wheat germ particle size. Wheat germ level up to 15% had no significant effect on the sensory characteristics of cookies. A suitable combination of defatted wheat germ level, its particle size, and dough moisture content can improve the nutritional value of cookies, without causing a negative effect on the cookies' sensory characteristics.

In vitro digestibility of banana starch cookies.

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Bello-Pérez, Luis A; Sáyago-Ayerdi, Sonia G; Méndez-Montealvo, Guadalupe; Tovar, Juscelino

2004-01-01

Banana starch was isolated and used for preparation of two types of cookies. Chemical composition and digestibility tests were carried out on banana starch and the food products, and these results were compared with corn starch. Ash, protein, and fat levels in banana starch were higher than in corn starch. The high ash amount in banana starch could be due to the potassium content present in this fruit. Proximal analysis was similar between products prepared with banana starch and those based on corn starch. The available starch content of the banana starch preparation was 60% (dmb). The cookies had lower available starch than the starches while banana starch had lower susceptibility to the in vitro alpha-amylolysis reaction. Banana starch and its products had higher resistant starch levels than those made with corn starch.

Effect of hydrated apple powder on dough rheology and cookies quality

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Michaela Lauková

2016-10-01

Full Text Available Dietary fiber is a group of food components, which are resistant to human enzymatic digestion. The incorporation of dietary fiber obtained from various sources of fruit and vegetable by-products into the cereal based products such as bread, rolls, cookies, muffins, crackers, cakes and pasta is of growing interest for the food industry. The replacement of wheat flour by dietary fiber from various sources can change physicochemical, textural and organoleptic characteristic of bakery products. Apple pomace is the main by-product produced in the apple fruit processing industry. It is a rich source of carbohydrate, pectin, crude fiber, and minerals. The dietary fiber content in apple pomace ranges between 33 - 35%. The influence of hydrated commercial dietary fiber on wheat dough rheology (5, 10 and 15% flour replacement and physical and sensory properties of cookies was examined. It was found that addition of HAP significantly increased the rheological properties of dough such as water absorption (from 58.0% to 75.3%, dough stability (from 6.7 min to 11.6 min and prolonged dough development time (from 3.5 min to 11.0 min and reduced the mixing tolerance index (from 34.7 BU to 11.9 BU. It was also concluded that hydrated apple powder addition reduced physical properties of cookies such as volume (from 10.4 cm3 to 8.0 cm3, diameter (from 4.7 cm to 4.2 cm, volume index (from 1.35 cm to 1.10 cm and porosity (from 0.32 to 0.24. Sensory properties (taste, odour, stickiness, firmness and density of cookies were also analysed. Cookies with addition of hydrated apple powder had fruity taste and odour and showed high overall acceptance. From this study resulted that hydrated apple powder can be used as potentially source of dietary fiber in cookie formulation. Moreover, addition of apple pomace inhibits the use of any other flavouring ingredients because has a pleasant fruity flavour.

Effect of steam baking on acrylamide formation and browning kinetics of cookies.

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Isleroglu, Hilal; Kemerli, Tansel; Sakin-Yilmazer, Melike; Guven, Gonul; Ozdestan, Ozgul; Uren, Ali; Kaymak-Ertekin, Figen

2012-10-01

Effects of baking method and temperature on surface browning and acrylamide concentration of cookies were investigated. Cookies were baked in natural and forced convection and steam-assisted hybrid ovens at 165, 180, and 195 °C and at different times. For all oven types, the acrlyamide concentration and surface color of cookies increased with increasing baking temperature. Significant correlation was observed between acrylamide formation and browning index, BI, which was calculated from Hunter L, a, and b color values, and it showed that the BI may be considered as a reliable indicator of acrylamide concentration in cookies. Acrylamide formation and browning index in cookies were considered as the first-order reaction kinetics and the reaction rate constants, k, were in the range of 0.023 to 0.077 (min(-1) ) and 0.019 to 0.063 (min(-1) ), respectively. The effect of baking temperature on surface color and acrylamide concentration followed the Arrhenius type of equation, with activation energies for acrylamide concentration as 6.87 to 27.84 kJ/mol; for BI value as 19.54 to 35.36 kJ/mol, for all oven types. Steam-assisted baking resulted in lower acrylamide concentration at 165 °C baking temperature and lower surface color for all temperatures. Steam-assisted baking is recommended as a healthy way of cooking providing the reduction of harmful compounds such as acrylamide for bakery goods, at a minimal level, while keeping the physical quality. The kinetics of acrylamide formation and browning of cookies will possibly allow definition of optimum baking temperatures and times at convectional and steam-assisted baking ovens. The kinetic model can be used by developing baking programs that can automatically control especially a new home-scale steam-assisted hybrid oven producing healthy products, for the use of domestic consumers. © 2012 Institute of Food Technologists®

Rheology, fatty acid profile and storage characteristics of cookies as influenced by flax seed (Linum usitatissimum).

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Rajiv, Jyotsna; Indrani, Dasappa; Prabhasankar, Pichan; Rao, G Venkateswara

2012-10-01

Flaxseed is a versatile functional ingredient owing to its unique nutrient profile. Studies on the effect of substitution of roasted and ground flaxseed (RGF) at 5, 10, 15 and 20% level on the wheat flour dough properties showed that amylograph peak viscosity, farinograph dough stability, extensograph resistance to extension and extensibility values decreased with the increase in the substitution of RGF from 0-20%. The cookie baking test showed a marginal decrease in spread ratio but beyond substitution of 15% RGF the texture and flavour of the cookies was adversely affected. The data on storage characteristics of control and cookies with 15% RGF showed no significant change with respect to acidity of extracted fat and peroxide values due to storage of cookies upto 90 days in metallised polyester pouches at ambient conditions. The gas chromatographic analysis of fatty acid profile indicated that the control cookies contained negligible linolenic acid and the flaxseed cookies contained 4.75 to 5.31% of linolenic acid which showed a marginal decrease over storage. Hence flaxseed could be used as a source of omega-3-fatty acid.

Highly nutritional cookies based on a novel bean-cassava-wheat flour mix formulation

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Diana Carolina Cabal G.

2014-12-01

Full Text Available Nutritional deficiencies are common among children in Colombia, and innovative strategies and supplements are needed in order to effectively address this problem. For example, in Colombia, when measured as ferritin, iron deposits are deficient in 58.2% of children between two and eight years of age. If a formulation is made with highly nutritional ingredients, cookies will have the potential to be used as supplements in children's diets because of their simple manufacturing process, long shelf life, and high acceptability. This study aimed to develop biofortified cookies, based on a bean-cassava-wheat flour mix, for children. The methodology grouped several studies in order to define the best treatment for the production of bean flour and the flour mix to produce cookies, prioritizing the nutritional content and the microbiological and sensorial quality. A production procedure for bean-based flour, suitable for the production of cookies with adequate nutritional, sensorial and microbiological characteristics was obtained. Additionally, the rheological characteristics of the proposed flour mixes permitted other possible uses for the bread-making industry, substituting cereal flours with flours with higher micronutrient contents. However, further studies are needed to determine the nutritional effects of the regular ingestion of biofortified cookies on children.

Effect of flour particle size and damaged starch on the quality of cookies.

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Barak, Sheweta; Mudgil, Deepak; Khatkar, B S

2014-07-01

Two wheat varieties 'C 306' and 'WH 542' were milled to obtain flour fractions of different particle sizes. Various physicochemical parameters such as wet and dry gluten, falling number, solvent retention capacity (SRC), alkaline water retention capacity (AWRC) and damaged starch content of the flour fractions were analyzed. The damaged starch values ranged from 5.14% to 14.79% for different flour fractions and increased significantly with decrease in particle size. AWRC and SRC of the flour fractions also increased with decrease in particle size. AWRC(r = 0.659) showed positive correlation and cookie spread ratio (r = -0.826) was strongly negatively correlated with the damaged starch levels. Hardness of the cookies in term of compression force showed increasing trend as damaged starch of the flour fractions increased. Spread ratio of the cookies ranged from 6.72 to 10.12. Wheat flour of particle size greater than 150 μm produced cookies with best quality.

Develop of a Sweet Cookie with toasted sesame and ground

OpenAIRE

Dr.C. Aldo Hernández-Monzón; Lic. Dialina García-Pedroso; Ing. Jehannara Calle-Domínguez; MSc.Cira Duarte-García

2015-01-01

The sweet cookies nutritionally are rich source of energy and they have great acceptance to world level and the sesame (Sésamum indicum) it is of the family of the oleaginous ones that possesses a high quantity of protein and fat where 80% belongs to the fatty polinsaturadas fundamentally linoleic acid, it has high content of calcium and the presence iron, magnesium and zinc, what makes it a functional food. This work had as objective to develop a sweet cookie with addition of toastedsesame a...

Cookie- versus cracker-baking--what's the difference? Flour functionality requirements explored by SRC and alveography.

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Kweon, Meera; Slade, Louise; Levine, Harry; Gannon, Diane

2014-01-01

The many differences between cookie- and cracker-baking are discussed and described in terms of the functionality, and functional requirements, of the major biscuit ingredients--flour and sugar. Both types of products are similar in their major ingredients, but different in their formulas and processes. One of the most important and consequential differences between traditional cracker and cookie formulas is sugar (i.e., sucrose) concentration: usually lower than 30% in a typical cracker formula and higher than 30% in a typical cookie formula. Gluten development is facilitated in lower-sugar cracker doughs during mixing and sheeting; this is a critical factor linked to baked-cracker quality. Therefore, soft wheat flours with greater gluten quality and strength are typically preferred for cracker production. In contrast, the concentrated aqueous sugar solutions existing in high-sugar cookie doughs generally act as an antiplasticizer, compared with water alone, so gluten development during dough mixing and starch gelatinization/pasting during baking are delayed or prevented in most cookie systems. Traditional cookies and crackers are low-moisture baked goods, which are desirably made from flours with low water absorption [low water-holding capacity (WHC)], and low levels of damaged starch and water-soluble pentosans (i.e., water-accessible arabinoxylans). Rheological (e.g., alveography) and baking tests are often used to evaluate flour quality for baked-goods applications, but the solvent retention capacity (SRC) method (AACC 56-11) is a better diagnostic tool for predicting the functional contribution of each individual flour functional component, as well as the overall functionality of flours for cookie- and/or cracker-baking.

Personality and Social Framing in Privacy Decision-Making: A Study on Cookie Acceptance.

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Coventry, Lynne M; Jeske, Debora; Blythe, John M; Turland, James; Briggs, Pam

2016-01-01

Despite their best intentions, people struggle with the realities of privacy protection and will often sacrifice privacy for convenience in their online activities. Individuals show systematic, personality dependent differences in their privacy decision making, which makes it interesting for those who seek to design 'nudges' designed to manipulate privacy behaviors. We explore such effects in a cookie decision task. Two hundred and ninety participants were given an incidental website review task that masked the true aim of the study. At the task outset, they were asked whether they wanted to accept a cookie in a message that either contained a social framing 'nudge' (they were told that either a majority or a minority of users like themselves had accepted the cookie) or contained no information about social norms (control). At the end of the task, participants were asked to complete a range of personality assessments (impulsivity, risk-taking, willingness to self-disclose and sociability). We found social framing to be an effective behavioral nudge, reducing cookie acceptance in the minority social norm condition. Further, we found personality effects in that those scoring highly on risk-taking and impulsivity were significantly more likely to accept the cookie. Finally, we found that the application of a social nudge could attenuate the personality effects of impulsivity and risk-taking. We explore the implications for those working in the privacy-by-design space.

Effect of baru (Dipteryx alata Vog. addition on the composition and nutritional quality of cookies

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Kelly Aparecida CAETANO

Full Text Available Abstract The use of the defatted baru almond (Dipteryx alata Vog. prevents the production of waste residues after extraction of its oil (partially defatted baru flour, representing a process of interest from an environmental point of view. The aim of this study was to prepare oat cookies with functional properties, replacing 100% soy oil for baru oil and 30% wheat flour for partially defatted baru flour (baru cookie. Baru cookies presented a higher moisture (7.80%, probably due to the high content of dietary fiber (3.78%, resulting in a lower calorie content (457.46 kcal.100 g–1, compared to traditional oat cookies. Changing the formulation resulted in the enrichment of a number of microelements, including phosphorus (~ 197.90 mg.100 g–1 and iron (~ 21.56 mg.100 g–1. Baru oil increased the concentration of unsaturated fatty acids (~ 76.11%, consisting of approximately 50.37% monounsaturated (MUFA, and 25.74% polyunsaturated fatty acids (PUFA. The total phenolic compound content was approximately doubled in the baru cookie. As such, the baru cookie presents an interesting composition from a nutritional point of view, having a high protein and dietary fiber content, in addition to presenting substantial concentrations of iron and oleic acid, and may be used as part of a healthy diet.

Pilot-scale technology development, nutritional and consumer assessment of whole-multigrain cookies as influenced by fructan inclusion.

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Handa, Chanu; Goomer, Sangeeta; Siddhu, Anupa

2011-04-01

The benefits of wholegrain finger millet and sorghum were combined with that of fructan in form of fructoligosaccharide in the pilot-scale production (10 kg) of cookies. Complete nutritional analysis of the cookies was carried out to provide nutritional information to the consumers. Whole-multigrain cookies with fructan can be categorized as "High Fiber" as they suffice 21% daily value (DV) of fiber and a "Good Source" of iron as they suffice 12.8% DV of iron. A total of 300 consumers (M=110 and F=190), aged between 8 and 66 y evaluated cookies. The overall acceptability (OAA) score of 300 consumers was 8.0±0.58 on a 9-point hedonic scale. Females rated cookies significantly (Pconsumers signified ample scope for viability and marketability of cookies at the commercial scale.   Consumers are looking at snack and convenience foods to provide increased fiber in their diet and there is a tremendous interest in low-calorie and low-sugar foods. The demand of whole and multigrain products is also on the rise because of the Government's emphasis. The present study would assist in assessing feasibility of commercial production of such novel health foods. Together with this, it will ascertain the marketability and commercial viability of the product by means of the consumer preference trials. Availability of such cookies in the market would offer consumers "health" with "convenience" and "taste."

Personality and Social Framing in Privacy Decision-Making: A Study on Cookie Acceptance

Directory of Open Access Journals (Sweden)

Lynne Margaret Coventry

2016-09-01

Full Text Available Despite their best intentions, people struggle with the realities of privacy protection and will often sacrifice privacy for convenience in their online activities. Individuals show systematic, personality dependent differences in their privacy decision making, which makes it interesting for those who seek to design ‘nudges’ designed to manipulate privacy behaviors. We explore such effects in a cookie decision task. Two hundred and ninety participants were given an incidental website review task that masked the true aim of the study. At the task outset, they were asked whether they wanted to accept a cookie in a message that either contained a social framing ’nudge’ (they were told that either a majority or a minority of users like themselves had accepted the cookie or contained no information about social norms (control. At the end of the task, participants were asked to complete a range of personality assessments (impulsivity, risk-taking, willingness to self-disclose and sociability. We found social framing to be an effective behavioral nudge, reducing cookie acceptance in the minority social norm condition. Further, we found personality effects such that those scoring highly on risk-taking and impulsivity were significantly more likely to accept the cookie. Finally, we found that the application of a social nudge could attenuate the personality effects of impulsivity and risk-taking. We explore the implications for those working in the privacy-by-design space.

Personality and Social Framing in Privacy Decision-Making: A Study on Cookie Acceptance

Science.gov (United States)

Coventry, Lynne M.; Jeske, Debora; Blythe, John M.; Turland, James; Briggs, Pam

2016-01-01

Despite their best intentions, people struggle with the realities of privacy protection and will often sacrifice privacy for convenience in their online activities. Individuals show systematic, personality dependent differences in their privacy decision making, which makes it interesting for those who seek to design ‘nudges’ designed to manipulate privacy behaviors. We explore such effects in a cookie decision task. Two hundred and ninety participants were given an incidental website review task that masked the true aim of the study. At the task outset, they were asked whether they wanted to accept a cookie in a message that either contained a social framing ‘nudge’ (they were told that either a majority or a minority of users like themselves had accepted the cookie) or contained no information about social norms (control). At the end of the task, participants were asked to complete a range of personality assessments (impulsivity, risk-taking, willingness to self-disclose and sociability). We found social framing to be an effective behavioral nudge, reducing cookie acceptance in the minority social norm condition. Further, we found personality effects in that those scoring highly on risk-taking and impulsivity were significantly more likely to accept the cookie. Finally, we found that the application of a social nudge could attenuate the personality effects of impulsivity and risk-taking. We explore the implications for those working in the privacy-by-design space. PMID:27656157

Influence of watermelon seed protein concentrates on dough handling, textural and sensory properties of cookies.

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Wani, Ali Abas; Sogi, D S; Singh, Preeti; Khatkar, B S

2015-04-01

Fruit processing wastes contain numerous by products of potential use in food & allied industry. Watermelon seeds represent a major by-product of the processing waste and contain high amount of nutritional proteins. Protein rich cereal based products are in demand due to their health promoting benefits. With this aim, wheat flour was fortified with watermelon seed protein concentrates (2.5 %, 5 %, 7.5 % and 10 % levels) to prepare cookies with desirable physical, nutritional, and textural and sensory properties. Substitution levels of 5 % and 10 % significantly (p ≤ 0.05) increased the dough stability and mixing tolerance index, however pasting properties and dough extensibility decreased considerably above 5 % substitution levels. Cookie fracture force (kg) increased significantly (p ≤ 0.05) above 5 % fortification levels. Cookie spread factor (W/T) increased from 2.5 % to 7.5 % fortification levels, further increase showed negative impact. Sensory scores of the cookies showed that protein concentrate may be added up to 7.5 % fortification levels. This study revealed that watermelon protein concentrates can be fortified with protein concentrates upto 5-7.5 % levels in cookies to improve their protein quality.

Teaching Quality Control with Chocolate Chip Cookies

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Baker, Ardith

2014-01-01

Chocolate chip cookies are used to illustrate the importance and effectiveness of control charts in Statistical Process Control. By counting the number of chocolate chips, creating the spreadsheet, calculating the control limits and graphing the control charts, the student becomes actively engaged in the learning process. In addition, examining…

Formulation and physicochemical and sensorial evaluation of biscuit-type cookies supplemented with fruit powders.

Science.gov (United States)

Uchoa, Ana Maria Athayde; Correia da Costa, José Maria; Maia, Geraldo Arraes; Meira, Tatyane Ribeiro; Sousa, Paulo Henrrique Machado; Montenegro Brasil, Isabella

2009-06-01

Cashew apple and guava residues from fruit juice industry were prepared as dehydrated fruit powders and used at different levels of wheat flour substitution for cookies formulations. The effects of guava and cashew apple fruit powders supplementation on physicochemical and sensorial characteristics of the cookies were evaluated. The pH, fibre and protein content were significantly affected. Biscuits with 15 g and 20 g/100g cashew apple and guava fruit powders showed the highest scores for sensorial attributes, respectively. The supplementation seems to be suited for wheat flour substitution and it is possible to obtain cookies with value-added food ingredient within the standards.

Novel cookie-with-chocolate carbon dots displaying extremely acidophilic high luminescence

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Lu, Siyu; Zhao, Xiaohuan; Zhu, Shoujun; Song, Yubin; Yang, Bai

2014-10-01

A fluorescent carbon dot with a cookie-with-chocolate film structure (about 5 × 5 μm2) showed a high fluorescence quantum yield (61.12%) at low pH. It was hydrothermally synthesized from l-serine and l-tryptophan. The formation mechanism of the film with carbon dots (CDs) was investigated. The film structure was formed by hydrogen bonding and π-π stacking interactions between aromatic rings. The strong blue fluorescence of the CDs increased under strong acidic conditions owing to the changes in the N-groups. These cookie-like CDs are attractive for their potential use as effective fluorescent probes for the sensitive detection of aqueous H+ and Fe3+.A fluorescent carbon dot with a cookie-with-chocolate film structure (about 5 × 5 μm2) showed a high fluorescence quantum yield (61.12%) at low pH. It was hydrothermally synthesized from l-serine and l-tryptophan. The formation mechanism of the film with carbon dots (CDs) was investigated. The film structure was formed by hydrogen bonding and π-π stacking interactions between aromatic rings. The strong blue fluorescence of the CDs increased under strong acidic conditions owing to the changes in the N-groups. These cookie-like CDs are attractive for their potential use as effective fluorescent probes for the sensitive detection of aqueous H+ and Fe3+. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03965c

Effects of ingredients of Korean brown rice cookies on attenuation of cholesterol level and oxidative stress in high-fat diet-fed mice.

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Hong, Sun Hee; Kim, Mijeong; Woo, Minji; Song, Yeong Ok

2017-10-01

Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik , was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase ( P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group ( P < 0.05). In addition, nuclear factor-kappaB (NF-κB) expression in the GBRD group was significantly lower than that in the RCD group. GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and

Analysis, distribution, and dietary exposure of glyoxal and methylglyoxal in cookies and their relationship with other heat-induced contaminants.

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Arribas-Lorenzo, Gema; Morales, Francisco J

2010-03-10

Thermal processing of food leads to the formation of dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO), which are potentially harmful because they are precursors of advanced glycation end products (AGEs). GO and MGO formation was examined during the baking process of cookies as cookies are a widely distributed food commodity in Western diets. GO and MGO were chromatographically analyzed after employment of an improved method of derivatization with orthophenylenediamine to produce stable quinoxaline derivatives. Sample extraction, cleanup, and chromatographic conditions were evaluated to provide an in-house validated procedure for GO and MGO analysis in cookies. Quantification limits were set at 1.5 and 2 mg/kg for GO and MGO, respectively, with an average recovery of 103% and a calculated precision lower than 7%. Studies were carried out both on laboratory-scale cookies under controlled conditions and on commercial samples as well. GO and MGO values in commercial cookies ranged from 4.8 to 26.0 mg/kg and from 3.7 to 81.4 mg/kg, respectively. Commercial cookies made from ammonium bicarbonate and fructose showed the highest levels of MGO. Dicarbonyls were rapidly formed on the upper side of the cookie regardless of the shape or thickness of the samples, confirming there was a surface effect. Under controlled baking conditions, the formations of GO and MGO were linearly correlated with baking time. MGO formation was related with acrylamide, a heat-processing contaminant, in commercial cookies, but this relationship was not observed for 5-hydroxymethylfurfural. Dietary exposure of the Spanish population to GO and MGO from cookies was estimated to be 213 and 216 microg/person/day, respectively.

Acceptability of Canistel (Lacuma Nervosa A.DC Fruit Flour in Making Cookies

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Delia A. Paragados

2014-02-01

Full Text Available This experimental research determined the acceptability in terms of appearance, aroma, texture, flavor and general acceptability of canistel (Lacuma nervosa A. DC fruit flour in different proportions in making cookies. This study was conducted in December 2011 at West Visayas State University – Calinog Campus, Calinog, Iloilo. Five treatments were used in the study – four of them utilized canistel fruit flour at various proportions and one treatment was used as the control group which utilized all purpose flour. The respondents of the study were the 15 faculty and staff, 15 Food Technology and BSHRM students of WVSU - Calinog Campus, and 15 housewives at Brgy. Simsiman, Calinog, Iloilo who were selected through purposive sampling. The respondents evaluated the finished products using a modified sensory evaluation score sheet based on Five Point Hedonic Scale. There were five treatments replicated three times. The statistical tools used were the means, standard deviation, One – Way Analysis of Variance, and the LSD. The .01 alpha level was used as the criterion for acceptance or rejection of the null hypotheses. The study revealed that cookies prepared using all treatments were “liked very much” in terms of appearance, aroma, texture, flavor and general acceptability. While cookies with 100% all - purpose flour were liked moderately by the evaluators. These results led to the conclusion that there is a significant difference that existed in the level of acceptability of canistel fruit flour in making cookies in terms of aroma, texture, flavor and general acceptability, therefore the null hypothesis is rejected. However, no significant difference in the level of acceptability of canistel fruit flour in making cookies in terms of appearance, therefore the null hypothesis is accepted.

Degree of roasting of carob flour affecting the properties of gluten-free cakes and cookies.

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Román, Laura; González, Ana; Espina, Teresa; Gómez, Manuel

2017-06-01

Carob flour is a product rich in fibre obtained from by-products of the locust bean gum extraction processing. The flour is commercialised with different degrees of roasting in order to improve its organoleptic characteristics. In this study, carob flour with three different roasting degrees was used to replace rice flour (15%) in gluten-free cakes and cookies. The influence of this replacement was studied on the psychochemical characteristics and acceptability of the final products. The incorporation of carob flour increased the viscosity of cake batters and increased the solid elastic-like behaviour of the cookie doughs, indicating a stronger interaction among the formula ingredients. The inclusion of carob flour, with a low time of roasting, did not lead to any significant differences in the specific volume and hardness of the cakes, but reduced cake staling and the thickness and width of the cookies. Darker colours were obtained when carob flour was incorporated into the product. The acceptability of cakes was only reduced with the addition of highly roasted carob flour, while in the case of cookies there was a decline in the acceptability of all carob flour cookies, which was mostly perceived with the highest roasting degree, something mainly attributed to the bitter taste of the products.

Acidulant and oven type affect total anthocyanin content of blue corn cookies.

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Li, Jian; Walker, Chuck E; Faubion, Jon M

2011-01-15

Anthocyanins, pink to purple water-soluble flavonoids, are naturally occurring pigments with claimed health benefits. However, they are sensitive to degradation by high pH, light and temperature. Blue corn (maize) contains high levels of anthocyanins. Cookies are popular snacks and might serve as a vehicle to deliver antioxidants. A cookie formula with a high level of blue corn was developed with added acidulents and baked in ovens with different heat transfer coefficients. The best whole-grain blue corn flour/wheat pastry flour ratio (80:20 w/w), guar gum level (10 g kg(-1), flour weight basis) and water level (215 g kg(-1), flour weight basis) were determined based on response surface methodology analysis. The interactions of citric and lactic acids and glucono-δ-lactone with three oven types having different heat transfer coefficients (impingement oven 179 °C/4 min, reel oven 204 °C/10 min and convection oven 182 °C/4 min) influenced the total anthocyanin content (TAC) remaining in blue corn-containing cookies after baking. Cookies baked with citric acid in the convection oven retained the maximum TAC (227 ± 3 mg kg(-1)). By baking rapidly at lower temperatures and adding acidulents, it may be possible to increase residual natural source antioxidants in baked foods. Copyright © 2010 Society of Chemical Industry.

Nutritional and sensory characteristics of gluten-free quinoa (Chenopodium quinoa Willd)-based cookies development using an experimental mixture design.

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Brito, Isabelle L; de Souza, Evandro Leite; Felex, Suênia Samara Santos; Madruga, Marta Suely; Yamashita, Fábio; Magnani, Marciane

2015-09-01

The aim of this study was to develop a gluten-free formulation of quinoa (Chenopodium quinoa Willd.)-based cookies using experimental design of mixture to optimize a ternary mixture of quinoa flour, quinoa flakes and corn starch for parameters of colour, specific volume and hardness. Nutritional and sensory aspects of the optimized formulation were also assessed. Corn starch had a positive effect on the lightness of the cookies, but increased amounts of quinoa flour and quinoa flakes in the mixture resulted in darker product. Quinoa flour showed a negative effect on the specific volume, producing less bulky cookies, and quinoa flour and quinoa flakes had a positive synergistic effect on the hardness of the cookies. According the results and considering the desirability profile for colour, hardness and specific volume in gluten-free cookies, the optimized formulation contains 30 % quinoa flour, 25 % quinoa flakes and 45 % corn starch. The quinoa-based cookie obtained was characterized as a product rich in dietary fibre, a good source of essential amino acids, linolenic acid and minerals, with good sensory acceptability. These findings reports for the first time the application of quinoa processed as flour and flakes in mixture with corn starch as an alternative ingredient for formulations of gluten-free cookies-type biscuits.

Karakteristik Amilografi Tepung Sorgum Fermentasi Dan Aplikasinya Pada Produk Cake Dan Cookies Sorgum

OpenAIRE

Setiarto, Raden Haryo Bimo; Widhyastuti, Nunuk; Saskiawan, Iwan

2017-01-01

This study aims to investigate the characteristics of fermented sorghum flour amylograph and organoleptic test of the product cake and cookies from fermented sorghum flour. Production of sorghum flour was made with four variations of treatments, ie: control (without fermentation), solid fermentation, liquid fermentation, mixture fermentation (solid and liquid). Amylograph profile analyzes the four samples of sorghum flour was conducted with Viscograph Brabender. In the manufacture of cookies ...

The Benefits, and Fear, of Cookie Technology

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Goldsborough, Reid

2004-01-01

"Cookies" are tiny Web browser helpers and are an example of how the useful can get tossed in with the dangerous through the near hysteria brought about by the real threats of computer viruses, hacking, spyware, spam and phishing. This article briefly discusses antispyware legislation by Congress and the pros and cons of past and future…

Development of cookies made with cocoyam, fermented sorghum and germinated pigeon pea flour blends using response surface methodology.

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Okpala, Laura C; Okoli, Eric C

2014-10-01

Cookies were produced from blends of cocoyam, fermented sorghum and germinated pigeon pea flours. The study was carried out to evaluate the effects of varying the proportions of these components on the sensory and protein quality of the cookies. The sensory attributes studied were colour, taste, texture, crispness and general acceptability while the protein quality indices were biological value (BV) and net protein utilization (NPU). Mixture response surface methodology was used to model the sensory and protein quality with single, binary and ternary combinations of germinated pigeon pea, fermented sorghum and cocoyam flours. Results showed that BV and NPU of most of the cookies were above minimum acceptable levels. With the exception of cookies containing high levels of pigeon pea flour, cookies had acceptable sensory scores. Increase in pigeon pea flour resulted in increase in the BV and NPU. Regression equations suggested that the ternary blends produced the highest increase in all the sensory attributes (with the exception of colour).

Characterization of cookies made from wheat flour blended with buckwheat flour and effect on antioxidant properties.

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Jan, Ulfat; Gani, Adil; Ahmad, Mudasir; Shah, Umar; Baba, Waqas N; Masoodi, F A; Maqsood, Sajid; Gani, Asir; Wani, Idress Ahmed; Wani, S M

2015-10-01

Buckwheat flour was incorporated into wheat flour at different levels (0, 20, 40, 60, 80, and 100 %) and the physicochemical, functional and antioxidant properties of the blended flour were studied. This study also investigated the effect of buckwheat on the retention of antioxidant properties of cookies during baking. The results showed significant variation in physicochemical and functional properties of the blended flour. The addition of buckwheat flour into wheat flour also increased the antioxidant properties of blended flour proportionally, but metal chelating properties decreased. The incorporation of buckwheat in wheat flour helped in better retention of antioxidant potential of cookies during baking process as buckwheat cookies (100 % buckwheat) showed greater percentage increase in antioxidant properties than control (100 % wheat). Quality characteristics of cookies such as hardness and spread ratio decreased, while as non-enzymatic browning (NEB) increased significantly with increase in the proportion of buckwheat flour in wheat flour. The Overall acceptability of cookies by sensory analysis was highest at 40 % level of blending. This study concluded that addition of buckwheat in wheat flour, may not only improve the physico-chemical and functional properties of the blended flour but may also enhance the nutraceutical potential of the product prepared from it.

Plantain peel - a potential source of antioxidant dietary fibre for developing functional cookies.

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Arun, K B; Persia, Florence; Aswathy, P S; Chandran, Janu; Sajeev, M S; Jayamurthy, P; Nisha, P

2015-10-01

Plantain cultivar Nendran is popular as a staple food in many parts of India and deep fried chips made from raw matured Nendran are one of the popular snack items in India. This study aims to utilize peel from Nendran variety- the main byproduct of banana chips industry- to develop high fibre cookies with enhanced bioactive content. Proximate analysis indicated that peels are rich in total dietary fibre (64.33 g/100 g), vitamins (Folic acid- 33.12 mg/100 g) and minerals (Potassium- 35.61 mg/100 g). Nendran Peel Flour (NPF) was extracted with hexane, ethyl acetate and methanol. Phenolic and flavonoid content was high for ethyl acetate extract (15.21 and 9.39 mg QE/g dry weight). Methanol extract was more potent in reducing Copper ion (2.36 μM TR/g dry weight) and scavenging NO (IC50-381.71 μg/mL). Ethyl acetate extract was capable of scavenging DPPH and hydroxyl radical. HPLC profiling showed presence of gallic acid, protocatechuic acid, rutin hydrate and quercetin in ethyl acetate extract and gallic acid, chlorogenic acid and vanillic acid in methanol extract. Cookies prepared with NPF possess higher total dietary fibre content. There was a decrease in spread ratio, breaking strength and browning index of cookies as the percentage of NPF increased. NPF incorporation gradually increased the phenolic content from 4.36 to 5.28 mg GAE, compared to control cookie (3.21 mg GAE). DPPH scavenging activity also increased with increase in NPF. Hence NPF is a very good source of antioxidant dietary fibre and acceptable cookies can be produced by replacing wheat flour with 10 % NPF.

"Split Them!" Smaller Item Sizes of Cookies Lead to a Decrease in Energy Intake in Children

NARCIS (Netherlands)

Marchiori, David|info:eu-repo/dai/nl/376283718; Waroquier, Laurent; Klein, Olivier

Objective: Examine the influence of altering the size of snack food (ie, small vs large cookies) on short-term energy intake. Methods: First- and sixth-graders (n = 77) participated in a between-subjects experimental design. All participants were offered the same gram weight of cookies during an

Quality characteristics of bread and cookies enriched with debittered Moringa oleifera seed flour.

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Ogunsina, B S; Radha, C; Indrani, D

2011-03-01

The effects of replacing wheat flour with 0-15% debittered moringa seed (DBMS) flour on the dough rheology of wheat flour and physical, sensory and chemical properties of bread were studied. Incorporation of an increasing amount of DBMS from 0 to 15% decreased farinograph water absorption, dough stability, amylograph peak viscosity and overall quality of bread. The bread with 10% DBMS had a typical moringa seed taste and was acceptable. Addition of combination of additives improved the dough strength and quality of bread with 10% DBMS flour. Replacement of wheat flour with 10%, 20% and 30% DBMS grits was found to affect cookies quality. Cookies with 20% DBMS grits had the nutty taste of moringa seeds and were acceptable. Bread with 10% DBMS flour and cookies with 20% DBMS grits had more protein, iron and calcium. Incorporating moringa seeds in baked foods may be exploited as a means of boosting nutrition in Africa and Asia where malnutrition is prevalent.

Emotional and uncontrolled eating styles and chocolate chip cookie consumption. A controlled trial of the effects of positive mood enhancement.

Science.gov (United States)

Turner, Sally Ann; Luszczynska, Aleksandra; Warner, Lisa; Schwarzer, Ralf

2010-02-01

The study tested the effects of positive mood enhancement on chocolate chip cookie consumption in the context of emotional and uncontrolled eating styles. The relationship between emotional eating style and chocolate chip cookie intake was assumed to be mediated by uncontrolled eating style. Further, it was hypothesized that the effectiveness of the positive mood enhancement may be more salient among those who have effective control of their eating. In this experimental study, respondents (N=106, 70% women, aged 16-45 years old) were assigned by means of cluster randomization to the control or positive mood enhancement condition (a comedy movie clip). Compared to the control condition, positive mood enhancement resulted in consuming on average 53.86 kcal less. Relationships between emotional eating style and cookie intake were mediated by uncontrolled eating. Moderated mediation analysis indicated that the effect of a mediator (uncontrolled eating) on cookie intake was moderated by the group assignment. Positive mood enhancement resulted in eating on average 3.3 cookies less among individuals with a more controlled eating style. By contrast, among those who presented uncontrolled eating, positive mood enhancement led to consuming an average of 1.7 cookies more. 2009 Elsevier Ltd. All rights reserved.

Caracterização física, química e sensorial de cookies confeccionados com farinha de talo de couve (FTC e farinha de talo de espinafre (FTE ricas em fibra alimentar Phisical, chemical, and sensorial characterization of cookies made with kale stalk flour (KSF and spinach stalk flour (SSF rich in nourishing fiber

Directory of Open Access Journals (Sweden)

Ana Karina Mauro

2010-09-01

Full Text Available Objetivou-se utilizar Farinhas de Talos (FT na confecção de cookies. As farinhas foram obtidas a partir de talos de couve manteiga e espinafre desidratados. Confeccionaram-se 3 tipos de cookies por modificação da formulação padrão de sugar-sanap cookie, método 10-50D (AMERICAN..., 1995: cookie controle, cookie com 15% de FTC e com 15% de FTE. Realizou-se a composição centesimal nas FT segundo as metodologias descritas da AOAC (ASSOCIATION..., 1995, sendo as fibras alimentares analisadas pelo método de van Soest (1963. Nos cookies, procedeu-se às seguintes análises: peso, espessura, diâmetro, volume e densidade aparente segundo método 10-50D da AACC (AMERICAN..., 1995, acidez titulável e pH através da técnica do Instituto Adolfo Lutz (SÃO PAULO, 1985, rendimento e fator térmico. A composição centesimal dos cookies seguiu normas da AOAC (ASSOCIATION..., 1995 e, para aceitação dos experimentais, utilizou-se escala hedônica de 9 pontos. Constatou-se que as FT possuem baixa densidade energética e alto teor de fibra alimentar e cinzas. Os cookies experimentais apresentaram maior (p The objective of the study was to use Stalk Flours (SF to prepare cookies. The ST was made with dehydrated Kale Stalks (KSF and Spinach Stalks (SSF. Three kinds of cookies were prepared by modification of the sugar-snap cookie formula, 10-50D method (AMERICAN..., 1995: control cookie, cookie with 15% of KSF, and cookie with 15% of SSF. The centesimal composition was performed on the SF by the AOAC (ASSOCIATION..., 1995 and the nourishing fibers were prepared according to van Soest (1963. The following parameters were analyzed: weight, thickness, diameter, volume, and apparent density according to the 10-50D method of the AACC (AMERICAN..., 1995, titratable acidity and pH using the Adolfo Lutz Institute (2005 technique, and also revenue and caloric factor. The determination of the centesimal composition of the cookies followed the AOAC regulations

Tempeh flour as a substitute for soybean flour in coconut cookies

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Rodrigo Santos Leite

2013-12-01

Full Text Available The objective of this study was to prepare roasted and lyophilized tempeh flour with soybean cultivar BRS 267 to apply them in the formulation of coconut biscuits. The cookies produced with whole soy flour and mixed flour of soybean and tempeh were evaluated for proximate composition, fatty acid profile, and isoflavone aglycones in order to verify the effects of inoculation with the fungus Rhizopus oligosporus and those of the drying processes of roasting and lyophilization on the chemical characteristics of the final product. Sensory acceptance and purchase intention of the formulated products were also evaluated. The results indicate the maintenance of linolenic acid, which is important in the prevention of coronary diseases, and an increase in the aglycones levels when the tempeh flour was used. Lipids and proteins showed differences, and the sensory analyses demonstrated similarity between the cookies with satisfactory scores for aroma, flavor, texture, and overall acceptability for both samples. when compared to the control. Purchase intent was also positive for the lyophilized and toasted tempeh flours, thus enabling the use of the roasting process as a simple drying method, for processing tempeh and obtaining a flour rich in proteins and aglycones that can be used as a partial substitute for soy flour in cookies and other bakery products.

The influence of addition of dried tomato pomace on the physical and sensory properties of whole grain rye flour cookies

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Tomić Jelena M.

2016-01-01

Full Text Available One of the potential raw materials which could be used for production of food with added nutritional value is tomato pomace, a by-product from tomato processing. On the other hand, requirements of consumers for diverse food with potential for health benefits impose the need for creation of products made from different cereals. In this respect, the aim of this study was to evaluate the influence of addition of dried tomato pomace on the physical and sensory properties of whole grain rye flour cookies. The whole grain rye flour was substituted with tomato pomace powder in two levels (15% and 25% in the standard formulation of short-dough cookie. The quality of final products was evaluated by instrumental and sensory methods. The results clearly demonstrated that redness (+a* and yellowness (+b* were highly influenced by level of tomato pomace in the cookie formulations due to its content of carotenoid pigments. The spread factor of the cookies made with addition of tomato pomace powder was higher than the control sample. Hardness of the cookie samples decreased for approximately 50% for the cookie sample with 25% tomato pomace level substitution when compared with control sample. According to the results of sensory analysis, substitution level of 15% caused decrease of surface roughness, fracturability, and granularity, as well as increase of caramel flavour intensity. Substitution level of 25% caused higher degree of cookie softening and more pronounced tomato flavour.

Desenvolvimento de formulações de biscoitos tipo cookie contendo café Development of cookie formulations containing coffee

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Melissa de Abreu Andrade Rodrigues

2007-03-01

Full Text Available Este trabalho teve como objetivo desenvolver formulações de biscoitos tipo cookie contendo café. Desenvolveram-se três formulações com inserção de café como: bebida tipo expresso, café solúvel e café torrado e moído, utilizando como base uma formulação americana adaptada aos ingredientes brasileiros e à inserção de café. A composição centésimal média (base seca foi: 7% umidade, 70% carboidratos, 8% proteínas, 21% gorduras e 1% minerais, com valor calórico médio de 499 kcal.100 g -1. A composição centesimal e o valor calórico observados foram similares a valores reportados para biscoitos cookie comercialmente disponíveis. A forma de inserção de café afetou as características sensoriais dos produtos, avaliados por metodologia descritiva de perfil de sabor e de textura. A Formulação 1 (bebida tipo expresso apresentou valores inferiores para a intensidade dos atributos referentes à presença de rachaduras, fragmentação, presença de pontos escuros, aroma de café e queimado. A Formulação 2 (café solúvel apresentou notas superiores de intensidade dos atributos de cor marrom, brilho, sabor amargo e de queimado, sabor residual de açúcar mascavo e crocância da borda e inferiores para concavidade. A Formulação 3 (café torrado e moído apresentou valores superiores para a presença de pontos escuros. As três formulações apresentaram notas satisfatórias e equivalentes de aceitação por crianças.The aim of the present study is to develop cookie formulations containing coffee. Three formulations were developed, each with a distinct way of adding coffee: espresso beverage, instant coffee and roasted coffee powder. The average proximate composition (dry basis of the formulations was 7% moisture, 70% carbohydrates, 8% protein, 21% fat and 1% minerals, resulting in an average caloric value of 499 kcal per 100 g product. Both the proximate composition and average caloric value were similar to values reported

Effects of fatty acids composition and microstructure properties of fats and oils on textural properties of dough and cookie quality.

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Devi, Amita; Khatkar, B S

2018-01-01

This study was carried out to investigate the effect of fatty acid composition and microstructure properties of fats and oils on the textural properties of cookie dough and quality attributes of cookies. Fatty acid composition and microstructure properties of six fats and oils (butter, hydrogenated fat, palm oil, coconut oil, groundnut oil, and sunflower oil) were analyzed. Sunflower oil was found to be the most unsaturated oil with 88.39% unsaturated fatty acid content. Coconut oil and palm oil differed from other fats and oils by having an appreciable amount of lauric acid (59.36%) and palmitic acid (42.14%), respectively. Microstructure size of all fats and oils ranged from 1 to 20 μm being the largest for coconut oil and the smallest for palm oil. In palm oil, small rod-shaped and randomly arranged microstructures were observed, whereas sunflower oil and groundnut oil possessed large, scattered ovule shaped microstructures. It was reported that sunflower oil produced the softest dough, the largest cookie spread and the hardest cookie texture, whereas hydrogenated fat produced the stiffest dough, the lowest spread and most tender cookies. Statistical analysis depicted that palmitic acid and oleic acid demonstrated a positive correlation with dough hardness. Linoleic acid exhibited positive link with cookie spread ratio (r = 0.836**) and breaking strength (r = 0.792**). Microstructure size showed a significant positive relationship with dough density (r = 0.792**), cookie density (r = 0.386*), spread ratio (r = 0.312*), and breaking strength (r = 0.303*).

CD 121 - cultivar with flour characteristics for cookie baking

OpenAIRE

Marchioro, Volmir Sergio; Franco, Francisco de Assis; Dalla Nora, Tatiane; Schuster, Ivan; Evangelista, Adriel; Lima, Fábio Junior Alcântara de; Polo, Mateus

2013-01-01

CD 121 is indicated for wheat regions with the classification Value for Cultivation and Use 1 and 2, in the states of PR, SC and RS. The cultivar is tolerant to leaf rust, has good agronomic traits, flour suited for cookie baking and an average grain yield of 3.622 kg ha-1.

CD 1805 - Wheat with flour characteristics for cookie baking

OpenAIRE

Franco, Francisco de Assis; Marchioro, Volmir Sergio; Schuster, Ivan; Polo, Mateus; Lima, Fábio Junior Alcântara de; Evangelista, Adriel; Montecelli, Tatiane Dalla Nora; Santos, Diego Augusto dos; Grave, Edson Luis

2016-01-01

Abstract CD 1805, indicated for the wheat growing in Regions 1, 2 and 3 in the states of Rio Grande do Sul, Santa Catarina and Paraná. The cultivar has quality standards for cookie production and high yield performance with a mean of 3899 kg ha-1, exceeding the controls by 4%.

Allergen sanitation in the food industry: a systematic industrial scale approach to reduce hazelnut cross-contamination of cookies.

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Röder, Martin; Baltruweit, Iris; Gruyters, Helwig; Ibach, Anja; Mücke, Ingo; Matissek, Reinhard; Vieths, Stefan; Holzhauser, Thomas

2010-09-01

Recently, we investigated the impact of shared equipment on cross-contamination of cookies at a pilot plant scale. Based on those findings, this study investigated the extent and subsequent sanitation of hazelnut cross-contamination (HNCC) of cookies at the industrial scale. Similarly, a product change from cookies with hazelnut ingredient to cookies without hazelnut was performed on standard equipment. HNCC in the hazelnut-free follow-up product was quantified by enzyme-linked immunosorbent assay for each production device and the applied cleaning procedure. All experiments were repeated in duplicate. The highest HNCC was found in concordance with previous studies after mere mechanical scraping: more than 1,000 mg of hazelnut protein per kg was quantified in the follow-up product after processing by a cookie machine. Additional cleaning with hot water decreased the HNCC irrespective of the processing device to levels at or below 1 mg of hazelnut protein per kg. Furthermore, raw materials for cookie production were monitored over a period of 24 months for unwanted preloads of hazelnut and peanut: hazelnut was quantified in 16% of the investigated raw materials as being between 0.26 and 90 mg/kg. Further critical control points at the industrial scale, where cross-contamination might occur, were identified but did not display noteworthy sources of cross-contamination. In conclusion, the quantitative monitoring of the cleaning efficiency at the industrial scale confirmed the procedure of manual scraping plus wet cleaning as a qualified sanitation procedure to effectively reduce the hazelnut protein cross-contamination down to a level at which severe hazelnut-related allergic reactions are unlikely to occur.

CD 1805 - Wheat with flour characteristics for cookie baking

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Francisco de Assis Franco

2016-03-01

Full Text Available CD 1805, indicated for the wheat growing in Regions 1, 2 and 3 in the states of Rio Grande do Sul, Santa Catarina and Paraná. The cultivar has quality standards for cookie production and high yield performance with a mean of 3899 kg ha-1, exceeding the controls by 4%.

CD 121 - Cultivar with flour characteristics for cookie baking

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Volmir Sergio Marchioro

2013-06-01

Full Text Available CD 121 is indicated for wheat regions with the classification Value for Cultivation and Use 1 and 2, in the states of PR,SC and RS. The cultivar is tolerant to leaf rust, has good agronomic traits, flour suited for cookie baking and an average grain yieldof 3.622 kg ha-1.

Functionality of Inulin as a Sucrose Replacer in Cookie Baking

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Inulin was evaluated as a sucrose replacer for healthy cookie production with benefits of low glycemic impact and prebiotic soluble fiber. Sucrose (as a reference) and three inulin products of different concentrations (as soluble fibers) were used to explore the effects of sugar-replacer type on so...

Oxidative stability of the lipid fraction in cookies – the EPR study

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Zawada Katarzyna

2015-07-01

Full Text Available Cookies are a group of convenient food products that are popular among consumers. They may contain high amounts of fats, which can be prone to oxidation. To retard the oxidative deterioration, synthetic and natural antioxidants may be added. Herb and spice extracts can be sources of natural biologically active substances with antioxidant activity. In this work, electron paramagnetic resonance spectroscopy was used to monitor the lipid oxidation in cookies with rosemary and thyme extracts subjected to the storage in elevated temperature. It was shown that thyme extract can be used as a natural antioxidant source for the preparation of bakery products, while the rosemary extract should be used with care in fat-rich products exposed to high temperatures.

Avaliação tecnológica de biscoitos tipo cookie com variações nos teores de lipídio e de açúcar Technological evaluation of cookies with lipid and sugar content variations

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Kessiane Silva de Moraes

2010-05-01

Full Text Available A proposta deste trabalho foi investigar o efeito da concentração de açúcar e de lipídio na qualidade tecnológica de biscoitos tipo cookie. Para estudar o efeito das variáveis independentes nas respostas, foi realizado delineamento fatorial 2² (quatro ensaios fatoriais com três repetições no ponto central, totalizando sete ensaios. Os parâmetros avaliados foram massa e diâmetro antes e após o forneamento, espessura, fator de expansão, volume específico e força de quebra dos biscoitos. Foi observado que, em concentrações de açúcar entre 44 e 57% e em concentrações de gordura entre 30 e 38%, foram obtidos os maiores diâmetros depois do forneamento e biscoitos com cor amarela mais intensa. Biscoitos com elevadas concentrações de açúcar apresentaram maior fator de expansão e biscoitos com elevadas concentrações de gordura apresentaram menor força de quebra.The objective of this study was to investigate the effect of sugar and lipid concentrations on the technological quality of cookies. To study the effect of independent variables on the answers, a factorial design 2² (four factorial assay with three repetitions at the central point, totalizing seven tests, was developed. The parameters evaluated were mass and diameter before and after baking, thickness, expansion factor, specific volume, and break force. It was observed that for sugar concentrations between 44 and 57% and fat concentrations between 30 and 38%, cookies with more intense yellow color and the largest diameter after baking were obtained. Cookies with high sugar concentrations presented larger expansion factor, and cookies with high fat concentrations presented smaller break force.

The influence of baking time and temperature on characteristics of gluten free cookies enriched with blueberry pomace

OpenAIRE

Šarić Bojana M.; Nedeljković Nataša M.; Šimurina Olivera D.; Pestorić Mladenka V.; Kos Jovana J.; Mandić Anamarija I.; Sakač Marijana B.; Šarić Ljubiša Ć.; Psodorov Đorđe B.; Mišan Aleksandra Č.

2014-01-01

Blueberry pomace, by-product of juice production, was processed into a new food ingredient by drying and grinding and used for a new gluten-free cookies' formulation, with the aim of improving nutritional profile and antioxidant capacity. Since duration and temperature at which dough is thermally treated during baking highly influence the quality of a baked product, the objective of this work was to optimise the baking conditions in order to obtain the best technological quality of the cookie...

Economic Evaluation of Cookie made from blend of Brewers′ Spent Grain (BSG, Groundnut cake and Sorghum Flour

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Olawoye Babatunde

2017-08-01

Full Text Available Bakery and pastry products such as cookies are usually produced from wheat flour and as such contribute to high foreign exchange for tropical countries where such cereal is not cultivated. In view of this, we evaluated the engineering economics for the utilization of dried brewers′ spent grain, groundnut cake and sorghum flour in the industrial production of cookies. The production was based on the assumption that the cash flow was uniform over the plant life (i.e. 10 years with no salvage value. The equipment required for the production process was identified and estimates obtained from equipment manufactures. The production of the cookies was based on constant mass flow rate of 90 packets/min. The effects of uncertainties on cookie production were evaluated by varying the operation days (330, 300 and 250 days and also by varying the price of some key variables required for the production processes. The results indicate that the capital cost (fixed and working capital and the annual production cost (APC were US$1.39×106 and US$10.08×106/year, respectively. The after tax annual revenue was US$1.63×106/yr. The return on investment (ROI, single payback period (SPBP, discounted payback period, gross margin and internal rate of return (IRR of the plant were 63%, 1.58 years, 2.08 years, 23% and 77.52%, respectively. The result also showed that the production plant is feasible and could be operated for 330, 300 and 250 days. The difference between operation times lies in the profitability, which decreases as the number of days reduces. Based on the result of this analysis, brewers’ spent grain, groundnut cake, and sorghum flour can be utilized in industrial production of cookies with guaranteed profitability.

The development of low glycemic index cookie bars from foxtail millet (Setaria italica), arrowroot (Maranta arundinacea) flour, and kidney beans (Phaseolus vulgaris).

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Lestari, Lily Arsanti; Huriyati, Emy; Marsono, Yustinus

2017-05-01

Wholegrain foods are becoming increasingly popular as a high fiber dietary supplement recommended for people with diabetes. In Indonesia, the incidence of diabetes mellitus has almost doubled recently and poses a significant health risk with the high prevalence of obesity and cardiovascular diseases. The present research aimed to develop cookie bars from foxtail millet, arrowroot flour, and kidney beans. The physical, chemical, and sensory properties were evaluated by selecting the best formula to test the glycemic index. Three formulae of cookie bars, which had different percentages of foxtail millet, kidney beans, and arrowroot flour were evaluated. The results showed that the three formulae (F1, F2, F3) had °Hue values of 53.77, 58.46, and 58.31, and breaking force of 8.37, 10.12, and 5.87 N, respectively. While all other nutritional content were significantly different between formulae, the total crude fat was not. The F2 cookie bar was selected and evaluated for the glycemic index because it has the best sensory properties, lowest total sugar and available carbohydrate content. F2 cookie bars that contain 15% foxtail millet, 15% arrowroot flour, and 30% of kidney beans have a glycemic index of 37.6 hence it could be classified as a low glycemic index cookie bar. In conclusion, our findings indicated that F2 cookie bars can be further developed as a suitable diabetic food since it has the best physico-chemical properties, sensory properties, and low glycemic index.

Study on evaluation of starch, dietary fiber and mineral composition of cookies developed from 12 sorghum cultivars.

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Rao, B Dayakar; Kulkarni, Dhanashri B; C, Kavitha

2018-01-01

The study aimed to identify best cultivars suitable for sorghum cookies accordingly nutrient and mineral compositions were evaluated. Protein and fat content of cookies were ranged from 5.89±0.04 to 8.27±0.21% and 21.03±0.01 to 23.08±0.03% respectively. The starch content of cookie ranged between 47.06±0.01 and 42.15±0.03% and dietary fiber was reported highest in CSH14 (9.27±0.01%). The highest Mg (56.24±0.03mg/100g) P (255.54±0.03mg/100g), and K (124.26±0.02mg/100g) content were found in C43 cultivar. CSV18R was reported highest iron content (1.23±0.01mg/100g). The sensory scores for overall acceptability of cookies were highest in CSH23, CSH13R and CSV18R cultivars which are rich in dietary fiber and minerals. Normally the hybrids are high yielders and the grain price/qt is 20% lower than varieties. It is implied the raw material costs of two identified cultivars (CSH23 & CSH13R) would help the industry to reduce overall cost of production and offer a better profit margins over the varieties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationships of flour solvent retention capacity, secondary structure and rheological properties with the cookie making characteristics of wheat cultivars.

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Kaur, Amritpal; Singh, Narpinder; Kaur, Seeratpreet; Ahlawat, Arvind Kumar; Singh, Anju Mahendru

2014-09-01

The relationships of grain, flour solvent retention capacity (SRC) and dough rheological properties with the cookie making properties of wheat cultivars were evaluated. Cultivars with higher proportion of intermolecular-β-sheets+antiparallel β sheets and lower α-helix had greater gluten strength. The grain weight and diameter positively correlated with the proportion of fine particles and the cookie spread factor (SF) and negatively to the grain hardness (GH) and Na2CO3 SRC. The SF was higher in the flour with a higher amount of fine particle and with a lower Na2CO3 SRC and dough stability (DS). The breaking strength (BS) of cookies was positively correlated to lactic acid (LA) SRC, DS, peak time, sedimentation value (SV), G' and G″. Na2CO3 SRC and GH were strongly correlated. The gluten performance index showed a strong positive correlation with SV, DS, G' and G″. The water absorption had a significant positive correlation with sucrose SRC and LASRC. Cultivars with higher GH produced higher amount of coarse particles in flours that had higher Na2CO3 SRC and lower cookie SF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Not enough fruit and vegetables or too many cookies, candies, salty snacks, and soft drinks?

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Cohen, Deborah A; Sturm, Roland; Scott, Molly; Farley, Thomas A; Bluthenthal, Ricky

2010-01-01

There are many contributors to obesity, including excess consumption of "discretionary calories" (foods high in sugar and fat and low in essential nutrients), lack of fruit/vegetable consumption, and insufficient physical activity. This study contrasted physical activity, fruit/vegetable consumption, and discretionary calorie consumption from selected foods relative to the 2005 dietary guidelines. We conducted a cross-sectional survey in 228 urban census tracts in Los Angeles County (LAC) and Southern Louisiana (SL) and estimated calories in the past 24 hours from fruit, vegetables, cookies, candy, salty snacks, sweetened soda, and alcohol among 2,767 participants. The population-weighted mean daily intake of calories from candy, cookies, salty snacks, soda, and alcohol was 438 in LAC and 617 in SL. Alcohol comprised a small portion of the calories consumed. Reported discretionary calorie consumption from a small set of items exceeded guidelines by more than 60% in LAC and 120% in SL. In contrast, the mean consumption of fruit and vegetables fell 10% short in LAC and 20% in SL. There was significant heterogeneity in consumption of cookies, candy, salty snacks, and soda across income, gender, and race. The overconsumption of discretionary calories was much greater than the underconsumption of fruit and vegetables. This finding suggests that unless the excessive consumption of salty snacks, cookies, candy, and sugar-sweetened beverages is curtailed, other interventions focusing on increasing physical activity and fruit and vegetable consumption will have a limited impact on obesity control. It may be politically more expedient to promote an increase in consumption of healthy items rather than a decrease in consumption of unhealthy items, but it may be far less effective.

Shelf-life of almond pastry cookies with different types of packaging and levels of temperature.

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Romeo, F V; De Luca, S; Piscopo, A; Santisi, V; Poiana, M

2010-06-01

Almond pastries are typical cookies of the south of Italy. Introduction of new packaging for this kind of cookies requires shelf-life assessments. This study, related to different types of packaging under various storage conditions of time and temperature, identifies critical parameters, as color and texture, to track during storage studies and to extend the shelf-life. The cookies were packed in three different ways and stored at two different temperatures. The pastries were separately stored: (1) in polyvinylchloride film; (2) in aluminum foil (ALL); (3) with modified atmosphere (MAP) in plastic vessels sealed into a polyamide/ polyethylene film; and (4) in vessels without any polymeric film. The storage temperatures were 20 and 30 °C. Evolution of texture, water activity, dry matter and color was assessed. Texture was evaluated by a texture analyzer with a puncturing test. Indices for hardening were the area under the curve (N × mm) up to 10 mm of distance, and the maximum force (N) corresponding to the crust fracture. The best results were obtained with ALL packaging and MAP condition, and above all, in all the trials a temperature of 30 °C reduced the crust hardness.

Pengaruh Penggunaan Talas (Xanthosoma sagittifolium Terhadap Mutu dan Tingkat Penerimaan Panelis pada Produk Roti, Pastel, Pancake, Cookies, dan Bubur Talas

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Wilsa Hermianti

2016-06-01

Full Text Available Kimpul taro (Xanthosoma sagittifolium contains high enough of starch and fibers so that it can function as a non-rice food carbohydrates source. Previous research was done a research about taro block process technology (Hermianti et al., 2010. In this study, taro blocks was used for making of various wet food, semi-wet and dry food products such as bread, pies, cookies, pancakes, and taro porridge by substituting wheat flour and rice flour. The research was aimed to find out the composition of the appropriate use of taro block in making of various food products with a good quality and preferred. Bread, pies, and cookies were made with percentage of taro block 0% (control/without taro block, 25%, 50%, and 75%, whereas for pancakes with formula of taro block 0% (control/without taro block , 30%, 50%, 100%. Porridge was made to subtitute rice flour with percentage of taro block 0% (control/without taro block, 30%, 50%, and 100%. The chemical analysis of taro block was done on several parameter included moisture content, ash content, starch, and protein, while for processed food products were conducted the organoleptic test (color, aroma, taste, and texture based on the panelists acceptance level. The most products of taro cookies and taro bread preferred by panelists were analyzed the fat content, protein, carbohydrates and calories and storability for dry food products (cookies. The results showed that taro block moisture content 12.40%, ash content 1.12%, starch content 73.37%, amylose 2.88%, amylopectin 70.49%, and  protein 3.4%. The organoleptic test with optimal results and preferably were bread and pastel with the use of taro 25%, cookies with the use of taro 50%, taro pancake formula with 50%  taro block,  and porridge with usage of taro block 30%.ABSTRAKTalas kimpul (Xanthosoma sagittifolium mengandung karbohidrat dan serat yang tinggi  sehingga dapat berfungsi  sebagai sumber bahan pangan karbohidrat. Penelitian terdahulu telah

Exploitation of alfalfa seed (Medicago sativa L.) flour into gluten-free rice cookies: Nutritional, antioxidant and quality characteristics.

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Giuberti, Gianluca; Rocchetti, Gabriele; Sigolo, Samantha; Fortunati, Paola; Lucini, Luigi; Gallo, Antonio

2018-01-15

In an effort to increase the nutritional value of common gluten-free (GF) cereal-based foods, GF cookies using alfalfa seed flour (ASF), at different substitution levels to common rice flour (0% as control, 15%, 30% and 45% w/w), were produced. Crude protein, total dietary fibre, total polyunsaturated, total n-3 and n-6 fatty acid contents increased linearly (p<0.05) by raising the substitution levels of rice with ASF. The hardness, the total phenolic content, the in vitro antioxidant capacity and the resistant starch increased linearly (p<0.05), whereas the starch hydrolysis index decreased linearly (p<0.05) by raising the substitution levels of rice flour with ASF. Despite the fact that ASF-substituted GF cookies had inferior sensory attributes compared to the control, the score given by the panellists remained at fairly good levels for all tested parameters, showing acceptability of the substituted GF cookies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biscoitos produzidos com farinha de banana: avaliações química, física e sensorial Cookies produced with banana meal: chemical, physical andsensorial evaluation

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Luiz Henrique Fasolin

2007-09-01

Full Text Available Este trabalho teve como objetivo avaliar o aproveitamento da farinha de banana verde (FBV (Musa (grupo AAA ‘Cavendish anã’ na produção de biscoitos tipo cookies. Foram produzidos biscoitos com substituição parcial da farinha de trigo por FBV na proporção de 10, 20 e 30%, e biscoitos Padrão sem FBV. Os biscoitos foram avaliados quanto à composição química, características físicas (diâmetro, espessura e peso e grau de aceitação. O teste de aceitação dos biscoitos indicou não haver diferença significativa entre as diferentes formulações e o padrão, com exceção para o biscoito tipo III que apresentou menor aceitação (p The objective of this work was to evaluate the use of unripe banana meal (UBM (Musa (AAA group ‘Dwarf Cavendish’ in the production of cookies. Cookies were produced substituting 10, 20 and 30% of the wheat flour for UBM, as well as standard cookies without UBM. The chemical compositions, physical features (weight, diameter and thickness and sensorial characteristics of the cookies were evaluated. A cookie acceptance trial was conducted, which revealed no significant difference between the formulations containing UBM and the standard, except for the type III cookie, which was less well accepted (p < 0.05 by children. The chemical composition of the cookies did not differ significantly from the standpoint of moisture and total lipids. The most important differences were found in the starch, total reducing sugars and mineral salts content. The main differences in the cookies’ physical characteristics were their diameters after baking, indicating that UBM altered the properties of the wheat flour. Therefore, in view of the high nutritional value of the cookies containing banana meal, with no significant alteration of their physical and sensorial characteristics, the use of this meal as a partial substitute of wheat flour is viable and can be recommended in the preparation of alternative nutritionally

Evaluación física y química dE los rizomas dE guapo ( Maranta arundinacea y dE gallEtas dulcEs prEparadas con su harina I physical and chEmical Evaluation of guapo ( Maranta arundinacea rhizomEs and swEEt cookiEs madE with its flou

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Ana Teresa Ciarfella

2018-05-01

Full Text Available The use of flour from unconventional sources contributes to maintaining and adding value to crops currently little known. Weight, length, thickness, edible portion, flour yield from guapo ( Maranta arundinacea rhizomes were studied; sweet cookies were prepared with its flour: 100% guapo flour (GHG, 100% wheat flour (GHT and a 50:50 mixture of wheat flour and guapo flour (GHTG. Proximate composition and color of flours and cookies were determined; in addition, spreading factor and level of sensory acceptance were determined on the cookies. Rhizomes had a weight, length and thickness averages of 116.28 ± 56.32 g, 10,83 ± 2.18 cm and 4.50 ± 0.79 cm, respectively; the yield in edible portion and flour was 92.79 ± 4.40% and 47.08%, respectively. Compared to wheat flour, the guapo had lower protein and fat content and higher ash content ( p 0.05; color difference was 3.04 (GHG and 0.95 (GHTG regarding the GHT. The acceptability of the sweet cookies was similar ( p > 0.05 in color, odor, texture and flavor attributes. This study shows that guapo flour can replace wheat flour for making sweet cookies well accepted by consumers

Inactivation of Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes in ready-to-bake cookie dough by gamma and electron beam irradiation.

Science.gov (United States)

Jeong, Seul-Gi; Kang, Dong-Hyun

2017-06-01

This study was conducted to investigate the efficacy of gamma and electron beam irradiation to inactivate foodborne pathogens in ready-to-bake cookie dough and to determine the effect on quality by measuring color and texture changes. Cookie dough inoculated with Escherichia coli O157:H7, Salmonella Typhimurium, or Listeria monocytogenes was subjected to gamma and electron beam irradiation, with doses ranging from 0 to 3 kGy. As the radiation dose increased, the inactivation effect increased among all tested pathogens. After 3.0 kGy of gamma and electron beam irradiation, numbers of inoculated pathogens were reduced to below the detection limit (1 log CFU/g). The D 10 -values of E. coli O157:H7, S. Typhimurium, and L. monocytogenes in cookie dough treated with gamma rays were 0.53, 0.51, and 0.71 kGy, respectively, which were similar to those treated by electron beam with the same dose. Based on the D 10 -value of pathogens in cookie dough, L. monocytogenes showed more resistance to both treatments than did E. coli O157:H7 and S. Typhimurium. Color values and textural characteristics of irradiated cookie dough were not significantly (P > 0.05) different from the control. These results suggest that irradiation can be applied to control pathogens in ready-to-bake cookie dough products without affecting quality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Formulation and Evaluation of Cookies Containing Germinated Pigeon Pea, Fermented Sorghum and Cocoyam Flour Blends using Mixture Response Surface Methodology

OpenAIRE

Laura C. Okpala; Eric C. Okoli

2011-01-01

Cookies were produced from blends of germinated pigeon pea, fermented sorghum and cocoyam flours. The study was carried out to evaluate the effects of varying the proportions of these components on the sensory and protein quality of the cookies. The sensory attributes studied were colour, taste, texture, crispiness and general acceptability while the protein quality indices were Biological Value (BV) and Net Protein Utilization (NPU). Mixture response surface methodology was used to model the...

[Use of algarrobo (Prosopis chilensis (Mol) Stuntz) flour as protein and dietary fiber source in cookies and fried chips manufacture].

Science.gov (United States)

Escobar, Berta; Estévez, Ana María; Fuentes, Carolina; Venegas, Daniela

2009-06-01

Limiting amino acids of the protein from chilean "algarrobo" are isoleucine, theronine and methionine/cyteine. Cereals and legume blends allow to improve the amino acid balance, since legume have more lysine, and cereals are richer in sulphur amino acids. Due to the nutritional interest of "algarrobo" cotyledons, the use of "algarrobo cotyledon" flour (ACF) in sweet and salty snack manufacture was evaluated. Cookies and fried salty chips with 0%, 10% and 20% ACF were prepared. Flours were analyzed for color, particle size, moisture, proximate composition, available lysine, and soluble, insoluble and total dietary fiber. Cookies and chips were analyzed for the same characteristics (except for particle size); besides there were determined water activity, weight and size of the units, and also, the caloric value was computed. Sensory quality and acceptance of both products were evaluated. It is noticeable the high amount of protein, lipids, ash, crude fiber (63.6; 10.2; 4.3 and 4.2 g/100 g dmb, respectively), available lysine (62.4 mg/g protein) and total dietary fiber (24.2 g/100 g dmb) of ACF. Both, cookies and chips with ACF, showed a significant increase in the amount of protein, lipids, ash, crude fiber and, available lysine (from 15.5 to 19,3 and from 20.3 a 29.6 mg lisina/g protein, respectively), and total dietary fiber (from 1.39 to 2.80 and from 1.60 a 5.60 g/100 g dmb, respectively). All of the cookies trials were well accepted ("I like it very much"); chips with 10% of AFC showed the highest acceptance ("I like it"). It can be concluded that the use of ACF in cookies and chips manufacture increases the contribution of available lysine; their protein and dietary fiber content, improving the soluble/insoluble fiber ratio, without affect neither their physical nor their sensory acceptance.

Cookies, Coleslaw, and Stoops : The Influence of Dutch on the North American Languages

NARCIS (Netherlands)

Sijs, van der Nicoline

2009-01-01

Van Santa Claus (Sinterklaas) en zijn slee (sleigh) tot aan de dollar (vernoemd naar de daalder) en Yankees (Jan Kees), de Nederlandse taal is van grote invloed geweest op het Amerikaans-Engels. Yankees, cookies en dollars laat zien hoe de Nederlandse erfenis tot ver buiten New York reikt en zelfs

[Household purchase of sodas and cookies reduces the effect of an intervention to promote the consumption of fruits and vegetables].

Science.gov (United States)

Gomes, Fabio da Silva; Silva, Gulnar Azevedo E; Castro, Inês Rugani Ribeiro de

2017-04-03

This study examines the influence of increasing household availability of sodas and cookies on the effects of an intervention to promote the consumption of fruits and vegetables. The study analyzed data from 70 families living in low-income communities in the city of Rio de Janeiro, Brazil, selected in a stratified probabilistic sample, and who completed a 30-day food record before and after the intervention. The intervention contributed to a significant increase in the household availability of fruit and vegetables (+2.7 p.p.; 95%CI: 1.5; 4.0), contrary to the trend towards stagnation of such availability in the general population in Brazil. Meanwhile, the purchase of sodas and cookies, which was not the intervention's target, mirrored the upward trend in the consumption of these products (+5.8 p.p.; 95%CI: 3.3; 8.4). Families that increased their purchase of sodas and cookies showed lower increases, or even decreases, in the purchase of fruits and vegetables (p fruits and vegetables.

Effect of Lupine Flour on Baking Characteristics of Gluten Free Cookies

OpenAIRE

Sofyan Maghaydah; Selma Abdul-hussain; Radwan Ajo; Yousef Tawalbeh; Noor Elsahoryi

2013-01-01

Celiac Disease (CD) is an immune-mediated disease in genetically susceptible individuals caused by intolerance to gluten protein in some cereals, resulting in mucosal inflammation, which causes malabsorption. An effective treatment for CD is a gluten-free diet that excludes cereals containing gluten. One of the most desirable wheat products is the cookie, which is considered suitable for all ages due to its low manufacturing cost, convenience, long shelf life and good eating quality. Therefor...

Effects of returning NF concentrate on the MBR-NF process treating antibiotic production wastewater.

Science.gov (United States)

Li, Kun; Cheng, Yutao; Wang, Jianxing; Zhang, Junya; Liu, Jibao; Yu, Dawei; Li, Mingyue; Wei, Yuansong

2016-07-01

The optimization of the nanofiltration (NF) concentrate backflow ratio (R cb) and the influence of the NF concentrate on the performance of membrane bioreactor-nanofiltration (MBR-NF) process treating antibiotic production wastewater were investigated on a laboratory scale. The R cb was optimized at 60 % based on the removal rates of chemical oxygen demand (COD) and NH4 (+)-N by MBR. Data analyses indicated that salinity brought by NF concentrate is the major driver leading to the decrease of sludge activity, especially at a high R cb. EPS analysis showed that electric conductivity (EC), proteins in soluble microbial products (SMP), and SMP brought by NF concentrate are the dominant factors causing the severe membrane fouling in MBR. Furthermore, undegradable substances including fulvic acid-like and humic acid-like compounds accumulated in NF concentrate showed significant influence on fouling of NF. MBR could well degrade small MW compounds in NF concentrate, which confirmed the enhancement of organic removal efficiency by recycling the NF concentrate to MBR. The MBR-NF process showed a relatively stable performance at the R cb of 60 % (volume reduction factor (VRF) = 5), and the NF permeate could satisfy the water quality standard for fermentation process with a water recovery rate of 90.9 %.

Effects of awareness that food intake is being measured by a universal eating monitor on the consumption of a pasta lunch and a cookie snack in healthy female volunteers☆

Science.gov (United States)

Thomas, J.M.; Dourish, C.T.; Higgs, S.

2015-01-01

To date, there have been no studies that have explicitly examined the effect of awareness on the consumption of food from a Universal Eating Monitor (UEM – hidden balance interfaced to a computer which covertly records eating behaviour). We tested whether awareness of a UEM affected consumption of a pasta lunch and a cookie snack. 39 female participants were randomly assigned to either an aware or unaware condition. After being informed of the presence of the UEM (aware) or not being told about its presence (unaware), participants consumed ad-libitum a pasta lunch from the UEM followed by a cookie snack. Awareness of the UEM did not significantly affect the amount of pasta or cookies eaten. However, awareness significantly reduced the rate of cookie consumption. These results suggest that awareness of being monitored by the UEM has no effect on the consumption of a pasta meal, but does influence the consumption of a cookie snack in the absence of hunger. Hence, energy dense snack foods consumed after a meal may be more susceptible to awareness of monitoring than staple food items. PMID:26048004

Effects of whole-wheat flour and bordeaux grape pomace (Vitis labrusca L. on the sensory, physicochemical and functional properties of cookies

Directory of Open Access Journals (Sweden)

Ariadne Roberto KARNOPP

2015-12-01

Full Text Available Abstract Grape pomace, which is derived from the skin and seeds, is the residue from the production of grape juice and wine. It corresponds to up to 20% of the total volume and it contains a high level of dietary fibers and bioactive compounds. In the Brazilian market, there is no product containing grape pomace as a replacement for conventional wheat flour. Thus, this study aimed to assess the effects of whole-wheat flour and organic Bordeaux grape pomace (Vitis labrusca L. on the sensory, physicochemical and functional properties of cookies using response surface methodology (RSM. The regression models indicated that the addition of whole-wheat and organic grape pomace decreased (p 65% of explained data variability, except for brittleness. The sensory evaluation results revealed that no significant differences (p > 0.05 were observed for the cookie samples, implying that the addition of grape pomace and whole-wheat flour did not negatively affect the preference of cookies.

Influence of the type of fat and air humidity on chosen properties of the lipid fraction in the process of baking shortbread pastries

Directory of Open Access Journals (Sweden)

Miśkiewicz, K.

2013-03-01

Full Text Available The results from his study reveal that the type of fat used during the baking of shortbreads had a noticeable influence on the properties of lipid fractions as well as the correlation among these properties (acid value, peroxide value, conjugated dienes and trienes contents. For low-trans fats, the correlation between acid value and peroxide value was inversely proportional; for transcontaining fats this correlation was directly proportional. An increase in air humidity during baking caused a decrease in the melting temperature of the fractions of fats used in the process, compared to fats from pastries baked in dry air. This may be indicative of a product with a high degree of unsaturation in the lipid fraction.

Los resultados de este estudio demuestran que el tipo de grasa utilizada en el horneado de mantecadas tienen una influencia evidente en las propiedades de la fracción lipídica y una correlación entre estas propiedades (acidez, peróxidos, dienos y trienos conjugados. Para grasas bajas en trans la correlación entre la acidez y el índice de peróxido es inversamente proporcional, para grasas conteniendo trans esta correlación fue directamente proporcional. Un aumento de la humedad del aire durante el horneado causa una disminución de la temperatura de fusión de las fracciones de grasas utilizadas en el proceso, en comparación con las grasas de repostería horneadas en aire seco. Esto puede indicar la presencia de productos con alto grado de insaturación en las fracciones lipídicas.

Effects of awareness that food intake is being measured by a universal eating monitor on the consumption of a pasta lunch and a cookie snack in healthy female volunteers.

Science.gov (United States)

Thomas, J M; Dourish, C T; Higgs, S

2015-09-01

To date, there have been no studies that have explicitly examined the effect of awareness on the consumption of food from a Universal Eating Monitor (UEM - hidden balance interfaced to a computer which covertly records eating behaviour). We tested whether awareness of a UEM affected consumption of a pasta lunch and a cookie snack. 39 female participants were randomly assigned to either an aware or unaware condition. After being informed of the presence of the UEM (aware) or not being told about its presence (unaware), participants consumed ad-libitum a pasta lunch from the UEM followed by a cookie snack. Awareness of the UEM did not significantly affect the amount of pasta or cookies eaten. However, awareness significantly reduced the rate of cookie consumption. These results suggest that awareness of being monitored by the UEM has no effect on the consumption of a pasta meal, but does influence the consumption of a cookie snack in the absence of hunger. Hence, energy dense snack foods consumed after a meal may be more susceptible to awareness of monitoring than staple food items. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Generation and quenching of NF(a) and NF(b) molecules

International Nuclear Information System (INIS)

Setser, D.W.; Cha, H.; Quinones, E.; Du, K.

1987-01-01

The Ar( 3 Po,2) + NF 2 and 2F + HN 3 reactions have been developed as sources of NF(b 1 Σ + ) and NF(a 1 Δ) molecules, respectively, in a flow reactor. The decay kinetics for these molecules in the presence of added reagent can be studied using standard flow reactor techniques. Room temperature quenching rate constants for both molecules are reported for several reagents and compared to results for the isoelectronic O 2 (a) and O 2 (b) molecules

OsNF-YC2 and OsNF-YC4 proteins inhibit flowering under long-day conditions in rice

KAUST Repository

Kim, SoonKap

2015-11-05

OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response through the modulation of three flowering-time genes ( Ehd1, Hd3a , and RFT1 ) in rice. Plant NUCLEAR FACTOR Y (NF-Y) transcription factors control numerous developmental processes by forming heterotrimeric complexes, but little is known about their roles in flowering in rice. In this study, it is shown that some subunits of OsNF-YB and OsNF-YC interact with each other, and among them, OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response of rice. Protein interaction studies showed that the physical interactions occurred between the three OsNF-YC proteins (OsNF-YC2, OsNF-YC4 and OsNF-YC6) and three OsNF-YB proteins (OsNF-YB8, OsNF-YB10 and OsNF-YB11). Repression and overexpression of the OsNF-YC2 and OsNF-YC4 genes revealed that they act as inhibitors of flowering only under long-day (LD) conditions. Overexpression of OsNF-YC6, however, promoted flowering only under LD conditions, suggesting it could function as a flowering promoter. These phenotypes correlated with the changes in the expression of three rice flowering-time genes [Early heading date 1 (Ehd1), Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1)]. The diurnal and tissue-specific expression patterns of the subsets of OsNF-YB and OsNF-YC genes were similar to those of CCT domain encoding genes such as OsCO3, Heading date 1 (Hd1) and Ghd7. We propose that OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response by interacting directly with OsNF-YB8, OsNF-YB10 or OsNF-YB11 proteins in rice.

Innovation on Street Food Products (Instant Porridge and Cookies Based on Fortified Patin Fish Protein Concentrate with Red Palm Oil and Encaptulated Oil Fish

Directory of Open Access Journals (Sweden)

Dewita

2016-02-01

Full Text Available This research aimed to establish innovation on street food (instant porridge and cookies from Patin Fish Protein Concentrate fortified by blending red palm oil and encaptulated patin fish’s oil. The Encaptulation was conducted by blending of red palm oil and patin fish’s oil using spray dryer. The blending was consisted of three combinations namely 50 : 50 (A1, 40 : 60 (A2 and 60 : 40 (A3 for ratio between red palm oil and patin fish’s oil. The best combination’s results was fortified into street food (instant porridge and cookies. The blending was tested by measure yield, fat and fatty acid profile. Moreover, organoleptics and proximate tests were carrie out for the best treatment of blending in instant porridge and cookies. The results show that encaptulated yield reached 55 % that rise from A1 treatment as the best treatment with fat content of 17.26%. Profile of unsaturated fatty acid especially fatty acid omega 9 from blending fish oil and palm oil was 59.29%. The number of fatty acid omega 9 was higher than saturated fatty acid which was 18.56%. Furthermore, based on organoleptic tests of instant porridge and cookies using under five year children respondents, it was proven that 93% of children was like the products. Proximateanalysis of instant porridge revealed that protein content was 11.04 %, water content was 5.03%, fat content was 1.92 % and ash was 0.64 %. However, proximate analysis showed that cookies owned protein of 9.11%, fat of 17.03% , water content was 3.93% and ash of 1.38%.

Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

KAUST Repository

Hwang, Yoon-Hyung; Kim, SoonKap; Lee, Keh Chien; Chung, Young Soo; Lee, Jeong Hwan; Kim, Jeong-Kook

2016-01-01

Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

KAUST Repository

Hwang, Yoon-Hyung

2016-01-11

Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are required in early embryogenesis.

Directory of Open Access Journals (Sweden)

Monica Fornari

Full Text Available Nuclear factor Y (NF-Y is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as gametogenesis, embryogenesis, seed development, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 genes control early embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos fail to undergo to the heart stage and develop into abnormal globular embryos with both proembryo and suspensor characterized by a disordered cell cluster with an irregular shape, suggesting defects in embryo development. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin response in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis of Arabidopsis thaliana.

Biochemical characterisation and dietary fibre analysis of sugar beet supplemented cookies

International Nuclear Information System (INIS)

Pasha, I.; Jahangir, M.F.; Akhter, S.; Manzoor, M.S.

2016-01-01

This study was planned to utilize sugar beet powder as a rich source of dietary fibre in cookies. Purposely, five treatments namely T1, T2, T3, T4 and T5 with 4%, 8%, 12%, 16% and 20% sugar beet powder addition in wheat flour were chosen to estimate fibre, antioxidant profiling and engineering properties of cookies. Results showed an increased content of all above mentioned parameters. With the increment in sugar beet powder addition in treatments, dietary fibre analysis have shown that total dietary fibre (TDF), insoluble dietary fibre (IDF) and soluble dietary fibre (SDF) have depicted increasing trend with maximum for T5 for all dietary fibre types. Significant results were obtained for in vitro antioxidant studies including total phenolic content (TPC) and DPPH that showed increasing trend with T1 0.6 mg GAE/g and maximum values for T5 with 2.0 mg GAE/g for TPC and for DPPH with T5 being maximum value of 1.7% and minimum for T1 with 1.3%. T5 treatment with 20% sugar beet gave best physicochemical results but disturbed sensory properties while T3 with 12% sugar beet powder showed good physicochemical and sensory characteristics. Therefore, T3 with 12% level is considered as the best source of dietary fibre in bakery products and can be considered as the prospective choice to address metabolic syndromes. (author)

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

International Nuclear Information System (INIS)

Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D. Wade; De Vries, George H.

2006-01-01

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells

Biscoitos tipo "cookie" e "snack" enriquecidos, respectivamente com caseína obtida por coagulação enzimática e caseinato de sódio Sweet and salted biscuits (snacks enriched, respectively, with enzyme coagulated casein and sodium caseinate

Directory of Open Access Journals (Sweden)

C.C.H. Krüger

2003-04-01

Full Text Available O objetivo do presente trabalho foi a formulação e a caracterização química, nutricional e sensorial de dois tipos de biscoito, tipo "cookie" e "snack", utilizando para o enriquecimento protéico a caseína obtida por coagulação enzimática para o "cookie" e caseinato de sódio para o "snack". O biscoito tipo "cookie" apresentou teores mais elevados de umidade, proteína e fibra total que o do tipo "snack", que foi mais rico em gordura e sal. Com relação aos minerais essenciais, o biscoito tipo "cookie" apresentou-se mais rico em minerais que o "snack", exceto pelo fósforo e pelo sódio com teores mais elevados no "snack". O perfil de aminoácidos essenciais foi mais adequado no tipo "cookie" que no "snack". Conseqüentemente, os índices de valor protéico, exceto a digestibilidade verdadeira, foram superiores para os biscoitos do tipo "cookie". A aceitabilidade dos dois tipos de biscoito foi testada em atletas dos dois sexos com relação aos atributos: aceitação global, cor da superfície, odor, sabor, crocância e dureza. A aceitação dos produtos foi de 98% para os "snacks" e 81% para os "cookies". Os "cookies" tiveram o mesmo nível de aceitação pelos homens e pelas mulheres, já os "snacks" foram mais bem aceitos pelos homens (52,7% dos homens gostaram muito, contra apenas 37,8% das mulheres. A análise microbiológica dos dois tipos de biscoito mostrou perfil microbiológico aceitável, com base na Portaria 451 da Secretaria de Vigilância Sanitária.The objective of the present work was the formulation and characterization, chemical, nutritional and sensorial, of two types of biscuits, cookie and snack, using rennet casein and sodium caseinate for cookies and snacks enrichment, respectively. The cookie type biscuit presented higher contents of moisture, protein, and total fiber than the snack type which was richer in fat and salt. As to essential minerals the cookies were richer than the snacks, except for sodium and

A sensory analysis of butter cookies: An application of generalized procrustes analysis

OpenAIRE

Juhl, Hans Jørn

1994-01-01

Executive Summary: 1. A sensory analysis is one of the first steps in product development in the food industry. A thorough analysis of the results from such an analysis may give important input to the development process. 2. A sensory analysis on butter cookies is conducted in order to evaluate if some butter may be replaced by vegetable fat without a significant change in the sensory profile. The conclusion is that the replacement is possible without a considerable change in the sensory prof...

Impact of the two different iron fortified cookies on treatment of anemia in preschool children in Brazil.

Science.gov (United States)

Landim, Liejy Agnes; Pessoa, Marcia Luiza Dos Santos Beserra; Brandão, Amanda de Castro Amorim Serpa; Morgano, Marcelo Antonio; Marcos Antônio de Mota Araújo, Marcos Antônio De Mota Araújo; Rocha, Maurisrael De Moura; Arêas, José Alfredo Gomes; Moreira-Araújo, Regilda Saraiva Dos Reis

2016-09-20

Nutritional intervention in pre-school children using cookies prepared with wheat flour enriched with iron and folic acid (CWFFeFA) and cookies prepared with cowpea (Vigna unguiculata (L.) Walp) flour fortified with iron and zinc and wheat flour enriched with iron and folic acid (CCFFeZn + WFFeFA). To assess the impact of the ingestion of CWFFeFA and CCFFeZn + WFFeFA by pre-school children, using the cowpea variety BRS-Xiquexique, to control iron-deficiency anaemia. Nutritional intervention was conducted in municipal day care centres selected at random (n = 262) involving pre-school children aged 2 to 5 years living in Teresina, state of Piauí, Brazil. To assess the socioeconomic data, BMI-for-age, haemoglobin levels before and after intervention, and dietary intake, the children were divided into group 1 (G1), which received CWFFeFA (30 g), and group 2 (G2), which received CCFFeZn + WFFeFA (30 g). Food acceptance was evaluated daily. The prevalence of anaemia in G1 and G2 before the nutritional intervention was 12.2% (n = 18) and 11.5% (n = 30), respectively. After intervention, the prevalence decreased to 1.4% in G1 (n = 2) and to 4.2% in G2 (n = 11). Food acceptance by pre-school children in G1 and G2 was 97.4% and 94.3%, respectively. The use of both types of cookie formulations decreased the prevalence of anaemia among pre-school children, and CCFFeZn + WFFeFA yielded the greatest decrease.

Evaluation of two local cowpea species for nutrient, antinutrient, and phytochemical compositions and organoleptic attributes of their wheat-based cookies

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Rufina N. B. Ayogu

2016-01-01

Full Text Available Background: Childhood and adolescent malnutrition is a function of inadequate intake. Cookies are favourite snacks of children and adolescents. Objective: This work determined the nutrient, antinutrient, and phytochemical compositions of two local cowpea (oraludi and apama flours and evaluated the organoleptic properties of their wheat-based cookies. Design: The two local cowpea species were processed into flours separately and blended with wheat on a 56-g protein basis. Chemical compositions of the processed cowpea flours were analysed using standard methods. Organoleptic attributes were evaluated with a nine-point Hedonic scale. Statistical analysis, which involved mean and standard deviations, were computed by analysis of variance, and Duncan's new multiple range tests were used to separate and compare group means of sensory evaluation data, with significance accepted at P<0.05. Results: The results revealed that oraludi had superior percentage values compared to apama in protein (26.22 and 20.88, fat (7.98 and 6.65, and ash (3.81 and 3.13, while apama proved superior in moisture (9.76 and 7.82, crude fibre (5.49 and 4.91, and carbohydrate (54.09 and 49.26. The values were higher for oraludi than apama in iron (8.62 and 6.49 mg, zinc (1.61 and 0.95 mg, and beta-carotene (223.24 and 190.63 mg but lower in sodium (34.79 and 56.72 mg, potassium (25.73 and 30.65 mg, phosphorus (13.35 and 18.26 mg, thiamine (5.33 and 9.41 mg, vitamin C (16.63 and 21.09 mg, and vitamin E (0.51 and 0.67 mg. Apama had 0.06 mg phytate, 0.09 mg oxalate, 15.22 mg tannins, 3.59 mg flavonoids, and 0.19 mg saponin. Oraludi had 0.03 mg phytate, 0.32 mg oxalate, 15.94 mg tannins, 3.14 mg flavonoid, and 0.13 mg saponin. Mean scores of general acceptability for wheat:apama (80:20 and wheat:oraludi:apama (60:20:20 cookies (7.71 and 7.41 were superior (P<0.05 to others. Conclusions: Oraludi and apama proved nutrient dense. Their use improved the acceptability of some of the

Eating Christmas Cookies, Whole-wheat Bread and Frozen Chicken in the Kindergarten: Doing Pedagogy by Other Means

NARCIS (Netherlands)

Kontopodis, M.

2013-01-01

The study presented here explores eating as a pedagogical practice by paying attention to arrangements of things such as Christmas cookies, whole-wheat and white bread, frozen chicken, plates, chairs, tables, and freezers. Through a series of ethnographic research examples from German and Brazilian

Using chemometric techniques to characterize gluten-free cookies containing the whole flour of a new quinoa cultivar

International Nuclear Information System (INIS)

Pagamunici, Lilian M.; Gohara, Aline K.; Souza, Aloisio H.P.; Batiston, Weliton P.; Gomes, Sandra T.M.; Visentainer, Jesui V.; Matsushita, Makoto

2014-01-01

Celiac disease is defined as intolerance to the gluten proteins present in certain cereals used to prepare foodstuffs. We developed and performed physico-chemical, sensory, and nutritional assessments of three formulations of gluten-free cookies containing Linum usitatissimum L. and different levels of whole Chenopodium quinoa BRS Piabiru flour. No gluten was detected in the prepared cookie formulations. The crude protein and total lipid contents ranged from 85.58 to 97.55 and 121.69 to 166.19 g per kg of sample, respectively. The polyunsaturated/saturated and n-6:n-3 fatty acid ratios ranged from 0.85:1 to 0.92:1 and 3.08:1 to 4.38:1, respectively. Formulation C had the best alpha-linolenic acid content, lipid fraction nutritional indices and mineral content per portion, with excellent sensory characteristics. Multivariate analysis highlighted the effect of the concentration of quinoa on the nutritional and sensory qualities of the product. (author)

Using chemometric techniques to characterize gluten-free cookies containing the whole flour of a new quinoa cultivar

Energy Technology Data Exchange (ETDEWEB)

Pagamunici, Lilian M.; Gohara, Aline K.; Souza, Aloisio H.P. [Universidade Estadual de Maringa (UEM), PR (Brazil). Centro de Ciencias Agrarias; Bittencourt, Paulo R.S.; Torquato, Alex S. [Universidade Tecnologica Federal do Parana (UTFPR), Medianeira, PR (Brazil); Batiston, Weliton P.; Gomes, Sandra T.M.; Visentainer, Jesui V.; Matsushita, Makoto, E-mail: mmakoto@uem.br [Universidade Estadual de Maringa (UEM), PR (Brazil). Dept. de Quimica; Souza, Nilson E. [Universidade Tecnologica Federal do Parana (UTFPR), Londrina, PR (Brazil)

2014-02-15

Celiac disease is defined as intolerance to the gluten proteins present in certain cereals used to prepare foodstuffs. We developed and performed physico-chemical, sensory, and nutritional assessments of three formulations of gluten-free cookies containing Linum usitatissimum L. and different levels of whole Chenopodium quinoa BRS Piabiru flour. No gluten was detected in the prepared cookie formulations. The crude protein and total lipid contents ranged from 85.58 to 97.55 and 121.69 to 166.19 g per kg of sample, respectively. The polyunsaturated/saturated and n-6:n-3 fatty acid ratios ranged from 0.85:1 to 0.92:1 and 3.08:1 to 4.38:1, respectively. Formulation C had the best alpha-linolenic acid content, lipid fraction nutritional indices and mineral content per portion, with excellent sensory characteristics. Multivariate analysis highlighted the effect of the concentration of quinoa on the nutritional and sensory qualities of the product. (author)

Quality characteristics of gluten-free cookies made of buckwheat, corn, and rice flour with/without transglutaminase.

Science.gov (United States)

Altındağ, Gülçin; Certel, Muharrem; Erem, Fundagül; İlknur Konak, Ülgen

2015-04-01

Buckwheat is one of the most valuable pseudo-cereals in terms of its nutritional composition, and it is suitable for celiac patients because of its gluten-free characteristic. However, gluten is the main structure-forming protein responsible for the development of structure in baked products. Therefore, it is a challenge to produce high-quality gluten-free products. Transglutaminase addition is a relatively common application used in the production of gluten-free baked goods. The objective of this study was to investigate the combination of buckwheat flour with rice and corn flour at different levels in gluten-free cookie formulations and the impact of transglutaminase on the quality of cookies. Quality parameters evaluated were proximal chemical composition, spread ratio, color, and textural parameters (hardness and fracturability). Spread ratio, protein, crude fiber, ash content, and also b* and hardness values were significantly (p flour combinations. Further, addition of transglutaminase resulted in increased moisture content, spread ratio, and fracturability but decreased hardness values. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Elaboração e caracterização de cookies sem glúten enriquecidos com farinha de coco: uma alternativa para celíacos

Directory of Open Access Journals (Sweden)

Ana Maria Queiroz

2017-05-01

Full Text Available Resumo Os celíacos encontram dificuldades na adoção de uma dieta totalmente isenta de glúten e com qualidade nutricional. Para tanto, objetivou-se desenvolver e avaliar cookies sem glúten enriquecidos com farinha de coco. A farinha de coco com elevado teor de cinzas, proteínas e lipídios pode ser utilizada para enriquecer produtos alimentícios. Foram elaborados cookies com base na composição de uma mistura da Federação Nacional das Associações de Celíacos do Brasil - Fenacelbra (“mix de farinha preparada II” para cookies sem glúten: Padrão FP (formulação semelhante à composição do “mix de farinha preparada II” da Fenacelbra, F1 (modificação de FP com substituição da fécula de batata por 10% de farinha de coco, F2 (modificação de FP com adição de 5% de farinha de coco, F3 (modificação de FP com substituição do polvilho doce por 5% de farinha de coco. Os cookies foram avaliados quanto às características físicas (peso pós-cocção, diâmetro e espessura pós-cocção, fator de expansão, rendimento, Aw, dureza e cor – L*a*b*, físico-químicas (umidade, cinzas, proteínas, lipídios, carboidratos e valor calórico, aceitabilidade quanto aos atributos sensoriais (aceitação global, aparência, cor, aroma, sabor e textura e atitude de compra. A adição de farinha de coco às formulações melhorou as propriedades nutricionais dos cookies sem glúten, aumentando o teor de lipídios e proteínas, e reduzindo o teor de carboidratos. Os cookies desenvolvidos apresentaram boa aceitação sensorial e intenção de compra satisfatória., A adição de 10% de farinha de coco em substituição da fécula de batata na formulação F1 não alterou as características sensoriais do produto, porém proporcionou propriedades físicas e físico-químicas superiores. Dessa forma, cookies sem glúten enriquecidos com farinha de coco constituem uma alternativa viável de alimentos destinados para pessoas portadoras de

Avaliação física, físico-química e sensorial de cookies enriquecidos com farinha de açaí

Directory of Open Access Journals (Sweden)

A. V. S. Azevedo

2015-12-01

Full Text Available Os biscoitos apresentam grande consumo, longa vida de prateleira e boa aceitação, e nos dias atuais têm sido formulados com a intenção de torná-los mais nutritivos para a melhoria da qualidade da dieta dos consumidores. O açaí apresenta alto teor de antocianinas e alto valor energético, sendo rico em fibras, vitamina E, proteínas, minerais e ácidos graxos essenciais como Ômega-6 e Ômega-9. O objetivo deste estudo foi elaborar biscoitos tipo cookies utilizando diferentes concentrações de farinha de açaí, avaliar suas características físicas, físico-químicas e a sua aceitação sensorial. A partir de uma formulação padrão, foram adicionados 100 g (FA, 80 g (FB e 60 g (FC de farinha de açaí totalizando três amostras. Avaliaram-se os biscoitos quando à umidade, cinzas, pH, acidez, cor e textura. Os testes sensoriais foram realizados com 50 julgadores não treinados, utilizando uma escala hedônica para avaliação dos atributos bem como o teste de intenção de compra. Não houve diferença significativa entre as diferentes formulações de cookies quando ao conteúdo de cinzas e para o parâmetro de textura fraturabilidade. A formulação A apresentou um valor muito elevado no parâmetro dureza (28,81 N e uma coloração muito escura (L* 43,97. Os resultados da análise sensorial demonstraram satisfatória a aceitação do cookies com farinha de açaí, apresentado escores acima de 6,0 em relação a todos os atributos. A formulação B apresentou melhor escore para a intenção de compra e foi caracterizado pelos parâmetros sabor e aroma na análise de componentes principais, apresentando os melhores resultados para os parâmetros estudados.Evaluation of physical, physico-chemical and sensory of cookies with added acai flourAbstract: The cookies have great consumption, long shelf life and good acceptance, and nowadays have been formulated with the intention of making them more nutritious for improving the quality of

[NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].

Science.gov (United States)

Jimi, Eijiro; Fukushima, Hidefumi

2016-02-01

The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.

A sensory analysis of butter cookies: An application of generalized procrustes analysis

DEFF Research Database (Denmark)

Juhl, Hans Jørn

1994-01-01

Executive Summary: 1. A sensory analysis is one of the first steps in product development in the food industry. A thorough analysis of the results from such an analysis may give important input to the development process. 2. A sensory analysis on butter cookies is conducted in order to evaluate...... if some butter may be replaced by vegetable fat without a significant change in the sensory profile. The conclusion is that the replacement is possible without a considerable change in the sensory profile. 3. Generalized Procrustes Analysis is used to analyze the results. It is a relatively new technique...

A new species of wedgefish Rhynchobatus cooki (Rhinopristiformes, Rhinidae) from the Indo-West Pacific.

Science.gov (United States)

Last, Peter R; Kyne, Peter M; Compagno, Leonard J V

2016-07-20

A new dwarf wedgefish, Rhynchobatus cooki sp. nov. is described from a single female from a Jakarta fish market (Indonesia) and 11 specimens collected at Jurong fish market (Singapore). First collected in 1934, the broader ichthyological community have been aware of this distinctive but little known ray since the late 1990's. Rhynchobatus cooki is the smallest of the wedgefishes (to 81 cm TL) and has the lowest vertebral count (fewer than 107 centra). It is also distinguishable from its congeners based on its long, hastate snout, very strongly undulate anterior pectoral-fin margin, coloration and aspects of its squamation. The dorsal coloration is mainly dark and distinctively marked with white blotches, spots and streaks, and has a dark cruciate marking on the interorbit and a prominent white border around the body margin. Unlike most other wedgefish species, the snout tip lacks dark blotches and there is no black pectoral-fin marking. It shares well-developed rostral spines with a much larger Atlantic species (Rhynchobatus luebberti), but these spines are confined to the snout tip (rather than being more numerous and extending in paired rows along the rostral ridges nearly to the eyes). No additional specimens have been observed since 1996, despite an increased recent effort to survey the chondrichthyan fauna of South-East Asia and collect biological data for species, raising concerns over its conservation status.

The C-terminal domains of NF-H and NF-M subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament network.

Directory of Open Access Journals (Sweden)

Mala V Rao

Full Text Available Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M(tailΔ] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M(tailΔ mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M(tailΔ axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.

A Targeted LC-MS/MS Method for the Simultaneous Detection and Quantitation of Egg, Milk, and Peanut Allergens in Sugar Cookies.

Science.gov (United States)

Boo, Chelsea C; Parker, Christine H; Jackson, Lauren S

2018-01-01

Food allergy is a growing public health concern, with many individuals reporting allergies to multiple food sources. Compliance with food labeling regulations and prevention of inadvertent cross-contact in manufacturing requires the use of reliable methods for the detection and quantitation of allergens in processed foods. In this work, a novel liquid chromatography-tandem mass spectrometry multiple-reaction monitoring method for multiallergen detection and quantitation of egg, milk, and peanut was developed and evaluated in an allergen-incurred baked sugar cookie matrix. A systematic evaluation of method parameters, including sample extraction, concentration, and digestion, were optimized for candidate allergen peptide markers. The optimized method enabled the reliable detection and quantitation of egg, milk, and peanut allergens in sugar cookies, with allergen concentrations as low as 5 ppm allergen-incurred ingredient.

Mastication and swallowing in patients with postirradiation xerostomia

International Nuclear Information System (INIS)

Hamlet, Sandra; Faull, Jennifer; Klein, Barbara; Aref, Amr; Fontanesi, James; Stachler, Robert; Shamsa, Falah; Jones, Lewis; Simpson, Mark

1997-01-01

Purpose: Very little objective data has been reported on mastication and swallowing in xerostomic patients, which would substantiate presumed causal relationships between xerostomia and patient complaints. The purpose was to elucidate which components of mastication and swallowing were abnormal, and most directly related to xerostomia, and which appeared unaffected. Methods and Materials: A retrospective analysis of timing events in mastication and swallowing was done using videofluoroscopic data for 15 cancer patients with xerostomia, and 20 normal controls. Scintigraphy was also used to determine oropharyngeal residue after a water swallow. Cancer treatment modalities included radiation therapy or chemoradiation therapy. Results: For barium liquid and paste substances, timing measures were equivalent for controls and patients. Xerostomic patients took 46% longer to masticate a shortbread cookie, and timing for the initiation of swallowing was shorter, but duration of swallowing appeared unaffected. Oral and pharyngeal residues following the swallow were greater in the patient group. Conclusions: Xerostomia primarily affected mastication and oral manipulation of a dry, absorbent food material. Increased oral and pharyngeal residues after a water swallow are ambiguously related to xerostomia. The initiation and duration of the pharyngeal swallow was not abnormal

Emprego de fubá de melhor qualidade protéica em farinhas mistas para produção de biscoito Use of quality-protein maize in flour blends and in the production of cookies

Directory of Open Access Journals (Sweden)

Fátima F. P. Guilherme

2005-03-01

Full Text Available Farinhas mistas (FM à base de farinha de trigo com substituição parcial por isolado protéico de soja, soro de leite em pó e três tipos de fubá (mimoso ou de cultivares BR451 e BR2121 foram preparadas para melhorar a qualidade protéica da farinha de trigo. As características sensoriais e químicas dos biscoitos foram avaliadas, e o valor protéico em potencial foi calculado. Os resultados foram comparados com os da farinha de trigo ou seu biscoito (controles. Os teores em macronutrientes nas FM e nos biscoitos foram superiores aos dos respectivos controles, com exceção de carboidratos. Apenas na aparência o biscoito com FM BR2121 foi estatisticamente inferior à daquele com FM mimoso, sendo semelhantes ao controle e aos outros biscoitos na textura e no sabor. O biscoito com FM mimoso teve a maior aceitação. O valor calórico médio dos biscoitos foi de 436kcal. A qualidade protéica dos biscoitos com as FM - lisina e treonina como aminoácidos limitantes e C-PER em torno de 2 - foi superior a do controle. O custo (preço/kg dos biscoitos assados com as FM foi superior ao do biscoito controle, devido ao custo da FM ter sido cerca do dobro da farinha de trigo pura e de se necessitar maiores quantidades de ingredientes na formulação.Flour blends (FB based on wheat flour with partial substitution for isolated soy protein, powdered whey and three corn flour types (common or cultivar BR451 and BR2121 were prepared to improve the protein quality of wheat flour. The sensory and chemical characteristics of the cookies were evaluated and the potential proteic value was calculated. The results were compared with the wheat flour or its cookie (controls. Macronutrients levels in FB and cookies were superior than those in the respective controls, except for carbohydrates. Only in the appearance the cookie made with FB BR2121 was statistically inferior to the one with common corn FB, being similar to the control and other cookies in texture and

The Regulation of NF-κB Subunits by Phosphorylation

Directory of Open Access Journals (Sweden)

Frank Christian

2016-03-01

Full Text Available The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.

Quality and Antioxidant Activity of Buckwheat-Based Cookies Designed for a Raw Food Vegan Diet as Affected by Moderate Drying Temperature.

Science.gov (United States)

Brožková, Iveta; Dvořáková, Veronika; Michálková, Kateřina; Červenka, Libor; Velichová, Helena

2016-12-01

Buckwheat cookies with various ingredients for raw food vegan diet are usually prepared by soaking them in water at ambient temperature followed by drying at moderate temperature. The aim of this study was to examine the temperature effect on the microbiological quality, antioxidant properties and oxidative stability of lipids of final dried samples. The mixture of ingredients was soaked for 20 h in distilled water, and then cookies were formed and dried in air-forced oven at constant temperature in the range from 40 to 60 °C. Total viable counts, fungi, yeasts, coliform and aerobic spore-forming bacteria counts were evaluated in dried samples and were found to decrease during drying at 50 and 60 °C. Antioxidant activity was determined by DPPH and ABTS assays, and the former showed the highest value at 40 °C. Superoxide dismutase activity was also higher at 40 °C in comparison with that at 60 °C. The percentage of lipid peroxidation inhibition increased with the increase in drying temperature until 4th day of incubation. While peroxide value was significantly higher in samples dried at 40 °C, TBARS values did not show significant changes during the drying process. The results of this study suggest that drying buckwheat-based cookies at 40 °C retained their good antioxidant properties but represent a potentially serious microbial hazard.

Effects of Sodium Chloride, Potassium Chloride and Calcium Chloride on the Formation of α-Dicarbonyl Compounds, Furfurals and Development of Browning in Cookies during Baking.

Science.gov (United States)

Kocadağlı, Tolgahan; Gökmen, Vural

2016-10-02

Effect of NaCl, KCl, CaCl2, NaHCO3, and NH4HCO3 on the formation of glucosone, 1-deoxyglucosone, 3-deoxyglucosone, glyoxal, methylglyoxal, diacetyl, 5-hydroxymethyl-2-furfural, 2-furfural and browning were investigated in cookies. Presence of 1.5% NaCl, 1% KCl, and 1% CaCl2 on flour basis had no effect on α-dicarbonyl compounds, except 1-deoxyglucosone increased in the presence of KCl and CaCl2. The increase in 5-hydroxymethyl-2-furfural formation in the presence of NaCl, KCl, and CaCl2 did not relate to 3-deoxyglucosone formation and pH changes. NaCl, KCl, and CaCl2 increased browning in cookies. Model reaction systems indicated that NaCl, KCl, and CaCl2 enhance browning by increasing furfurals in caramelization. NaCl, KCl, and CaCl2 decreased browning intensity in heated glucose-glycine system. Usage of CaCl2 in cookies may considerably increase furfurals but not α-dicarbonyl compounds. Sodium reduction can be obtained by replacement with potassium without sacrificing the desired consequences of caramelization in sugar rich bakeries.

The garlic NF-YC gene, AsNF-YC8, positively regulates non-ionic hyperosmotic stress tolerance in tobacco.

Science.gov (United States)

Sun, Xiudong; Lian, Haifeng; Liu, Xingchen; Zhou, Shumei; Liu, Shiqi

2017-05-01

To investigate the relationship between nuclear factor Y (NF-Y) and stress tolerance in garlic, we cloned a NF-Y family gene AsNF-YC8 from garlic, which was largely upregulated at dehydrate stage. Expression pattern analyses in garlic revealed that AsNF-YC8 is induced through abscisic acid (ABA) and abiotic stresses, such as NaCl and PEG. Compared with wild-type plants, the overexpressing-AsNF-YC8 transgenic tobacco plants showed higher seed germination rates, longer root length and better plant growth under salt and drought stresses. Under drought stress, the transgenic plants maintained higher relative water content (RWC), net photosynthesis, lower levels of malondialdehyde (MDA), and less ion leakage (IL) than wild-type control plants. These results indicate the high tolerance of the transgenic plants to drought stress compared to the WT. The transgenic tobacco lines accumulated less reactive oxygen species (ROS) and exhibited higher antioxidative enzyme activities compared with wild-type (WT) plants under drought stress, which suggested that the overexpression of AsNF-YC8 improves the antioxidant defense system by regulating the activities of these antioxidant enzymes, which in turn protect transgenic lines against drought stress. These results suggest that AsNF-YC8 plays an important role in tolerance to drought and salt stresses.

NF1 Neuronal Genotype Phenotype Relationships

Science.gov (United States)

2017-06-01

interesting results from the Drosophila functional assays, at present we have decided to focus our attention on selected NF1 patient missense mutations...complexity of NF1 disease phenotypes in different tissues, age and sex dependency of symptoms, impact of environmental factors and genetic heterogeneity...suggesting the role of modifier genes [12]. This work aims to shed light on this issue by studying the functional consequences of selected NF1

Blocking NF-κB: an inflammatory issue.

Science.gov (United States)

Rahman, Arshad; Fazal, Fabeha

2011-11-01

The nuclear factor (NF)-κB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF-κB for treatment of these diseases. However, recent studies showing that NF-κB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-κB. This article reviews the regulation of NF-κB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-κB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases.

Dissociation of NF3 in shock waves

International Nuclear Information System (INIS)

Breshears, W.D.; Bird, P.F.

1978-01-01

The thermal dissociation rate of NF 3 in mixtures of 5% and 10%NF 3 in Ar has been measured behind incident shock waves over the temperature range 1330-2000 K. Dissociation rates were determined from postshock density gradients measured by laser beam deflection. The second order rate coefficient determined for NF 3 -Ar collisions is k/sub d/=2.31 x 10 15 exp(-20500/T) cm 3 mole sec

Flour mill stream blending affects sugar snap cookie and Japanese sponge cake quality and oxidative cross-linking potential of soft white wheat.

Science.gov (United States)

The purpose of this research was to study the functional differences between straight grade (75% extraction rate) and patent (60% extraction rate) flour blends from 28 genetically pure soft white and club wheat grain lots, as evidenced by variation in sugar snap cookie and Japanese sponge cake quali...

Identification and characterization of NF-YB family genes in tung tree.

Science.gov (United States)

Yang, Susu; Wang, Yangdong; Yin, Hengfu; Guo, Haobo; Gao, Ming; Zhu, Huiping; Chen, Yicun

2015-12-01

The NF-YB transcription factor gene family encodes a subunit of the CCAAT box-binding factor (CBF), a highly conserved trimeric activator that strongly binds to the CCAAT box promoter element. Studies on model plants have shown that NF-YB proteins participate in important developmental and physiological processes, but little is known about NF-YB proteins in trees. Here, we identified seven NF-YB transcription factor-encoding genes in Vernicia fordii, an important oilseed tree in China. A phylogenetic analysis separated the genes into two groups; non-LEC1 type (VfNF-YB1, 5, 7, 9, 11, 13) and LEC1-type (VfNF-YB 14). A gene structure analysis showed that VfNF-YB 5 has three introns and the other genes have no introns. The seven VfNF-YB sequences contain highly conserved domains, a disordered region at the N terminus, and two long helix structures at the C terminus. Phylogenetic analyses showed that VfNF-YB family genes are highly homologous to GmNF-YB genes, and many of them are closely related to functionally characterized NF-YBs. In expression analyses of various tissues (root, stem, leaf, and kernel) and the root during pathogen infection, VfNF-YB1, 5, and 11 were dominantly expressed in kernels, and VfNF-YB7 and 9 were expressed only in the root. Different VfNF-YB family genes showed different responses to pathogen infection, suggesting that they play different roles in the pathogen response. Together, these findings represent the first extensive evaluation of the NF-YB family in tung tree and provide a foundation for dissecting the functions of VfNF-YB genes in seed development, stress adaption, fatty acid synthesis, and pathogen response.

NF-kappaB in Lung Tumorigenesis

International Nuclear Information System (INIS)

Cai, Zhenjian; Tchou-Wong, Kam-Meng; Rom, William N.

2011-01-01

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis

NF-kappaB in Lung Tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-12-14

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

NF-kappaB: Two Sides of the Same Coin.

Science.gov (United States)

Pires, Bruno R B; Silva, Rafael C M C; Ferreira, Gerson M; Abdelhay, Eliana

2018-01-09

Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies. In addition to the direct effects of NF-κB in cancer cells, it might also impact immune cells that can both promote or prevent tumor development. Currently, with the rise of cancer immunotherapy, the link among immune cells, inflammation, and cancer is a major focus, and NF-κB could be an important regulator for the success of these therapies. This review discusses the contrasting roles of NF-κB as a regulator of pro- and antitumor processes and its potential as a therapeutic target.

Phorbol-ester-induced activation of the NF-κB transcription factor involves dissociation of an apparently cytoplasmic NF-κB/inhibitor complex

International Nuclear Information System (INIS)

Baeuerle, P.A.; Lenardo, M.; Pierce, J.W.; Baltimore, D.

1988-01-01

There is increasing evidence that inducible transcription of genes is mediated through the induction of the activity of trans-acting protein factors. The NF-κB transcription factor provides a model system to study the posttranslational activation of a phorbol-ester-inducible transcription factor. The finding that NF-κB activity is undectable in subcellular fractions from unstimulated cells suggests that NF-κB exists as an inactive precursor. The authors showed that NF-κB is detectable in two different forms. After selective removal of endogenous NF-κB, they demonstrate the existence of a protein inhibitor in cytosolic fractions of unstimulated cells that is able in vitro to convert NF-κB into an inactive desoxycholate-dependent form. The data are consistent with a molecular mechanism of inducible gene expression by which an apparently cytoplasmic transcription factor-inhibitor complex is dissociated by the action of TPA-activated protein kinase C

A sensory evaluation of irradiated cookies made from flaxseed meal

International Nuclear Information System (INIS)

Rodrigues, Flávio T.; Fanaro, Gustavo B.; Duarte, Renato C.; Koike, Amanda C.; Villavicencio, Anna Lucia C.H.

2012-01-01

The growing consumer demand for food with sensory quality and nutritional has called for research to develop new products with consumer acceptance as cookies made from flaxseed meal, that can be inserted in diet of celiacs. Celiac disease characterized by an inappropriate immune response to dietary proteins found in wheat, rye and barley (gluten and gliadin). It can affect anyone at any age and is more common in women. The celiac disease does not have cure and the only scientifically proven treatment is a gluten free diet. Irradiation as a decontamination method used for a many variety of foodstuffs, being very feasible, useful method to increase the shelf life, effective and environmental friendly without any sensory properties significant change. Sensory analyses were used to assess gluten-free bakery foods subjected to ionizing radiation sensory attributes. - Highlights: ► Celiac disease is an inappropriate immune response to dietary proteins. ► Irradiation is an useful method to increase the food shelf life. ► Sensory analysis is applied in the improvement of the quality of foods.

EFEITO DA ADIÇÃO DE AMARANTO NA COMPOSIÇÃO E NA ACEITABILIDADE DO BISCOITO TIPO COOKIE E DO PÃO DE FORMA

Directory of Open Access Journals (Sweden)

V. D. CAPRILES

2009-01-01

Full Text Available

O amaranto é um pseudocereal de origem andina, de elevado valor nutritivo, pouco difundido no Brasil. Seu uso em produtos convencionais é desejável para o aumento da oferta de nutrientes de importância para a população. O presente trabalho avaliou o impacto da substituição parcial da farinha de trigo pelas farinhas de amaranto integral (FAI e desengordurada (FAD sobre o valor nutritivo e a aceitabilidade sensorial do biscoito tipo cookie e do pão de forma. A substituição de 30% nos cookies e 26% nos pães resultou em aumento do valor nutricional, gerando produtos fonte de fibra alimentar e com expressivo aumento dos teores de cálcio e ferro. Os novos produtos apresentaram elevada aceitabilidade sensorial e não foram observadas diferenças significativas entre a aceitabilidade dos cookies ou dos pães obtidos com FAI e FAD. Concluise que a incorporação das farinhas de amaranto na formulação de pães de forma e biscoitos tipo cookie é interessante comercialmente e promove o incremento dos teores de fibra, cálcio e ferro gerando produtos de elevada aceitabilidade sensorial. Estes resultados mostram a possibilidade do uso desta matéria prima na elaboração de produtos convencionais contribuindo para a difusão do amaranto no país.

Temperature-dependent interaction potential between NF3 molecules and thermophysical properties of gaseous NF3

International Nuclear Information System (INIS)

Damyanova, M; Balabanova, E; Hohm, U

2014-01-01

A temperature-dependent effective intermolecular interaction potential is applied to describe the interaction between two nitrogen fluoride (NF 3 ) molecules in gas phase. To this end, a spherically-symmetric (n-6) Lennard-Jones temperature-dependent potential (LJTDP) is used. The (n-6) LJTDP takes into account the influence of vibrational excitation of the molecules on the potential parameters, namely, the equilibrium distance r m and the potential well depth ε. The potential parameters at T = 0 K were obtained from the very small amount of existing thermophysical equilibrium and transport properties of low-density NF 3 gas. Fitting formulae are tabulated for a fast and reliable prediction of the thermophysical properties and potential parameters in the temperature range between 200 K and 1200 K. A comparison is also presented between our estimates for some thermophysical properties of the NF 3 gas with the available experimental and calculated data.

Packaging Design and Marketing Strategy of Cookie%饼干包装设计与营销策略

Institute of Scientific and Technical Information of China (English)

潘依华

2015-01-01

"The best selling product is the impression of the goods". Packaging is not only the outside protec-tion of the product, but also is a kind of marketing strategy. The quality of packaging design always impresses the effect of the advertising of the goods, and become one of the important factor in developing market. The packaging design strategy of cookie is a very logical creation progress in selling. So the research of packaging design and mar-keting strategy is meaningful to promoting market competitiveness of the cookie product.%"商品畅销的诀窍在于商品的印象."包装既是对产品的外在保护,更是一种营销策略,包装设计的好坏往往会影响到该产品的广告宣传效应,成为产品开拓市场的重要影响因素之一.饼干产品的包装设计策略是一个非常逻辑化的促销创意过程.因此,研究包装的设计及营销,对于提升饼干产品的市场竞争力具有重要的意义.

Processing of commercial peanut cake into food-grade meal and its utilization in preparation of cookies.

Science.gov (United States)

Tate, P V; Chavan, J K; Patil, P B; Kadam, S S

1990-04-01

The commercial cake produced during expeller pressing of peanuts was extracted with n-hexane, and 80% ethanol followed by sieving through 80 mesh, to remove residual oil, pigments, bitter taste and fibrous material. The processed meal exhibited comparable composition with defatted peanut flour prepared in the laboratory by solvent extraction of full-fat peanut meal. However, the processed cake meal exhibited low methionine content and in vitro protein digestibility as compared with defatted peanut flour. The processed cake meal can be blended with wheat flour to the extent of 10% (w/w) to prepare acceptable cookies with improved protein and mineral contents.

Genetic Factors that Affect Tumorigenesis in NF1

National Research Council Canada - National Science Library

Stephens, Karen

2003-01-01

...) that flank the NF1 gene. We identified recombination hotspots where 69% of NF1 microdeletions occur and developed robust and sensitive assays to detect microdeletions in a patient blood sample...

Genetic Factors that Affect Tumorigenesis in NF1

National Research Council Canada - National Science Library

Stephens, Karen G

2004-01-01

...) that flank the NF1 gene. We identified recombination hotspots where 69% of NF1 microdeletions occur and developed robust and sensitive assays to detect microdeletions in a patient blood sample...

Innovation on Street Food Products (Instant Porridge and Cookies Based on Fortified Patin Fish Protein Concentrate with Red Palm Oil and Encaptulated Oil Fish

Directory of Open Access Journals (Sweden)

Dewita Dewita

2015-02-01

Full Text Available This research aimed to establish innovation on street food (instant porridge and cookiesfrom Patin Fish Protein Concentrate fortified by blending red palm oil and encaptulated patinfish’s oil. The Encaptulation was conducted by blending of red palm oil and patin fish’s oil usingspray dryer. The blending was consisted of three combinations namely 50 : 50 (A1, 40 : 60 (A2and 60 : 40 (A3 for ratio between red palm oil and patin fish’s oil. The best combination’s resultswas fortified into street food (instant porridge and cookies. The blending was tested by measureyield, fat and fatty acid profile. Moreover, organoleptics and proximate tests were carrie out for thebest treatment of blending in instant porridge and cookies. The results show that encaptulatedyield reached 55 % that rise from A1 treatment as the best treatment with fat content of 17.26%.Profile of unsaturated fatty acid especially fatty acid omega 9 from blending fish oil and palm oilwas 59.29%. The number of fatty acid omega 9 was higher than saturated fatty acid which was18.56%. Furthermore, based on organoleptic tests of instant porridge and cookies using under fiveyear children respondents, it was proven that 93% of children was like the products. Proximate analysis of instant porridge revealed that protein content was 11.04 %, water content was 5.03%,fat content was 1.92 % and ash was 0.64 %. However, proximate analysis showed that cookiesowned protein of 9.11%, fat of 17.03% , water content was 3.93% and ash of 1.38%.Keywords : Encaptulated fish, street food, patin fish protein concentrate, palm oil

Isolation and characterization of starch from industrial fresh pasta by-product and its potential use in sugar-snap cookie making.

Science.gov (United States)

Ellouzi, Soumaya Zouari; Driss, Dorra; Maktouf, Sameh; Neifar, Mohamed; Kobbi, Ameni; Kamoun, Hounaida; Chaabouni, Semia Ellouze; Ghorbel, Raoudha Ellouze

2015-09-01

In this paper, starch was extracted from fresh pasta by-product (PS) and its chemical composition and physical and microscopic characteristics were determined. Commercial wheat starch (CS) was used as reference. In general, purity was similar between starches studied. However, others compounds such as protein, lipid and ash were significantly different. PS starch granules had large lenticular-shape (25-33 μm) and small spherical-shape (5-8 μm). The pH and color of PS starch were similar to those reported for CS starch. On the other hand, PS had higher water absorption capacity, viscosity and cooking stability than CS. The gelatinization temperature of PS was similar to that of CS (60 and 61 °C). At high temperature (90 °C) both starches had similar rheological behavior. The results achieved suggest that PS starch has potential for application in food systems requiring high processing temperatures such the manufacture of sugar snap cookie. The effects of PS starch addition on the dough making stage and the final cookie quality were analyzed. Improvements in dough cohesiveness (24 %) and springiness (10 %) were significant relative to those of CS dough. Texture profile analysis confirmed the rheological changes.

Expression and significance of TRAIL and NF-kB in osteosarcoma

International Nuclear Information System (INIS)

Du Xiumin; You Murong; Qi Falian; Hu Chengjin

2005-01-01

To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

Direct non transcriptional role of NF-Y in DNA replication.

Science.gov (United States)

Benatti, Paolo; Belluti, Silvia; Miotto, Benoit; Neusiedler, Julia; Dolfini, Diletta; Drac, Marjorie; Basile, Valentina; Schwob, Etienne; Mantovani, Roberto; Blow, J Julian; Imbriano, Carol

2016-04-01

NF-Y is a heterotrimeric transcription factor, which plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation, apoptosis and DNA damage response. The knock-down of the sequence-specific subunit NF-YA triggers defects in S-phase progression, which lead to apoptotic cell death. Here, we report that NF-Y has a critical function in DNA replication progression, independent from its transcriptional activity. NF-YA colocalizes with early DNA replication factories, its depletion affects the loading of replisome proteins to DNA, among which Cdc45, and delays the passage from early to middle-late S phase. Molecular combing experiments are consistent with a role for NF-Y in the control of fork progression. Finally, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication, specifically in the DNA elongation process, using a Xenopus cell-free system. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific TFs required for proper and efficient DNA replication. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function

International Nuclear Information System (INIS)

Zhao Guohua; Shi Lingfang; Qiu Daoming; Hu Hong; Kao, Peter N.

2005-01-01

NF45/ILF2 associates with NF90/ILF3 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence (P.N. Kao, L. Chen, G. Brock, J. Ng, A.J. Smith, B. Corthesy, J. Biol. Chem. 269 (1994) 20691-20699). NF45 is widely expressed in normal tissues, especially testis, brain, and kidney, with a predominantly nuclear distribution. NF45 mRNA expression is increased in lymphoma and leukemia cell lines. The human and murine NF45 proteins differ only by substitution of valine by isoleucine at amino acid 142. Fluorescence in situ hybridization localized the human NF45 gene to chromosome 1q21.3, and mouse NF45 gene to chromosome 3F1. Promoter analysis of 2.5 kB of the murine NF45 gene reveals that significant activation is conferred by factors, possible including NF-Y, that bind to the CCAAT-box sequence. The function of human NF45 in regulating IL-2 gene expression was characterized in Jurkat T-cells stably transfected with plasmids directing expression of NF45 cDNA in sense or antisense orientations. NF45 sense expression increased IL-2 luciferase reporter gene activity 120-fold, and IL-2 protein expression 2-fold compared to control cells. NF45 is a highly conserved, regulated transcriptional activator, and one target gene is IL-2

Development of functional cookies with wheat flour, banana flour (Musa paradisiaca, sesame seeds (Sesamum indicum and storage stability

Directory of Open Access Journals (Sweden)

Angélica Loza

2017-01-01

Full Text Available Functional cookies were developed using banana flour (BF and sesame seeds (SS. Protein, moisture and ash w ere determined , and farinographic analyzes of flours were performed. The attributes odor, color, flavor, crunch and the IC 50 value of the cookies were determined. The results were evaluated with the C omplete R andomized D esign and the Tukey and Kruskall Wallis test. The flour mixture presented higher protein (10.2%, humidity (14.40 % than BF, but lower than wheat flour. C ookies with 10 % , 15 % and 20% BF and 8% sesame seeds were selected. Flours with 10 % , 15 % and 20% BF had similar values of water absorption (≤ 60% and different values statistically (p ≤ 0.05 for development time, mass stability and degree of softening. Cook ies with 20% BF and 8% SS (SC had IC 50 = 17.52 ± 0.25 mg / mL, with moisture, protein, fat, crude fiber, ash and carbohydrates of 1.88 % , 10.65 % , 22.01 % , 1.01 % , 1.54 % and 62.91%, respectively. SC did not present sensorial statistical differences (p ≤ 0.05 the first two months, the third month decreased the acceptability of the crunch and flavor. In ninety days of storage the IC50 value (29.07 ± 0.92 mg / mL, reducing sugars (1.20 ± 0.02 and pH (5.24 ± 0.01 decreased and humidity (3.83 ± 0.03 increased.

Porcine arterivirus activates the NF-κB pathway through IκB degradation

International Nuclear Information System (INIS)

Lee, Sang-Myeong; Kleiboeker, Steven B.

2005-01-01

Nuclear factor-kappaB (NF-κB) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-κB in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-κB activation was characterized by translocation of NF-κB from the cytoplasm to the nucleus, increased DNA binding activity, and NF-κB-regulated gene expression. NF-κB activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-κB activation. Degradation of IκB protein was detected late in PRRSV infection, and overexpression of the dominant negative form of IκBα (IκBαDN) significantly suppressed NF-κB activation induced by PRRSV. However, IκBαDN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-κB DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-κB was activated by PRRSV infection. Moreover, NF-κB-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-κB activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV

Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?

Science.gov (United States)

Ravasco, Paula; Aranha, Márcia M; Borralho, Pedro M; Moreira da Silva, Isabel B; Correia, Luís; Fernandes, Afonso; Rodrigues, Cecília M P; Camilo, Maria

2010-02-01

NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness. Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay. NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002). NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Effect of reducing agents on wheat gluten and quality characteristics of flour and cookies

Directory of Open Access Journals (Sweden)

Naveen KUMAR

2013-12-01

Full Text Available The aim of the present study was to determine the effect of reducing agents (Lcystine, glutathione and proteases on wheat gluten recovery and quality characteristics of dough and cookies. PBW-343 and RAJ-3765 wheat varieties were analysed for physico-chemical properties which indicated that wheat variety RAJ-3765 had superior quality characteristics in comparison to PBW-343. Wet gluten and dry gluten %yields were reduced with addition of reducing agents. As the concentration of reducing agents increased gluten, yield decreased further. The dough strength (resistance to extension decreased, whereas extension of dough increased significantly with the addition of reducing agents. Upon addition of reducing agents, spread factor increased, whereas hardness decreased. Glutathione was found to be the most effective reducing agent out of the three reducing agents used in this study.

Instanton dominance over αs at low momenta from lattice QCD simulations at Nf = 0, Nf = 2 + 1 and Nf = 2 + 1 + 1

Science.gov (United States)

Athenodorou, Andreas; Boucaud, Philippe; de Soto, Feliciano; Rodríguez-Quintero, José; Zafeiropoulos, Savvas

2018-03-01

We report on an instanton-based analysis of the gluon Green functions in the Landau gauge for low momenta; in particular we use lattice results for αs in the symmetric momentum subtraction scheme (MOM) for large-volume lattice simulations. We have exploited quenched gauge field configurations, Nf = 0, with both Wilson and tree-level Symanzik improved actions, and unquenched ones with Nf = 2 + 1 and Nf = 2 + 1 + 1 dynamical flavors (domain wall and twisted-mass fermions, respectively). We show that the dominance of instanton correlations on the low-momenta gluon Green functions can be applied to the determination of phenomenological parameters of the instanton liquid and, eventually, to a determination of the lattice spacing. We furthermore apply the Gradient Flow to remove short-distance fluctuations. The Gradient Flow gets rid of the QCD scale, ΛQCD, and reveals that the instanton prediction extents to large momenta. For those gauge field configurations free of quantum fluctuations, the direct study of topological charge density shows the appearance of large-scale lumps that can be identified as instantons, giving access to a direct study of the instanton density and size distribution that is compatible with those extracted from the analysis of the Green functions.

Transcription Factor NF-κB: An Update on Intervention Strategies.

Science.gov (United States)

Panday, Arvind; Inda, Maria Eugenia; Bagam, Prathyusha; Sahoo, Malaya K; Osorio, Diana; Batra, Sanjay

2016-12-01

The nuclear factor (NF)-κB family of transcription factors are ubiquitous and pleiotropic molecules that regulate the expression of more than 150 genes involved in a broad range of processes including inflammation, immunity, cell proliferation, differentiation, and survival. The chronic activation or dysregulation of NF-κB signaling is the central cause of pathogenesis in many disease conditions and, therefore, NF-κB is a major focus of therapeutic intervention. Because of this, understanding the relationship between NF-κB and the induction of various downstream signaling molecules is imperative. In this review, we provide an updated synopsis of the role of NF-κB in DNA repair and in various ailments including cardiovascular diseases, HIV infection, asthma, herpes simplex virus infection, chronic obstructive pulmonary disease, and cancer. Furthermore, we also discuss the specific targets for selective inhibitors and future therapeutic strategies.

Motor dysfunction in NF1: Mediated by attention deficit or inherent to the disorder?

Science.gov (United States)

Haas-Lude, Karin; Heimgärtner, Magdalena; Winter, Sarah; Mautner, Victor-Felix; Krägeloh-Mann, Ingeborg; Lidzba, Karen

2018-01-01

Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance. Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6-12 years. There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1. Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The handwriting performance of children with NF1.

Science.gov (United States)

Gilboa, Yafit; Josman, Naomi; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Rosenblum, Sara

2010-01-01

The objective of this study was to analyze the process and product of handwriting among children with Neurofibromatosis Type 1 (NF1) in comparison to those of Typically Developing (TD) children. Children with NF1 are at risk for some cognitive deficits, a wide range of deficits in perceptual skills and, motor and visual-motor integration skills which may interfere with handwriting competency, which is an essential ingredient for success at school. Participants were 30 NF1 children and 30 age and gender matched TD children, between the ages 8 and 16.08. The handwriting performance of children with NF1 was evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), for copying text and free style writing tasks, using: (1) Computerized Penmanship Evaluation Tool (ComPET) to assess mechanical aspects of the writing process. (2) The Hebrew Handwriting Evaluation (HHE) to examine product legibility. (3) The Six-Trait Writing Model to judge the quality of the written product. Significant differences between the NF1 children and the control group were found in the process and product measures. Significant correlations were found between the VMI, the ComPET, the HHE and the Six-Trait Writing Model variables for both groups. We suggest a possible relationship between executive dysfunction and poor performance in handwriting.

NF1 Signal Transduction and Vascular Dysfunction

Science.gov (United States)

2015-05-01

microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis.

Science.gov (United States)

Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Park, Daeui; Kim, Dae Hyun; Choi, Yeun Ja; Lee, Eun Kyeong; Kim, Kyung Mok; Park, June Whoun; Yu, Byung Pal; Chung, Hae Young

2017-01-31

Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-κBIZ (also known as IκBζ) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-κBIZ and of IL-6 and MCP-1 (both known to be regulated by NF-κBIZ) during aging. The up-regulation of NF-κBIZ in aged rat kidneys coincided with increased macrophage infiltration. In LPS-treated macrophages, oxidative stress was found to play a pivotal role in NF-κBIZ expression, suggesting age-related oxidative stress is associated with NF-κBIZ activation. Furthermore, these in vitro findings were confirmed in LPS-treated old rats, which showed higher levels of oxidative stress and NF-κBIZ in kidneys than LPS-treated young rats. Additional in vitro experiments using macrophages and kidney fibroblasts demonstrated NF-κBIZ and related cytokines participate in fibrosis. In particular, increased levels of NF-κBIZ-associated cytokines in macrophages significantly up-regulated TGF-β induced kidney fibroblast activation. Moreover, experiments with NF-κBIZ knocked down macrophages showed reduced TGF-β-induced kidney fibroblast activation. The findings of the present study provide evidence regarding an involvement of NF-κBIZ in age-associated progressive renal fibrosis and provides potential targets for its prevention.

Making Research Delicious: An Evaluation of Nurses' Knowledge, Attitudes, and Practice Using the Great American Cookie Experiment With Mobile Device Gaming.

Science.gov (United States)

Hayes Lane, Susan; Serafica, Reimund; Huffman, Carolyn; Cuddy, Alyssa

2016-01-01

In the current healthcare environment, nurses must have a basic understanding of research to lead change and implement evidence-based practice. The purpose of this study was to evaluate the effectiveness of an educational intervention formulated on the framework of the Great American Cookie Experiment measuring nurses' research knowledge, attitudes, and practice using mobile device gaming. This multisite quantitative study provides insight into promotion of research and information about best practices on innovative teaching strategies for nurses.

A Comparative Study of Partial Replacement of Wheat Flour with Whey and Soy Protein on Rheological Properties of Dough and Cookie Quality

Directory of Open Access Journals (Sweden)

Xiaozhi Tang

2017-01-01

Full Text Available The development of wheat-based foods that are enriched with proteins is increasingly popular. The purpose of this study was to compare the effects of partial replacement of wheat flour with whey and soy proteins (0–30% on the rheological properties of dough and cookie-making quality. The incorporation of whey protein (WP diluted the concentration of gluten, leading to an increase in dough development time (MDT and breakdown torque and a decrease in stability time (MST and minimum torque (MMT. The gelation of WP during the heat treatment increased dough peak torque (MPT, G′, and G′′. As a contrast, the addition of soy protein (SP increased dough MST, MDT, and MMT. The aggregation of SP helped increase G′ and decrease tan δ of the dough in oscillatory shear tests. The weak gelling effects and higher water absorption of SP decreased MPT, G′, and G′′ of the dough during heat treatment. With SP, the spread ratio of cookies first decreased from 6.39 to 5.66 and then increased to 6.86, and the overall acceptability scores ranged from 6.62 to 7.02, indicating that the formed soy protein network helped maintain the dough structure for obtaining an improvement in the quality of bakery products.

NF-1 Dependent Gene Regulation in Drosophila Melanogaster

Science.gov (United States)

2004-04-01

standard cornmeal medium at 25oC in a humidified incubator. Flies were collected and frozen in liquid nitrogen at the same time of day to minimize...melanogaster media, strains and heat-shock conditions Flies were raised at room temperature (22–248C) on standard cornmeal medium. The Nf1 mutants Nf1P1 and

How the projection domains of NF-L and alpha-internexin determine the conformations of NF-M and NF-H in neurofilaments

NARCIS (Netherlands)

Leermakers, F.A.M.; Zhulina, E.B.

2010-01-01

Making use of a numerical self-consistent field method and polymer brush concepts, we model the solvated corona of neurofilaments (NF) composed of projection domains (unstructured tails) of constituent proteins. Projections are modeled with amino acid resolution. We focus on the importance of the

NF-kappaB mediates FGF signal regulation of msx-1 expression.

Science.gov (United States)

Bushdid, P B; Chen, C L; Brantley, D M; Yull, F; Raghow, R; Kerr, L D; Barnett, J V

2001-09-01

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic Press.

Towards continuous global measurements and optimal emission estimates of NF3

Science.gov (United States)

Arnold, T.; Muhle, J.; Salameh, P.; Harth, C.; Ivy, D. J.; Weiss, R. F.

2011-12-01

We present an analytical method for the continuous in situ measurement of nitrogen trifluoride (NF3) - an anthropogenic gas with a global warming potential of ~16800 over a 100 year time horizon. NF3 is not included in national reporting emissions inventories under the United Nations Framework Convention on Climate Change (UNFCCC). However, it is a rapidly emerging greenhouse gas due to emission from a growing number of manufacturing facilities with increasing output and modern end-use applications, namely in microcircuit etching, and in production of flat panel displays and thin-film photovoltaic cells. Despite success in measuring the most volatile long lived halogenated species such as CF4, the Medusa preconcentration GC/MS system of Miller et al. (2008) is unable to detect NF3 under remote operation. Using altered techniques of gas separation and chromatography after initial preconcentration, we are now able to make continuous atmospheric measurements of NF3 with average precisions NF3 produced. Emission factors are shown to have reduced over the last decade; however, rising production and end-use have caused the average global atmospheric concentration to double between 2005 and 2011 i.e. half the atmospheric NF3 present today originates from emissions after 2005. Finally we show the first continuous in situ measurements from La Jolla, California, illustrating how global deployment of our technique could improve the temporal and spatial scale of NF3 'top-down' emission estimates over the coming years. These measurements will be important for independent verification of emissions should NF3 be regulated under a new climate treaty.

Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

Science.gov (United States)

Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

2012-01-01

The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

TEffect of nf-kappa B on diabetic retinopathy%NF-κB对糖尿病视网膜病变的影响

Institute of Scientific and Technical Information of China (English)

王爽; 宋子宣

2015-01-01

目的 研究和探讨核因子κB (NF-κ B)在糖尿病视网膜病变中的作用.方法 首先建立糖尿病视网膜病变(DR,diabetic retinopathy)动物模型,雄性SD大鼠,链脲佐菌素(streptozotocin,STZ) 60 mg/kg腹腔注射形成糖尿病模型,1.5个月后SD大鼠玻璃体内行血管内皮生长因子(VEGF)注射造成增殖型的糖尿病视网膜病变模型.视网膜铺片使用ADP酶染色视网膜血管,实时定量PCR检测NF-κ B表达量的变化,以及凋亡信号的检测.结果 视网膜血管染色的增殖面积造模给水组为(12.0±4.1)％,而视网膜血管染色的无灌注区面积造模给NF-κ B拮抗剂组为(37.9±3.9)％.正常组大鼠的NF-κ B蛋白的灰度值为(194.2890±3.8900),而造模给水组的NF-κB蛋白的灰度值为(74.4300±4.4900),凋亡实验结果显示正常组大鼠的凋亡信号个数平均为(32.2±3.1),而造模给水组的凋亡信号个数平均为(7.4±4.2).结论 NF-κB主要是通过引起细胞凋亡而减少糖尿病视网膜病变患者视网膜血管的增殖.%Objective To study the effect of nuclear factor kappa B (nf-kappa B) on diabetic retinopathy.Methods Diabetic retinopathy (DR,diabetic retinopathy) animal models were established.The SD rats intraperitoneal injected 60 cephalosporins (STZ streptozotocin) mg/kg to form diabetes models; 1.5 months from then,the SD rats were vitreously injected vascular endothelial growth factor (VEGF) to build models of proliferative diabetic retinopathy[l].Retinal blood vessels stained by ADP enzyme were used as retinal pave pieces.Real-time quantitative PCR was used to detect the e change of nf-kappa B expression quantity and apoptosis signal.Results The proliferation area of dyed retinal vessels of the model-buildingwith-water group was (12.0±4.1)％.The area without perfusion of dyed retinal blood vessels of the modelbuilding-with-nf-kappa-B-antagonist group was (37.9 ± 3.9)％.The gray value of nf-kappa B protein was (194.2890 ± 3.8900) in the

A requirement for NF-κB in developmental and plasticity-associated synaptogenesis

Science.gov (United States)

Boersma, Matthew C. H.; Dresselhaus, Erica C.; De Biase, Lindsay M.; Mihalas, Anca B.; Bergles, Dwight E.

2011-01-01

Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits and may form an enduring basis for information storage in the brain. We find that the p65 subunit of the NF-κB transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-κB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in-vitro synaptogenesis, NF-κB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-κB within the postsynaptic neuron is sufficient to regulate the formation of both pre- and post-synaptic elements. During synapse development in-vivo, loss of NF-κB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-κB activity is low and p65-deficiency no longer attenuates basal spine density. Instead, NF-κB in mature neurons is activated by stimuli that induce demand for new synapses, including estrogen and short-term bicuculline, and is essential for upregulating spine density in response to these stimuli. p65 is enriched in dendritic spines making local protein-protein interactions possible; however, the effects of NF-κB on spine density require transcription and the NF-κB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-κB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density. PMID:21471377

2006 marketplace survey of trans-fatty acid content of margarines and butters, cookies and snack cakes, and savory snacks.

Science.gov (United States)

Albers, Matthew J; Harnack, Lisa J; Steffen, Lyn M; Jacobs, David R

2008-02-01

In recent years, newer technologies have been developed to reduce the trans-fat content of fats and oils used in manufacturing food products. To examine the implications of these changes on foods in the marketplace, a survey was conducted to assess current levels of trans and saturated fat in three food categories: margarines and butters; cookies and snack cakes; and savory snacks. A sampling of products from each category was conducted at a Wal-Mart Supercenter in the Minneapolis-St Paul, MN, metropolitan area in July of 2006. All information was obtained from product labels, except price, which was recorded from price listings on product shelving. Most margarines and butters (21 of 29), cookies and snack cakes (34 of 44), and savory snacks (31 of 40) were labeled as containing 0 g trans fat. However, some products contained substantial amounts of trans fat. Most notably, 3 of 40 savory snack products were labeled as containing > or =3 g trans fat. Significant inverse correlations were found between product price and the saturated and trans-fat content of margarines (r=-0.45) and savory snacks (r=-0.32). In conclusion, it appears that the food industry has made progress in reducing the trans-fat content in a variety of products. Nonetheless, consumers need to read product labels because the trans-fat content of individual products can vary considerably. Products that are lower in trans and saturated fat tend to cost more, which may be a barrier to their purchase for price-conscious consumers.

RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway

International Nuclear Information System (INIS)

Shimada, Kana; Saeki, Makio; Egusa, Hiroshi; Fukuyasu, Sho; Yura, Yoshiaki; Iwai, Kazuhiro; Kamisaki, Yoshinori

2011-01-01

Research highlights: → RNA polymerase II-associated protein 3 (RPAP3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO. → RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. → RPAP3 is a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents. -- Abstract: Activation of anti-apoptotic gene transcription by NF-κB (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-κB essential modulator) interacts with a number of proteins and modulates the activity of NF-κB pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. These results indicate that RPAP3 may be a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents.

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2008-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2007-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

Interactions among oscillatory pathways in NF-kappa B signaling

Directory of Open Access Journals (Sweden)

White Michael RH

2011-02-01

Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

A role for NF-κB–dependent gene transactivation in sunburn

Science.gov (United States)

Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

2000-01-01

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

DNA-dependent protein kinase participates in the radiation activation of NF-kB

International Nuclear Information System (INIS)

Rosenzweig, Kenneth E.; Youmell, Matthew B.; Price, Brendan D.

1997-01-01

The NF-kB transcription factor is maintained in an inactive state by binding to the lkBa inhibitory protein. Activation requires phosphorylation and degradation of lkBa, releasing active NF-kB. NF-kB can be activated by cytokines, antigens, free radicals and X-ray irradiation. The protein kinase responsible for phosphorylation of lkBa in vivo has not been fully characterized. Here, we have examined the role of the DNA-dependent protein kinases (DNA-PK) in the radiation-activation of NF-kB. Wortmannin is an inhibitor of DNA-PK and related kinases. Exposure of SW480 cells to wortmannin inhibited the radioactivation of NF-kB DNA-binding. Analysis of lkBa levels by western blotting indicated that wortmannin blocked the radiation induced degradation of lkBa. In in vitro experiments, purified DNA-PK was able to efficiently phosphorylate lkBa, and this phosphorylation was inhibited by wortmannin. In contrast, the induction of NF-kB activity by TNFa was unaffected by wortmannin. The results suggest that DNA-PK may phosphorylate lkBa following irradiation, leading to degradation of lkBa and the release of active NF-kB. The inability of wortmannin to block TNFa activation of NF-kB indicates there may be more than one pathway for the activation of NF-kB

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Genotype-Phenotype Correlation in NF1: Evidence for a More Severe Phenotype Associated with Missense Mutations Affecting NF1 Codons 844–848

NARCIS (Netherlands)

Koczkowska, M. (Magdalena); Chen, Y. (Yunjia); Callens, T. (Tom); Gomes, A. (Alicia); Sharp, A. (Angela); Johnson, S. (Sherrell); Hsiao, M.-C. (Meng-Chang); Chen, Z. (Zhenbin); Balasubramanian, M. (Meena); Barnett, C.P. (Christopher P.); Becker, T.A. (Troy A.); Ben-Shachar, S. (Shay); D.R. Bertola (Débora Romeo); J.O. Blakeley (Jaishri O.); Burkitt-Wright, E.M.M. (Emma M.M.); Callaway, A. (Alison); Crenshaw, M. (Melissa); Cunha, K.S. (Karin S.); Cunningham, M. (Mitch); M.D. D'Agostino (Maria Daniela); K. Dahan (Karin); De Luca, A. (Alessandro); A. Destrée (Anne); Dhamija, R. (Radhika); Eoli, M. (Marica); Evans, D.G.R. (D. Gareth R.); Galvin-Parton, P. (Patricia); George-Abraham, J.K. (Jaya K.); K.W. Gripp (Karen); Guevara-Campos, J. (Jose); Hanchard, N.A. (Neil A.); Hernández-Chico, C. (Concepcion); Immken, L. (LaDonna); S. Janssens (Sandra); K.J. Jones (Kristi); Keena, B.A. (Beth A.); Kochhar, A. (Aaina); Liebelt, J. (Jan); Martir-Negron, A. (Arelis); Mahoney, M.J. (Maurice J.); I. Maystadt (Isabelle); McDougall, C. (Carey); M. McEntagart (Meriel); N.J. Mendelsohn; Miller, D.T. (David T.); G. Mortier (Geert); J. Morton (Jenny); Pappas, J. (John); S.R. Plotkin (Scott R.); Pond, D. (Dinel); Rosenbaum, K. (Kenneth); Rubin, K. (Karol); Russell, L. (Laura); Rutledge, L.S. (Lane S.); Saletti, V. (Veronica); Schonberg, R. (Rhonda); Schreiber, A. (Allison); Seidel, M. (Meredith); Siqveland, E. (Elizabeth); D.W. Stockton (David); Trevisson, E. (Eva); N.J. Ullrich (Nicole J.); M. Upadhyaya (Meena); A.S. Thornton (Andrew); H. Verhelst (H.); M.R. Wallace (Margaret); Yap, Y.-S. (Yoon-Sim); Zackai, E. (Elaine); Zonana, J. (Jonathan); Zurcher, V. (Vickie); K. Claes (Kathleen); Martin, Y. (Yolanda); B. Korf (Bruce); E. Legius (Eric); L.M. Messiaen (Ludwine)

2018-01-01

textabstractNeurofibromatosis type 1 (NF1), a common genetic disorder with a birth incidence of 1:2,000–3,000, is characterized by a highly variable clinical presentation. To date, only two clinically relevant intragenic genotype-phenotype correlations have been reported for NF1 missense mutations

THE ROLE OF NF-κB IN NEURONAL PLASTICITY AND NEURODEGENERATIVE DISEASES

OpenAIRE

Yağmur, Elif Nuran; Yıldız, Nazım; Adıgüzel, Serkan; Femir, Banu; Şenyer, Seray; Şen, Melis; Tüzün, Erdem; Küçükali, Cem İsmail

2018-01-01

NF-κB is a transcription factor emerged by the end of 20th century. At the beginning, NF-κB wasfound to be present in immune cells but following studies showed its presence in almost all cells inan organism. NF-κB takes part in the activation of almost 500 genes and have roles in mechanismsincluding immune response, cell cycle, cell survival, cell proliferation and development, as well asplasticity and memory formation. Long-term potentiation (LTP) of NF-κB in the central nervoussystem (CNS) ...

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

Directory of Open Access Journals (Sweden)

Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

Science.gov (United States)

Zhao, Fei; Zhang, ShiJiang; Chen, YiJiang; Gu, WeiDong; Ni, BuQing; Shao, YongFeng; Wu, YanHu; Qin, JianWei

2014-11-25

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

Instanton dominance over $a_s$ at low momenta from lattice QCD simulations at $N_f=0$, $N_f=2+1$ and $N_f=2+1+1$

Energy Technology Data Exchange (ETDEWEB)

Athenodorou, Andreas [Cyprus Institute, Nicosia, Cyprus; Boucaud, Philippe [Univ. Paris-Sud, Orsay (France); de Soto, Feliciano [Univ. Pablo de Olavide, 41013 Sevilla; Spain; Univ. of Granada (Spain); Rodriguez-Quintero, Jose [Universidad de Huelva, 21071 Huelva; Spain; Univ. of Granada (Spain); Zafeiropoulos, Savvas [College of William and Mary, Williamsburg, VA (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Heidelberg Univ. (Germany). Inst. for Theoretische Physik

2018-04-01

We report on an instanton-based analysis of the gluon Green functions in the Landau gauge for low momenta; in particular we use lattice results for αs in the symmetric momentum subtraction scheme (MOM) for large-volume lattice simulations. We have exploited quenched gauge field configurations, Nf = 0, with both Wilson and tree-level Symanzik improved actions, and unquenched ones with Nf = 2 + 1 and Nf = 2 + 1 + 1 dynamical flavors (domain wall and twisted-mass fermions, respectively).We show that the dominance of instanton correlations on the low-momenta gluon Green functions can be applied to the determination of phenomenological parameters of the instanton liquid and, eventually, to a determination of the lattice spacing.We furthermore apply the Gradient Flow to remove short-distance fluctuations. The Gradient Flow gets rid of the QCD scale, ΛQCD, and reveals that the instanton prediction extents to large momenta. For those gauge field configurations free of quantum fluctuations, the direct study of topological charge density shows the appearance of large-scale lumps that can be identified as instantons, giving access to a direct study of the instanton density and size distribution that is compatible with those extracted from the analysis of the Green functions.

Post-Translational Modifications of RelB NF-κB Subunit and Associated Functions

Directory of Open Access Journals (Sweden)

Véronique Baud

2016-05-01

Full Text Available The family of NF-κB transcription factors plays a key role in diverse biological processes, such as inflammatory and immune responses, cell survival and tumor development. Beyond the classical NF-κB activation pathway, a second NF-κB pathway has more recently been uncovered, the so-called alternative NF-κB activation pathway. It has been shown that this pathway mainly controls the activity of RelB, a member of the NF-κB family. Post-translational modifications, such as phosphorylation, acetylation, methylation, ubiquitination and SUMOylation, have recently emerged as a strategy for the fine-tuned regulation of NF-κB. Our review discusses recent progress in the understanding of RelB regulation by post-translational modifications and the associated functions in normal and pathological conditions.

NF-kappaB signaling: a tale of two pathways in skeletal myogenesis.

Science.gov (United States)

Bakkar, Nadine; Guttridge, Denis C

2010-04-01

NF-kappaB is a ubiquitiously expressed transcription factor that plays vital roles in innate immunity and other processes involving cellular survival, proliferation, and differentiation. Activation of NF-kappaB is controlled by an IkappaB kinase (IKK) complex that can direct either canonical (classical) NF-kappaB signaling by degrading the IkappaB inhibitor and releasing p65/p50 dimers to the nucleus, or causes p100 processing and nuclear translocation of RelB/p52 via a noncanonical (alternative) pathway. Under physiological conditions, NF-kappaB activity is transiently regulated, whereas constitutive activation of this transcription factor typically in the classical pathway is associated with a multitude of disease conditions, including those related to skeletal muscle. How NF-kappaB functions in muscle diseases is currently under intense investigation. Insight into this role of NF-kappaB may be gained by understanding at a more basic level how this transcription factor contributes to skeletal muscle cell differentiation. Recent data from knockout mice support that the classical NF-kappaB pathway functions as an inhibitor of skeletal myogenesis and muscle regeneration acting through multiple mechanisms. In contrast, alternative NF-kappaB signaling does not appear to be required for myofiber conversion, but instead functions in myotube homeostasis by regulating mitochondrial biogenesis. Additional knowledge of these signaling pathways in skeletal myogenesis should aid in the development of specific inhibitors that may be useful in treatments of muscle disorders.

ESTUDO TEÓRICO DAS PROPRIEDADES CINÉTICAS DA REAÇÃO NF+F = N+F2

OpenAIRE

Prado, Danielle Maria Fernandes do; Instituto Federal de Educação, Ciência e Tecnologia de Goiás; Ramalho, Simone Souza

2010-01-01

O principal objetivo dos estudos com o Trifluoreto de nitrogênio é estudar a dissociação deste em nitrogênio e flúor. Para o entendimento e a determinação do correto caminho de dissociação do NF3, é necessário estudar uma série de reações elementares, como passo intermediário para alcançar a reação global deste sistema. Neste projeto é apresentado uma proposta de determinação das propriedades cinéticas e dinâmicas das reações envolvidas nos mecanismos de dissociação do NF3 . Para a realização...

Flour mill stream blending affects sugar snap cookie and Japanese sponge cake quality and oxidative cross-linking potential of soft white wheat.

Science.gov (United States)

Ramseyer, Daniel D; Bettge, Arthur D; Morris, Craig F

2011-01-01

The purpose of this research was to study the functional differences between straight grade (75% extraction rate) and patent (60% extraction rate) flour blends from 28 genetically pure soft white and club wheat grain lots, as evidenced by variation in sugar snap cookie and Japanese sponge cake quality. Functional differences were examined relative to arabinoxylan content, protein content, and oxidative cross-linking potential of flour slurries. Oxidative cross-linking measurements were obtained on flour slurries with a low shear Bostwick consistometer and considered endogenous oxidative cross-linking potential (water alone) or enhanced oxidative cross-linking potential (with added hydrogen peroxide-peroxidase). A 2-way ANOVA indicated that flour blend was the greater source of variation compared to grain lot for all response variables except water-extractable arabinoxylan content. Patent flours produced larger sugar snap cookies and Japanese sponge cakes, and contained significantly less total and water-unextractable arabinoxylans, protein, and ash than did straight grade flours. Patent flours produced more viscous slurries for endogenous and enhanced cross-linking measurements compared to the straight grade flours. The functional differences between patent and straight grade flours appear to be related to the particular mill streams that were utilized in the formulation of the 2 flour blends and compositional differences among those streams. Journal of Food Science © 2011 Institute of Food Technologists® No claim to original US government works.

42 CFR 483.114 - Annual review of NF residents.

Science.gov (United States)

2010-10-01

... residents. (a) Individuals with mental illness. For each resident of a NF who has mental illness, the State... physical and mental condition, the resident requires— (1) The level of services provided by— (i) A NF; (ii... 65 or older; and (2) Specialized services for mental illness, as defined in § 483.120. (b...

Identification of a novel TIF-IA-NF-κB nucleolar stress response pathway.

Science.gov (United States)

Chen, Jingyu; Lobb, Ian T; Morin, Pierre; Novo, Sonia M; Simpson, James; Kennerknecht, Kathrin; von Kriegsheim, Alex; Batchelor, Emily E; Oakley, Fiona; Stark, Lesley A

2018-06-05

p53 as an effector of nucleolar stress is well defined, but p53 independent mechanisms are largely unknown. Like p53, the NF-κB transcription factor plays a critical role in maintaining cellular homeostasis under stress. Many stresses that stimulate NF-κB also disrupt nucleoli. However, the link between nucleolar function and activation of the NF-κB pathway is as yet unknown. Here we demonstrate that artificial disruption of the PolI complex stimulates NF-κB signalling. Unlike p53 nucleolar stress response, this effect does not appear to be linked to inhibition of rDNA transcription. We show that specific stress stimuli of NF-κB induce degradation of a critical component of the PolI complex, TIF-IA. This degradation precedes activation of NF-κB and is associated with increased nucleolar size. It is mimicked by CDK4 inhibition and is dependent upon a novel pathway involving UBF/p14ARF and S44 of the protein. We show that blocking TIF-IA degradation blocks stress effects on nucleolar size and NF-κB signalling. Finally, using ex vivo culture, we show a strong correlation between degradation of TIF-IA and activation of NF-κB in freshly resected, human colorectal tumours exposed to the chemopreventative agent, aspirin. Together, our study provides compelling evidence for a new, TIF-IA-NF-κB nucleolar stress response pathway that has in vivo relevance and therapeutic implications.

Large-nf contributions to the four-loop splitting functions in QCD

Directory of Open Access Journals (Sweden)

J. Davies

2017-02-01

Full Text Available We have computed the fourth-order nf2 contributions to all three non-singlet quark–quark splitting functions and their four nf3 flavour-singlet counterparts for the evolution of the parton distributions of hadrons in perturbative QCD with nf effectively massless quark flavours. The analytic form of these functions is presented in both Mellin N-space and momentum-fraction x-space; the large-x and small-x limits are discussed. Our results agree with all available predictions derived from lower-order information. The large-x limit of the quark–quark cases provides the complete nf2 part of the four-loop cusp anomalous dimension which agrees with two recent partial computations.

Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage

International Nuclear Information System (INIS)

Raveh-Amit, Hadas; Hai, Naama; Rotem-Dai, Noa; Shahaf, Galit; Gopas, Jacob; Livneh, Etta

2011-01-01

Highlights: → Protein kinase C-eta (PKCη) is an upstream regulator of the NF-κB signaling pathway. → PKCη activates NF-κB in non-stressed conditions and in response to DNA damage. → PKCη regulates NF-κB by activating IκB kinase (IKK) and inducing IκB degradation. -- Abstract: The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.

About Learning Disabilities and NF

Science.gov (United States)

... complica- tions of NF1 include: • Learning disabilities: Although intelligence is usually within the normal range, 50-60% ... and the ability to access meaning from the printed word. 5 Recent findings suggest that a high ...

Neuronal RING finger protein 11 (RNF11 regulates canonical NF-κB signaling

Directory of Open Access Journals (Sweden)

Pranski Elaine L

2012-04-01

Full Text Available Abstract Background The RING domain-containing protein RING finger protein 11 (RNF11 is a member of the A20 ubiquitin-editing protein complex and modulates peripheral NF-κB signaling. RNF11 is robustly expressed in neurons and colocalizes with a population of α-synuclein-positive Lewy bodies and neurites in Parkinson disease patients. The NF-κB pathway has an important role in the vertebrate nervous system, where the absence of NF-κB activity during development can result in learning and memory deficits, whereas chronic NF-κB activation is associated with persistent neuroinflammation. We examined the functional role of RNF11 with respect to canonical NF-κB signaling in neurons to gain understanding of the tight association of inflammatory pathways, including NF-κB, with the pathogenesis of neurodegenerative diseases. Methods and results Luciferase assays were employed to assess NF-κB activity under targeted short hairpin RNA (shRNA knockdown of RNF11 in human neuroblastoma cells and murine primary neurons, which suggested that RNF11 acts as a negative regulator of canonical neuronal NF-κB signaling. These results were further supported by analyses of p65 translocation to the nucleus following depletion of RNF11. Coimmunoprecipitation experiments indicated that RNF11 associates with members of the A20 ubiquitin-editing protein complex in neurons. Site-directed mutagenesis of the myristoylation domain, which is necessary for endosomal targeting of RNF11, altered the impact of RNF11 on NF-κB signaling and abrogated RNF11’s association with the A20 ubiquitin-editing protein complex. A partial effect on canonical NF-κB signaling and an association with the A20 ubiquitin-editing protein complex was observed with mutagenesis of the PPxY motif, a proline-rich region involved in Nedd4-like protein interactions. Last, shRNA-mediated reduction of RNF11 in neurons and neuronal cell lines elevated levels of monocyte chemoattractant protein 1 and

Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

Directory of Open Access Journals (Sweden)

D.G. Evans

2016-05-01

Interpretation: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.

Modulation of the NF-kappaB pathway by Bordetella pertussis filamentous hemagglutinin.

Directory of Open Access Journals (Sweden)

Tzvia Abramson

Full Text Available Filamentous hemagglutinin (FHA is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-kappaB transcription factor family in these host cell responses, we examined the effect of FHA on NF-kappaB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection.Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-kappaB pathway, as manifested by the degradation of cytosolic IkappaB alpha, by NF-kappaB DNA binding, and by the subsequent secretion of NF-kappaB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IkappaB alpha, and the failure of TNF-alpha to activate NF-kappaB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells.These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-kappaB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.

A new nonsense mutation in the NF1 gene with neurofibromatosis-Noonan syndrome phenotype.

Science.gov (United States)

Yimenicioğlu, Sevgi; Yakut, Ayten; Karaer, Kadri; Zenker, Martin; Ekici, Arzu; Carman, Kürşat Bora

2012-12-01

Neurofibromatosis-Noonan syndrome is a rare autosomal dominant disorder which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1 gene mutations are reported in the majority of these patients. Sequence analysis of the established genes for Noonan syndrome revealed no mutation; a heterozygous NF1 point mutation c.7549C>T in exon 51, creating a premature stop codon (p.R2517X), had been demonstrated. Neurofibromatosis-Noonan syndrome recently has been considered a subtype of NF1 and caused by different NF1 mutations. We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T in exon 51.

Overexpression of the transcription factor NF-YC9 confers abscisic acid hypersensitivity in Arabidopsis.

Science.gov (United States)

Bi, Chao; Ma, Yu; Wang, Xiao-Fang; Zhang, Da-Peng

2017-11-01

Nuclear factor Y (NF-Y) family proteins are involved in many developmental processes and responses to environmental cues in plants, but whether and how they regulate phytohormone abscisic acid (ABA) signaling need further studies. In the present study, we showed that over-expression of the NF-YC9 gene confers ABA hypersensitivity in both the early seedling growth and stomatal response, while down-regulation of NF-YC9 does not affect ABA response in these processes. We also showed that over-expression of the NF-YC9 gene confers salt and osmotic hypersensitivity in early seedling growth, which is likely to be directly associated with the ABA hypersensitivity. Further, we observed that NF-YC9 physically interacts with the ABA-responsive bZIP transcription factor ABA-INSENSITIVE5 (ABI5), and facilitates the function of ABI5 to bind and activate the promoter of a target gene EM6. Additionally, NF-YC9 up-regulates expression of the ABI5 gene in response to ABA. These findings show that NF-YC9 may be involved in ABA signaling as a positive regulator and likely functions redundantly together with other NF-YC members, and support the model that the NF-YC9 mediates ABA signaling via targeting to and aiding the ABA-responsive transcription factors such as ABI5.

Control y privacidad en el ciberespacio. Uso de las cookies por parte de los principales medios digitales españoles.

OpenAIRE

García Ull, Francisco José

2015-01-01

En marzo de 2012 la legislación española incorporó la directiva comunitaria sobre privacidad electrónica. Desde ese momento, todas las páginas web españolas que recopilan datos a través de cookies y tecnologías similares (siempre que estos archivos no sean estrictamente necesarios para el funcionamiento de la página), tienen la obligación de informar claramente sobre el tipo y la finalidad de los datos recolectados, así como de obtener el consentimiento de los usuarios a destinar sus datos a ...

Pathogenesis of Germline and Somatic NF1 Rearrangements

Science.gov (United States)

1998-10-01

tilt of the occlusal plane upwards to the left and severe malocclusion class II with left cross-bite. Eye examination documented visual acuities of 6...9 on the right and 6/12 on the left, mild hypermetropia, mild amblyopia , divergent strabismus and Lisch nodules. He had minor webbing of the neck... therapy -related myeloid leukemias in Nf +1- mice show both LOH and disomy at the NF1 locus (N. Mahgoub et al, submitted). How do the LOH regions

Constitutive overexpression of the TaNF-YB4 gene in transgenic wheat significantly improves grain yield.

Science.gov (United States)

Yadav, Dinesh; Shavrukov, Yuri; Bazanova, Natalia; Chirkova, Larissa; Borisjuk, Nikolai; Kovalchuk, Nataliya; Ismagul, Ainur; Parent, Boris; Langridge, Peter; Hrmova, Maria; Lopato, Sergiy

2015-11-01

Heterotrimeric nuclear factors Y (NF-Ys) are involved in regulation of various vital functions in all eukaryotic organisms. Although a number of NF-Y subunits have been characterized in model plants, only a few have been functionally evaluated in crops. In this work, a number of genes encoding NF-YB and NF-YC subunits were isolated from drought-tolerant wheat (Triticum aestivum L. cv. RAC875), and the impact of the overexpression of TaNF-YB4 in the Australian wheat cultivar Gladius was investigated. TaNF-YB4 was isolated as a result of two consecutive yeast two-hybrid (Y2H) screens, where ZmNF-YB2a was used as a starting bait. A new NF-YC subunit, designated TaNF-YC15, was isolated in the first Y2H screen and used as bait in a second screen, which identified two wheat NF-YB subunits, TaNF-YB2 and TaNF-YB4. Three-dimensional modelling of a TaNF-YB2/TaNF-YC15 dimer revealed structural determinants that may underlie interaction selectivity. The TaNF-YB4 gene was placed under the control of the strong constitutive polyubiquitin promoter from maize and introduced into wheat by biolistic bombardment. The growth and yield components of several independent transgenic lines with up-regulated levels of TaNF-YB4 were evaluated under well-watered conditions (T1-T3 generations) and under mild drought (T2 generation). Analysis of T2 plants was performed in large deep containers in conditions close to field trials. Under optimal watering conditions, transgenic wheat plants produced significantly more spikes but other yield components did not change. This resulted in a 20-30% increased grain yield compared with untransformed control plants. Under water-limited conditions transgenic lines maintained parity in yield performance. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

MicroRNAs control transcription factor NF-kB (p65) expression in human ovarian cells.

Science.gov (United States)

Sirotkin, Alexander V; Alexa, Richard; Kišová, Gabriela; Harrath, Abdel Halim; Alwasel, Saleh; Ovcharenko, Dmitriy; Mlynček, Miloš

2015-05-01

MicroRNAs (miRNAs) are known to influence ovarian cell proliferation, apoptosis and hormone release, but it remains unknown whether miRNAs affect ovarian functions via transcription factors. We examined the effect of miRNAs on nuclear factor-κappaB (NF-kB) (p65) expression in human ovarian luteinized granulosa cells. We transfected cultured primary human ovarian luteinized granulosa cells with 80 different constructs encoding human pre-miRNAs and then evaluated NF-kB (p65) expression (percentage of cells containing p65) by immunocytochemistry. We found that 21 of the constructs stimulated NF-kB (p65) expression and 18 of the constructs inhibited NF-kB (p65) expression. This is the first direct demonstration that miRNAs affect NF-kB (p65) expression and the first genome-scale miRNA screen to identify upregulation and downregulation of NF-kB accumulation by miRNAs in the ovary. Novel miRNAs that affect the NF-kB signalling pathway could be useful for the control of NF-kB-dependent reproductive processes and the treatment of NF-kB-dependent reproductive disorders.

Imaging MOSS tomographic system for H-1NF

International Nuclear Information System (INIS)

Glass, F.; Howard, J.

1999-01-01

A tomographic diagnostic utilising the Modulated Optical Solid-State spectrometer (MOSS) is planned for the H-1NF stellarator at the ANU. It is designed to create two-dimensional temperature or velocity maps of a poloidal cross-section of the high temperature plasma of H-1NF. The introduction of the MOSS spectrometers has enabled the development of several diagnostics to be used on the H-1NF stellerator. The MOSS spectrometer allows calculations of the plasma temperature and bulk velocity based on a line-integrated measurement of light emitted from electronic transitions within the plasma. A tomographic system utilising a rotatable multi-view ring apparatus and spatial multiplexing through a MOSS spectrometer is currently being developed. The ring apparatus is placed inside the H-1NF vessel and encircles the plasma. Multiple line-of-sight views collect light through a poloidal cross-section of the plasma and the emitted light is coupled into large core optical fibres. The transmitted light, via the optical fibre bundle, is then imaged through a large aperture MOSS spectrometer and onto another optical fibre array. Each fibre is then fed into a photomultiplier tube for signal detection. Characterisation of the properties of the lithium niobate (LiNbO 3 ) crystal used for modulation in the MOSS spectrometer is being undertaken to account for ray divergence in the imaging system. Tomographic techniques enable the construction of a temperature or velocity map of the poloidal cross-section. Rotating the ring apparatus to a new viewing position for the next pulse of plasma should allow an accurate picture to be built up based on the reproducibility of the plasma pulses. It is expected that initial testing of the system will begin in May when H-1NF begins operations at 0.5 Telsa field strength

NF-κB activation impairs somatic cell reprogramming in ageing.

Science.gov (United States)

Soria-Valles, Clara; Osorio, Fernando G; Gutiérrez-Fernández, Ana; De Los Angeles, Alejandro; Bueno, Clara; Menéndez, Pablo; Martín-Subero, José I; Daley, George Q; Freije, José M P; López-Otín, Carlos

2015-08-01

Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-κB activation blocks the generation of iPSCs in ageing. We also show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies.

Utilização da farinha de jatobá (Hymenaea stigonocarpa Mart. na elaboração de biscoitos tipo cookie e avaliação de aceitação por testes sensoriais afetivos univariados e multivariados

Directory of Open Access Journals (Sweden)

SILVA Mara Reis

1998-01-01

Full Text Available Este trabalho teve como objetivo investigar o aproveitamento da farinha de jatobá (Hymenaea stigonocarpa Mart na produção de biscoitos tipo cookie. Inicialmente, foi feita a caracterização química da farinha de jatobá. Em seguida foram elaborados cookies com a proporção de farinha mista de trigo e de jatobá de 9:1 e adição de diferentes tipos de açúcares: açúcar mascavo, açúcar mascavo+mel, mel, frutose e açúcar refinado para a formulação controle. Os cookies foram avaliados nas suas características físicas e sensoriais. O grau de aceitação dos produtos elaborados e alguns produtos comerciais similares foram avaliados por consumidores potenciais do produto em duas regiões geográficas distintas: Campinas (SP e Goiânia (GO. A farinha de jatobá apresentou teores de umidade na faixa de 8,44 a 10,9 g/100g e revelou a seguinte composição em base seca: proteínas 6,2±0,1 g/100g, lipídios 4,04±0,08 g/100g, cinzas 3,38±0,03 g/100g, fibra alimentar solúvel 12,6±0,4 g/100g, fibra alimentar insolúvel 36,4±0,3 g/100g, amido 3,1±0,1 g/100g e açúcares 34,28 g/100g. O cookie elaborado com farinha mista de trigo e jatobá e açúcar mascavo foi o mais aceito entre os produtos testados.

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

OpenAIRE

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase repor...

Functional Analysis of Drosophila NF1

National Research Council Canada - National Science Library

Bernards, Andre

2005-01-01

...) for Ras, yet homozygous loss of a highly conserved Drosophila NF1 ortholog results in several phenotypes that are insensitive to manipulating Ras signal transduction, but rescued by increasing...

Spontaneous NF-κB activation by autocrine TNFα signaling: a computational analysis.

Directory of Open Access Journals (Sweden)

Jakub Pękalski

Full Text Available NF-κB is a key transcription factor that regulates innate immune response. Its activity is tightly controlled by numerous feedback loops, including two negative loops mediated by NF-κB inducible inhibitors, IκBα and A20, which assure oscillatory responses, and by positive feedback loops arising due to the paracrine and autocrine regulation via TNFα, IL-1 and other cytokines. We study the NF-κB system of interlinked negative and positive feedback loops, combining bifurcation analysis of the deterministic approximation with stochastic numerical modeling. Positive feedback assures the existence of limit cycle oscillations in unstimulated wild-type cells and introduces bistability in A20-deficient cells. We demonstrated that cells of significant autocrine potential, i.e., cells characterized by high secretion of TNFα and its receptor TNFR1, may exhibit sustained cytoplasmic-nuclear NF-κB oscillations which start spontaneously due to stochastic fluctuations. In A20-deficient cells even a small TNFα expression rate qualitatively influences system kinetics, leading to long-lasting NF-κB activation in response to a short-pulsed TNFα stimulation. As a consequence, cells with impaired A20 expression or increased TNFα secretion rate are expected to have elevated NF-κB activity even in the absence of stimulation. This may lead to chronic inflammation and promote cancer due to the persistent activation of antiapoptotic genes induced by NF-κB. There is growing evidence that A20 mutations correlate with several types of lymphomas and elevated TNFα secretion is characteristic of many cancers. Interestingly, A20 loss or dysfunction also leaves the organism vulnerable to septic shock and massive apoptosis triggered by the uncontrolled TNFα secretion, which at high levels overcomes the antiapoptotic action of NF-κB. It is thus tempting to speculate that some cancers of deregulated NF-κB signaling may be prone to the pathogen-induced apoptosis.

TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

Energy Technology Data Exchange (ETDEWEB)

Woods, Dori C., E-mail: dwoods2@partners.org [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)

2011-06-17

Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

Nuclear factor kB (NF-KB): signalosoma and its importance in cancer and inflammatories diseases

International Nuclear Information System (INIS)

Echeverri, Nancy P; Mockus, Ismena S

2008-01-01

The nuclear factor B (NF- B) is a dimer conformed by Rel family. NF- B is found in cytoplasm bound to inhibitor proteins (I B). I B are phosphorylated by different kinases who are part of signalosome as IeB kinases (IKK , IKK and NF- B essential modulator or NEMO), the mitogenic activated protein kinase (MAPK or p38) and NF-eB inducer kinase (NIK). These kinases are activated by different cytokines and ultraviolet light, I B phosphorylated induce their ubiquitination and proteosome degradation subsequently NF- B release and nucleus translocation. Nowadays, the NF- B activation by oxidative stress, genotoxic stress and DNA damage pathways. In contrast with the classical pathway, in this pathway there are a SUMOilation and nuclear translocation of NEMO. In nucleus NEMO interact with ataxia telangiectasia muted which is activated by chromatin changes and DNA damage. The complex ATM/NEMO is later translocated to cytoplasm where IKK is phosphorylated by ATM bringing to ubiquitination and thus NF- B releasing which is translocated to nucleus. NF- B induces survival rising antioxidants enzymes as superoxide dismutase, catalase and glutathione. These enzymes act in the control of oxidative species levels in the cell. NF- B over expression is related with inflammation and cancer. Nowadays, is development a pharmacological search which can act inhibiting NF- B signalosome molecules, not only to inflammatory disease whereas to radiotherapy and chemotherapy cancer resistance.

In silico identification of NF-kappaB-regulated genes in pancreatic beta-cells

Directory of Open Access Journals (Sweden)

Eizirik Decio L

2007-02-01

Full Text Available Abstract Background Pancreatic beta-cells are the target of an autoimmune attack in type 1 diabetes mellitus (T1DM. This is mediated in part by cytokines, such as interleukin (IL-1β and interferon (IFN-γ. These cytokines modify the expression of hundreds of genes, leading to beta-cell dysfunction and death by apoptosis. Several of these cytokine-induced genes are potentially regulated by the IL-1β-activated transcription factor (TF nuclear factor (NF-κB, and previous studies by our group have shown that cytokine-induced NF-κB activation is pro-apoptotic in beta-cells. To identify NF-κB-regulated gene networks in beta-cells we presently used a discriminant analysis-based approach to predict NF-κB responding genes on the basis of putative regulatory elements. Results The performance of linear and quadratic discriminant analysis (LDA, QDA in identifying NF-κB-responding genes was examined on a dataset of 240 positive and negative examples of NF-κB regulation, using stratified cross-validation with an internal leave-one-out cross-validation (LOOCV loop for automated feature selection and noise reduction. LDA performed slightly better than QDA, achieving 61% sensitivity, 91% specificity and 87% positive predictive value, and allowing the identification of 231, 251 and 580 NF-κB putative target genes in insulin-producing INS-1E cells, primary rat beta-cells and human pancreatic islets, respectively. Predicted NF-κB targets had a significant enrichment in genes regulated by cytokines (IL-1β or IL-1β + IFN-γ and double stranded RNA (dsRNA, as compared to genes not regulated by these NF-κB-dependent stimuli. We increased the confidence of the predictions by selecting only evolutionary stable genes, i.e. genes with homologs predicted as NF-κB targets in rat, mouse, human and chimpanzee. Conclusion The present in silico analysis allowed us to identify novel regulatory targets of NF-κB using a supervised classification method based on

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB

Directory of Open Access Journals (Sweden)

Laura D’Ignazio

2017-05-01

Full Text Available Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB. Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk.

The D. melanogaster capa-1 neuropeptide activates renal NF-kB signaling.

Science.gov (United States)

Terhzaz, Selim; Overend, Gayle; Sebastian, Sujith; Dow, Julian A T; Davies, Shireen-A

2014-03-01

The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is critical for fluid homeostasis and has been associated with desiccation tolerance in the fly, Drosophila melanogaster. The mode of capa signaling is highly complex, affecting calcium, nitric oxide and cyclic GMP pathways. Such complex physiological regulation by cell signaling pathways may occur ultimately for optimal organismal stress tolerance to multiple stressors. Here we show that D. melanogaster capa-1 (Drome-capa-1) acts via the Nuclear Factor kappa B (NF-kB) stress signaling network. Human PCR gene arrays of capaR-transfected Human Embryonic Kidney (HEK) 293 cells showed that Drome-capa-1 increases expression of NF-kB, NF-kB regulated genes including IL8, TNF and PTGS2, and NF-kB pathway-associated transcription factors i.e. EGR1, FOS, cJUN. Furthermore, desiccated HEK293 cells show increased EGR1, EGR3 and PTGS2 - but not IL8, expression. CapaR-transfected NF-kB reporter cells showed that Drome-capa-1 increased NF-kB promoter activity via increased calcium. In Malpighian tubules, both Drome-capa-1 stimulation and desiccation result in increased gene expression of the D. melanogaster NF-kB orthologue, Relish; as well as EGR-like stripe and klumpfuss. Drome-capa-1 also induces Relish translocation in tubule principal cells. Targeted knockdown of Relish in only tubule principal cells reduces desiccation stress tolerance of adult flies. Together, these data suggest that Drome-capa-1 acts in desiccation stress tolerance, by activating NF-kB signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor Suppression*

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Liu, Feiyan; Bardhan, Kankana; Yang, Dafeng; Thangaraju, Muthusamy; Ganapathy, Vadivel; Waller, Jennifer L.; Liles, Georgia B.; Lee, Jeffrey R.; Liu, Kebin

2012-01-01

Fas is a member of the death receptor family. Stimulation of Fas leads to induction of apoptotic signals, such as caspase 8 activation, as well as “non-apoptotic” cellular responses, notably NF-κB activation. Convincing experimental data have identified NF-κB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-κB activity. On the other hand, compelling data have also shown that NF-κB activity enhances tumor cell sensitivity to apoptosis and senescence. Furthermore, although stimulation of Fas activates NF-κB, the function of NF-κB in the Fas-mediated apoptosis pathway remains largely undefined. In this study, we observed that deficiency of either Fas or FasL resulted in significantly increased incidence of 3-methylcholanthrene-induced spontaneous sarcoma development in mice. Furthermore, Fas-deficient mice also exhibited significantly greater incidence of azoxymethane and dextran sodium sulfate-induced colon carcinoma. In addition, human colorectal cancer patients with high Fas protein in their tumor cells had a longer time before recurrence occurred. Engagement of Fas with FasL triggered NF-κB activation. Interestingly, canonical NF-κB was found to directly bind to the FAS promoter. Blocking canonical NF-κB activation diminished Fas expression, whereas blocking alternate NF-κB increased Fas expression in human carcinoma cells. Moreover, although canonical NF-κB protected mouse embryo fibroblast (MEF) cells from TNFα-induced apoptosis, knocking out p65 diminished Fas expression in MEF cells, resulting in inhibition of FasL-induced caspase 8 activation and apoptosis. In contrast, knocking out p52 increased Fas expression in MEF cells. Our observations suggest that canonical NF-κB is a Fas transcription activator and alternate NF-κB is a Fas transcription repressor, and Fas functions as a suppressor of spontaneous sarcoma and colon carcinoma. PMID:22669972

NF-kB as a mediator of brain inflammation in AD.

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Hong, Jin Tae

2017-08-07

Alzheimer's disease is the most common form of dementia. It is characterized by beta-amyloid peptide fibrils which are extracellular deposition of a specific protein, and is accompanied by extensive neuroinflammation. Various studies show the presence of a number of inflammation markers in the AD brain: elevated inflammatory cytokines and chemokines, and an accumulation of activated microglia in the damaged regions. NF-kB is a redox of transcriptional factors, and it is known to be located in the genes involved in amyloidogenesis and inflammation. Epidemiological studies have shown that NF-kB is elevated in the AD patient brain, and long-term use of non-steroidal anti-inflammatory drugs suppresses the progression of AD and delays its onset, suggesting that there is a close correlation between NF-kB and AD pathogenesis. This study is (1) to assess the association between NF-kB activity and AD through discussion of a variety of experimental and clinical studies on AD and (2) to review treatment strategies designed to treat or prevent AD with NF-kB inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polycystin-1 promotes PKCα-mediated NF-κB activation in kidney cells

International Nuclear Information System (INIS)

Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky; Mangolini, Alessandra; Pinton, Paolo; Witzgall, Ralph; Rizzuto, Rosario; Senno, Laura del

2006-01-01

Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-κB signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293 CTT ), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-κB nuclear levels and NF-κB-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-κB promoter activation was mediated by PKCα because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293 CTT cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-κB inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKCα-mediated NF-κB signalling and cell survival

Determination of the phosphorylated neurofilament subunit NF-H (pNF-H in cerebro-spinal fluid as biomarker in acute traumatic spinal cord injuries / Dozarea neurofilamentelor fosforilate (subunitatea pNF-H ȋn LCR ca biomarker ȋn traumatismul vertebro-medular acut

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Ungureanu Didona

2014-09-01

Full Text Available Obiectivul studiului. Obiectivul acestui studiu a fost dozarea neurofilamentelor fosforilate (subunitatea pNF-H în lichidul cefalorahidian al pacienţilor cu leziuni traumatice ale măduvei spinării şi stabilirea unei corelaţii intre valoarea pNF-H şi gravitatea leziunilor medulare. Material şi metode. Studiul a inclus 15 pacienţi cu leziuni traumatice acute medulare: opt pacienţi cu leziuni medulare complete şi şapte pacienţi cu leziuni medulare incomplete. Gravitatea leziunilor medulare a fost apreciată folosind scala ASIA (American Spinal Injury Association scale şi la toti pacientii s-a aplicat tratamentul chirurgical în primele 24 de ore (decompresiune medulară şi stabilizare vertebrală. S-a facut determinarea zilnică a pNF-H din LCR folosind testul ELISA specific şi am corelat aceste valori cu evoluţia clinică. Rezultate. Subunitatea pNF-H a fost evidenţiată în LCR la toţi pacienţii cu traumatisme acute vertebro-medulare şi valorile au fost diferite în cazurile leziunilor medulare complete faţa de leziunile incomplete. Nivelul pNF-H din LCR a fost de zece până la o sută de ori mai mare în leziunile medulare complete fata de cazurile cu leziuni incomplete, unde nivelul acestui biomarker a fost aproape normal. Pacienţii cu o evoluţie neurologică favorabilă după tratament au avut un model specific al valorilor zilnice de pNF-H: o creştere bruscă până la o valoare maximă apoi o scădere progresivă până la normal. Valorile maxime au fost diferite în fiecare caz, de 10 ori până la 170 de ori mai mari faţă de normal. Concluzii. Forma fosforilată a subunităţii neurofilamentelor cu greutate moleculară mare pNF-H din lichidul cefalorahidian poate fi un biomarker specific pentru leziunile acute traumatice ale măduvei spinării corelat cu severitatea leziunilor medulare. pNF-H pare a fi un biomarker predictiv deoarece modelul evolutiv al valorilor sale arată reducerea sau blocarea leziunilor

Non-coding RNA ANRIL and the number of plexiform neurofibromas in patients with NF1 microdeletions

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Mußotter Tanja

2012-10-01

Full Text Available Abstract Background Neurofibromatosis type-1 (NF1 is caused by mutations of the NF1 gene at 17q11.2. In 95% of non-founder NF1 patients, NF1 mutations are identifiable by means of a comprehensive mutation analysis. 5-10% of these patients harbour microdeletions encompassing the NF1 gene and its flanking regions. NF1 is characterised by tumours of the peripheral nerve sheaths, the pathognomonic neurofibromas. Considerable inter- and intra-familial variation in expressivity of the disease has been observed which is influenced by genetic modifiers unrelated to the constitutional NF1 mutation. The number of plexiform neurofibromas (PNF in NF1 patients is a highly heritable genetic trait. Recently, SNP rs2151280 located within the non-coding RNA gene ANRIL at 9p21.3, was identified as being strongly associated with PNF number in a family-based association study. The T-allele of rs2151280, which correlates with reduced ANRIL expression, appears to be associated with higher PNF number. ANRIL directly binds to the SUZ12 protein, an essential component of polycomb repressive complex 2, and is required for SUZ12 occupancy of the CDKN2A/CDKN2B tumour suppressor genes as well as for their epigenetic silencing. Methods Here, we explored a potential association of PNF number and PNF volume with SNP rs2151280 in 29 patients with constitutional NF1 microdeletions using the exact Cochran-Armitage test for trends and the exact Mann–Whitney–Wilcoxon test. Both the PNF number and total tumour volume in these 29 NF1 patients were assessed by whole-body MRI. The NF1 microdeletions observed in these 29 patients encompassed the NF1 gene as well as its flanking regions, including the SUZ12 gene. Results In the 29 microdeletion patients investigated, neither the PNF number nor PNF volume was found to be associated with the T-allele of rs2151280. Conclusion Our findings imply that, at least in patients with NF1 microdeletions, PNF susceptibility is not associated with

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner

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Fitzpatrick, Susan F.; Fábián, Zsolt; Schaible, Bettina; Lenihan, Colin R.; Schwarzl, Thomas [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Rodriguez, Javier [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Zheng, Xingnan; Li, Zongwei [Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Tambuwala, Murtaza M. [School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland (United Kingdom); Higgins, Desmond G.; O' Meara, Yvonne [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Slattery, Craig [School of Biomolecular and Biomedical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Manresa, Mario C. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Fraisl, Peter; Bruning, Ulrike [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Baes, Myriam [Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven (Belgium); Carmeliet, Peter; Doherty, Glen [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Kriegsheim, Alex von [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Cummins, Eoin P. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); and others

2016-06-03

Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1{sup −/−} hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease. -- Highlights: •Genetic ablation of PHD1 upregulates NF-kappaB (NF-κB) in hepatocytes. •Activation of NF-κB leads to differential DNA-binding of p50/p65 and results in differential regulation of apoptotic genes. •We identified proline 191 in the beta subunit of the I-kappaB kinase as a target for PHD1-mediated hydroxylation. •Blockade of prolyl-4-hydroxylases has been found cytoprotective in liver cells.

An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters.

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Giacomo Donati

Full Text Available BACKGROUND: Histone tails have a plethora of different post-translational modifications, which are located differently in "open" and "closed" parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure. PRINCIPAL FINDINGS: We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3. CONCLUSIONS: Two relevant findings are reported: (i NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes.

Biscoito integral: fonte de fibra, isento de lactose e gordura trans. = Integral cookie: fiber source, free of lactose and trans fats.

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Meire Ferrari de Castro

2008-12-01

Full Text Available A demanda por produtos isentos de lactose, gordura trans e rico em fi bra é crescente no mercado alimentício. O presente estudo de natureza transversal, com coleta de dados primários, teve como objetivo desenvolver um tipo de biscoito rico em fibras, isento de lactose e livre de gorduras trans. Os biscoitos foram submetidos à avaliação sensorial com 144 consumidores, freqüentadores de uma panifi cadora de Maringá, Paraná, sendo 61% (n = 88 sexo femininoe 39% (n = 56 do sexo masculino, na faixa etária de 15 a 80 anos de idades. Para o teste de aceitação do produto, utilizou-se a escala hedônica de nove pontos (1 a 9 e a intenção de compra do produto com uma escala de cinco pontos. Participaram da pesquisa 144 pessoas que relataram 59% de aceitação de 8 a 9 pontos na escala hedônica. Somente 1% desgostaram, em diferentes níveis, dos biscoitos produzidos. Para a intenção de compra, 79% dos julgadores apresentaram-se propensos a compra do produto. Em 21% dos casos, os julgadores ou estariam em dúvida (15% ou defi nitivamente não comprariam o produto (6%. O produto final apresentou quantidades satisfatórias de fibras, ficando insento de lactose e gordura trans. = The demand for products free of lactose, trans fats and high in fiber is increasing in the food market. The present study of transverse nature, with primary data collect, aimed to develop a type of cookie rich in fibers, exempt of lactos, free from trans fats. The cookies were submitted to sensory evaluation with 144 consumers, who attend a bakery in Maringá of Paraná State - Brazil, 61% (n = 88 female and 39% (n = 56 male, aged 15-80 years ages. For the test of acceptance of the product, been used the hedonic scale of nine points (1 to 9, and the intention of purchase of the product with a scale of fivepoints. Hundred and forty four people have participated in the research that told as acceptance from 8 to 9 points in the scale of 59%. Only 1% disgusted et

Late-phase synthesis of I��B�� insulates the TLR4-activated canonical NF-��B pathway from noncanonical NF-��B signaling in macrophages

OpenAIRE

Chatterjee, Budhaditya; Banoth, Balaji; Mukherjee, Tapas; Taye, Nandaraj; Vijayaragavan, Bharath; Chattopadhyay, Samit; Gomes, James; Basak, Soumen

2016-01-01

The nuclear factor ��B (NF-��B) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-��B signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of ��B�� (I��B��). The noncanonical NF-��B pathway is required for the differentiation of immune cells; however, crosstalk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from ...

Classical NF-κB Metabolically Reprograms Sarcoma Cells Through Regulation of Hexokinase 2

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Priya Londhe

2018-04-01

Full Text Available BackgroundMetabolic reprogramming has emerged as a cancer hallmark, and one of the well-known cancer-associated metabolic alterations is the increase in the rate of glycolysis. Recent reports have shown that both the classical and alternative signaling pathways of nuclear factor κB (NF-κB play important roles in controlling the metabolic profiles of normal cells and cancer cells. However, how these signaling pathways affect the metabolism of sarcomas, specifically rhabdomyosarcoma (RMS and osteosarcoma (OS, has not been characterized.MethodsClassical NF-κB activity was inhibited through overexpression of the IκBα super repressor of NF-κB in RMS and OS cells. Global gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0, and data were interpreted using gene set enrichment analysis. Seahorse Bioscience XFe24 was used to analyze oxygen consumption rate as a measure of aerobic respiration.ResultsInhibition of classical NF-κB activity in sarcoma cell lines restored alternative signaling as well as an increased oxidative respiratory metabolic phenotype in vitro. In addition, microarray analysis indicated that inhibition of NF-κB in sarcoma cells reduced glycolysis. We showed that a glycolytic gene, hexokinase (HK 2, is a direct NF-κB transcriptional target. Knockdown of HK2 shifted the metabolic profile in sarcoma cells away from aerobic glycolysis, and re-expression of HK2 rescued the metabolic shift induced by inhibition of NF-κB activity in OS cells.ConclusionThese findings suggest that classical signaling of NF-κB plays a crucial role in the metabolic profile of pediatric sarcomas potentially through the regulation of HK2.

The Effects of Treatments on Batu Banana Flour and Percentage of Wheat Substitution on The Resistant Starch, In Vitro Starch Digestibility Content and Palatability of Cookies Made with Banana (Musa balbisiana Colla) Flour

Science.gov (United States)

Ratnasari, D.; Rustanti, N.; Arifan, F.; Afifah, DN

2018-02-01

Diabetes mellitus (DM) is the most common endocrine disease worldwide. Resistant starch is polysaccharide that is recommended for DM patient diets. One of the staple crops containing resistant starch is banana. It is the fourth most important staple crop in the world and critical for food security, best suited plant in warm, frost-free, and coastal climates area. Among banana varieties, Batu bananas (Musa balbisiana Colla) had the highest content of resistant starch (~39%), but its use as a food ingredient is limited. Inclusion of Batu banana flour into cookies manufacturing would both increase the economic value of Batu bananas and provide alternative snacks for DM patients. Here we sought to examine whether cookies made with modified Batu banana flour would be a suitable snack for DM patients. This study used a completely randomized design with two factors: substitution of Batu banana flour (25%, 50%,75%) for wheat-based flour and Batu banana flour treatment methods (no treatment, autoclaving-cooling, autoclaving-cooling-spontaneous fermentation). The resistant starch and in vitro starch digestibility levels were analyzed using two-way ANOVA and Tukey test, whereas the acceptance level was analyzed by Friedman and Wilcoxon tests. The content of resistant starch and in vitro starch digestibility of the different treatments ranged from 3.10 to 15.79% and 16.03 to 52.59%, respectively. Both factors differed significantly (p0.05). Meanwhile, palatability in terms of color, aroma, texture, and flavor differed significantly among the different treatments and starch contents (ppatients. Keywords: Batu banana, cookies, resistant starch, in vitro starch digestibility

Mycobacterium leprae induces NF-κB-dependent transcription repression in human Schwann cells

International Nuclear Information System (INIS)

Pereira, Renata M.S.; Calegari-Silva, Teresa Cristina; Hernandez, Maristela O.; Saliba, Alessandra M.; Redner, Paulo; Pessolani, Maria Cristina V.; Sarno, Euzenir N.; Sampaio, Elizabeth P.; Lopes, Ulisses G.

2005-01-01

Mycobacterium leprae, the causative agent of leprosy, invades peripheral nerve Schwann cells, resulting in deformities associated with this disease. NF-κB is an important transcription factor involved in the regulation of host immune antimicrobial responses. We aimed in this work to investigate NF-κB signaling pathways in the human ST88-14 Schwannoma cell line infected with M. leprae. Gel shift and supershift assays indicate that two NF-κB dimers, p65/p50 and p50/p50, translocate to the nucleus in Schwann cells treated with lethally irradiated M. leprae. Consistent with p65/p50 and p50/p50 activation, we observed IκB-α degradation and reduction of p105 levels. The nuclear translocation of p50/p50 complex due to M. leprae treatment correlated with repression of NF-κB-driven transcription induced by TNF-α. Moreover, thalidomide inhibited p50 homodimer nuclear translocation induced by M. leprae and consequently rescues Schwann cells from NF-κB-dependent transcriptional repression. Here, we report for the first time that M. leprae induces NF-κB activation in Schwann cells and thalidomide is able to modulate this activation

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

Science.gov (United States)

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

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Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

International Nuclear Information System (INIS)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming

2016-01-01

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells

Energy Technology Data Exchange (ETDEWEB)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-ming, E-mail: zengshenming@gmail.com

2016-04-22

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.

ESTUDO TEÓRICO DAS PROPRIEDADES CINÉTICAS DA REAÇÃO NF+F = N+F2

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Danielle Maria Fernandes do Prado

2010-08-01

Full Text Available O principal objetivo dos estudos com o Trifluoreto de nitrogênio é estudar a dissociação deste em nitrogênio e flúor. Para o entendimento e a determinação do correto caminho de dissociação do NF3, é necessário estudar uma série de reações elementares, como passo intermediário para alcançar a reação global deste sistema. Neste projeto é apresentado uma proposta de determinação das propriedades cinéticas e dinâmicas das reações envolvidas nos mecanismos de dissociação do NF3 . Para a realização deste estudo será empregada a Teoria das Estruturas de Transição (TST, juntamente com as correções de tunelamento, de Wigner e Eckart.

Copine-I: Modulator of NF-kappa B Transcription and Prostate Cancer Survival

National Research Council Canada - National Science Library

Mayo, Marty W; Creutz, Carl

2008-01-01

The purpose of our studies is to elucidate how Copine-I antagonizes NF-.B transcription. Nuclear factor-.B (NF-.B) is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression...

Molecular imaging of the transcription factor NF-κB, a primary regulator of stress response

International Nuclear Information System (INIS)

Carlsen, Harald; Alexander, George; Austenaa, Liv M.I.; Ebihara, Kanae; Blomhoff, Rune

2004-01-01

A wide range of environmental stress and human disorders involves inappropriate regulation of NF-κB, including cancers and numerous inflammatory conditions. We have developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time non-invasive imaging of NF-κB activity in intact animals. We show that, in the absence of stimulation, strong, intrinsic luminescence is evident in lymph nodes in the neck region, thymus, and Peyer's patches. Treating mice with stressors, such as TNF-α, IL-1α, or lipopolysaccharide (LPS) increases the luminescence in a tissue-specific manner, with the strongest activity observable in the skin, lungs, spleen, Peyer's patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue exhibit less intense activities. Exposure of the skin to a low dose of UV-B radiation increases luminescence in the exposed areas. In ocular experiments, LPS- and TNF-α injected NF-κB-luciferase transgenic mice exhibit a 20-40-fold increase in lens NF-κB activity, similar to other LPS- and TNF-α-responsive organs. Peak NF-κB activity occurs 6 h after injection of TNF-α and 12 h after injection of LPS. Peak activities occur, respectively, 3 and 6 h later than that in other tissues. Mice exposed to 360 J/m 2 of UV-B exhibit a 16-fold increase in NF-κB activity 6 h after exposure, characteristically similar to TNF-α-exposed mice. Thus, in NF-κB-luciferase transgenic mice, NF-κB activity also occurs in lens epithelial tissue and is activated when the intact mouse is exposed to classical stressors. Furthermore, as revealed by real-time non-invasive imaging, induction of chronic inflammation resembling rheumatoid arthritis produces strong NF-κB activity in the affected joints. Finally, we have used the model to demonstrate NF-κB regulation by manipulating the Vitamin A status in mice. NF-κB activity is elevated in mice fed a Vitamin A deficient (VAD) diet, and suppressed by surplus doses of

Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

Science.gov (United States)

Baud, Véronique; Karin, Michael

2009-01-01

Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

NF-PRO research on a repository for vitrified waste and spent fuel

International Nuclear Information System (INIS)

Sneyers, A.

2006-01-01

NF-PRO is a four-year (2004-2007) Integrated Project supported by funding under the Sixth Research (EURATOM) Programme of the European Commission. NF-PRO is coordinated by SCK C EN and investigates key processes in the near-field of geological repositories for the disposal of high-level vitrified waste and spent nuclear fuel. The near-field of a geological repository consists of the area surrounding the waste packages and is composed of several engineered barriers that enclose and confine the disposed waste. These barriers include the waste form, the waste canisters, backfills, seals, plugs and the part of the host rock that has been modified by the excavation of the repository. In all repository designs under investigation within EU Member States, the near-field plays an important role in ensuring the overall safety of disposal: its principal function is to retain radionuclides over extended periods of time and to minimise their release from the waste to the host rock. The main objective of NF-PRO is to integrate European research on the near field with the aim of enhancing common understanding of the long-term changes taking place in a deep repository. NF-PRO assesses how these changes affect the containment of the disposed radioactive waste. Knowledge generated by the project can be applied in waste management programmes to optimise repository designs and to make barriers functional and resource-efficient. The integration of results from detailed process studies in assessments on the overall near-field system performance is a key objective of NF-PRO. The level of integration envisaged by NF-PRO has not yet been achieved in earlier research projects supported by the European Commission. Accordingly, NF PRO represents a major step forward in the establishing of the scientific and technical basis for geological disposal and the safe management of radioactive wastes

Memory extinction entails the inhibition of the transcription factor NF-kappaB.

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Emiliano Merlo

Full Text Available In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed. The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response. The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. Here we studied the participation of a transcription factor, NF-kappaB, in memory extinction. In the crab context-signal memory, the activation of NF-kappaB plays a critical role in consolidation and reconsolidation, memory processes that are well characterized in this model. The administration of a NF-kappaB inhibitor, sulfasalazine prior to extinction session impeded spontaneous recovery. Moreover, reinstatement experiments showed that the original memory was not affected and that NF-kappaB inhibition by sulfasalazine impaired spontaneous recovery strengthening the ongoing memory extinction process. Interestingly, in animals with fully consolidated memory, a brief re-exposure to the training context induced neuronal NF-kappaB activation and reconsolidation, while prolonged re-exposure induced NF-kappaB inhibition and memory extinction. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction. Moreover, we propose the inhibition of NF-kappaB as the engaged mechanism underlying extinction, supporting a novel approach for the pharmacological enhancement of this memory process. The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies

NF-κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression

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Rob J. A. Verhoeven

2018-04-01

Full Text Available Epstein–Barr virus (EBV nuclear antigen 1 (EBNA1 is one of the few viral proteins expressed by EBV in nasopharyngeal carcinoma (NPC, most likely because of its essential role in maintaining the viral genome in EBV-infected cells. In NPC, EBNA1 expression is driven by the BamHI-Q promoter (Qp, which is regulated by both cellular and viral factors. We previously determined that the expression of another group of EBV transcripts, BamHI-A rightward transcripts (BARTs, is associated with constitutively activated nuclear factor-κB (NF-κB signaling in NPC cells. Here, we show that, like the EBV BART promoter, the EBV Qp also responds to NF-κB signaling. NF-κB p65, but not p50, can activate Qp in vitro, and NF-κB signaling regulates Qp-EBNA1 expression in NPC cells, as well as in other EBV-infected epithelial cells. The introduction of mutations in the putative NF-κB site reduced Qp activation by the NF-κB p65 subunit. Binding of p65 to Qp was shown by chromatin immunoprecipitation (ChIP analysis, while electrophoretic mobility shift assays (EMSAs demonstrated that p50 can also bind to Qp. Inhibition of NF-κB signaling by the IκB kinase inhibitor PS-1145 resulted in the downregulation of Qp-EBNA1 expression in C666-1 NPC cells. Since EBNA1 has been reported to block p65 activation by inhibiting IKKα/β through an unknown mechanism, we suggest that, in NPC, NF-κB signaling and EBNA1 may form a regulatory loop which supports EBV latent gene expression, while also limiting NF-κB activity. These findings emphasize the role of NF-κB signaling in the regulation of EBV latency in EBV-associated tumors.

Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

International Nuclear Information System (INIS)

Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.; Rattray, Marcus

2012-01-01

Highlights: ► We tested the hypothesis that low concentrations of flavonoids inhibit NF-κB in astrocytes. ► Primary cultured astrocytes possess a functional κB-system, measured using luciferase assays. ► Seven flavonoids (100 nM–1 μM) failed to reduce NF-κB activity in astrocytes. ► Four flavonoids (100 nM–1 μM) failed to reduce TNFa-stimulated NF-κB activity in astrocytes. ► (−)-Epicatechin did not regulate nuclear translocation of the NF-κB subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((−)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

Methylation-Dependent Activation of CDX1 through NF-κB

Science.gov (United States)

Rau, Tilman T.; Rogler, Anja; Frischauf, Myrjam; Jung, Andreas; Konturek, Peter C.; Dimmler, Arno; Faller, Gerhard; Sehnert, Bettina; El-Rifai, Wael; Hartmann, Arndt; Voll, Reinhard E.; Schneider-Stock, Regine

2013-01-01

The caudal homeobox factor 1 (CDX1) is an essential transcription factor for intestinal differentiation. Its aberrant expression in intestinal metaplasia of the upper gastrointestinal tract is a hallmark within the gastritis-metaplasia-carcinoma sequence. CDX1 expression is influenced by certain pathways, such as Wnt, Ras, or NF-κB signaling; however, these pathways alone cannot explain the transient expression of CDX1 in intestinal metaplasia or the molecular inactivation mechanism of its loss in cases of advanced gastric cancer. In this study, we investigated the epigenetic inactivation of CDX1 by promoter methylation, as well as the functional link of CDX1 promoter methylation to the inflammatory NF-κB signaling pathway. We identified methylation-dependent NF-κB binding to the CDX1 promoter and quantified it using competitive electrophoretic mobility shift assays and chromatin immunoprecipitation. A methylated CDX1 promoter was associated with closed chromatin structure, reduced NF-κB binding, and transcriptional silencing. Along the gastritis-metaplasia-carcinoma sequence, we observed a biphasic pattern of tumor necrosis factor-α (TNF-α) protein expression and an inverse biphasic pattern of CDX1 promoter methylation; both are highly consistent with CDX1 protein expression. The stages of hyper-, hypo-, and hyper-methylation patterns of the CDX1 promoter were inversely correlated with the NF-κB signaling activity along this sequence. In conclusion, these functionally interacting events drive CDX1 expression and contribute to intestinal metaplasia, epithelial dedifferentiation, and carcinogenesis in the human stomach. PMID:22749770

Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

Science.gov (United States)

Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

2013-01-01

The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice.

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Brian Poligone

Full Text Available BACKGROUND: Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin. METHODS: A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice with increased NF-κB activity. RESULTS: The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata. CONCLUSION: Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.

Diisononyl phthalate aggravates allergic dermatitis by activation of NF-kB.

Science.gov (United States)

Kang, Jun; Song, Jing; Shen, Shiping; Li, Baizhan; Yang, Xu; Chen, Mingqing

2016-12-20

Several epidemiological studies have suggested a possible link between exposure to Diisononyl phthalate (DINP) and the development of allergies. These findings remain controversial since there is insufficient scientific evidence to assess the ability of DINP to influence allergic immune responses. In addition, the mechanisms behind DINP-caused allergic diseases have not been fully elucidated. In this study, Balb/c mice were orally exposed to DINP for 3 weeks and were then sensitized with fluorescein isothiocyanate (FITC). We showed that oral exposure to DINP could aggravate allergic-dermatitis-like lesions, indicated by an increase in the number of mast cells, and in increased skin edema in FITC-induced contact hypersensitivity. This deterioration was concomitant with increased total serum immunoglobulin-E and Th2 cytokines. We determined the oxidative damage and the activation of nuclear factor-kb (NF-kB). The data demonstrated that DINP could promote oxidative damage and the activation of NF-kB in the skin. The expression of thymic stromal lymphopoietin and the activation of signal transducer and activator of transcriptions 3, 5 and 6 were enhanced concomitant with exacerbated allergic dermatitis effects and the activation of NF-kB induced by DINP. These effects were alleviated by pyrollidine dithiocarbamate, an inhibitor of NF-kB. The results suggest that oral exposure to DINP aggravated allergic contact dermatitis, which was positively regulated via NF-kB.

NiO-NF/MWCNT nanocomposite catalyst as a counter electrode for high performance dye-sensitized solar cells

International Nuclear Information System (INIS)

Raissan Al-bahrani, Majid; Liu, Linfeng; Ahmad, Waqar; Tao, Jiayou; Tu, Fanfan; Cheng, Ze; Gao, Yihua

2015-01-01

Highlights: • High-performance NiO-NF/MWCNT CE was incorporated in a Pt-CE in DSSCs. • NiO-NF/MWCNT CE exhibits a high power conversion efficiency (PCE) of 7.63%. • NiO-NF/MWCNT composite has a high catalytic activity for the reduction of I 3 − . • NiO-NF/MWCNT composite has a low R ct on the electrolyte/CE interface. - Abstract: In this paper, we fabricated nickel oxide nanofilament/multiwall carbon nanotubes (NiO-NF/MWCNT) nanocomposite by a simple hydrothermal synthesis method as a counter- electrode (CE) in a dye-sensitized solar cell (DSSC). Transmission electron microscopy, scanning electron microscopy images and X-ray diffraction analysis clearly indicated the formation of NiO-NF/MWCNT nanocomposite. The electro-chemical properties of NiO-NF/MWCNT CE are studied by cyclic voltammetry and electrochemical impedance spectroscopy. In particular, current-voltage measurements indicated superior power conversion efficiency (PCE) of 7.63% of the NiO-NF/MWCNT CE compared to 6.72% for the platinum (Pt). The superior photovoltaic performance and low cost of the NiO-NF/MWCNT nanocomposite can be potentially exploited as a new counter-electrode in DSSCs

Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

Directory of Open Access Journals (Sweden)

Man Lyang Kim

Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

BFV activates the NF-κB pathway through its transactivator (BTas) to enhance viral transcription

International Nuclear Information System (INIS)

Wang Jian; Tan Juan; Zhang Xihui; Guo Hongyan; Zhang Qicheng; Guo Tingting; Geng Yunqi; Qiao Wentao

2010-01-01

Multiple families of viruses have evolved sophisticated strategies to regulate nuclear factor-κB (NF-κB) signaling, which plays a pivotal role in diverse cellular events, including virus-host interactions. In this study, we report that bovine foamy virus (BFV) is able to activate the NF-κB pathway through the action of its transactivator, BTas. Both cellular IKKβ and IκBα also participate in this activation. In addition, we demonstrate that BTas induces the processing of p100, which implies that BTas can activate NF-κB through a noncanonical pathway as well. Co-immunoprecipitation analysis shows that BTas interacts with IKK catalytic subunits (IKKα and IKKβ), which may be responsible for regulation of IKK kinase activity and persistent NF-κB activation. Furthermore, our results indicate that the level of BTas-mediated LTR transcription correlates with the activity of cellular NF-κB. Together, this study suggests that BFV activates the NF-κB pathway through BTas to enhance viral transcription.

Pedilanthus tithymaloides Inhibits HSV Infection by Modulating NF-κB Signaling.

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Durbadal Ojha

Full Text Available Pedilanthus tithymaloides (PT, a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2. Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 μg/ml, respectively, with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/ml, respectively. The inhibitory effect was significant (p<0.001 when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-2-infected cells with extract or luteolin suppressed NF-κB activation. Although NF-κB, JNK and MAPK activation was compromised during HSV replication, neither the extract nor luteolin affected HSV-2-induced JNK1/2 and MAPK activation. Moreover, the PT leaf extract and luteolin potently down-regulated the expression of tumor necrosis factor (TNF-α, Interleukin (IL-1β, IL-6, NO and iNOS and the production of gamma interferon (IFN-γ, which are directly involved in controlling the NF-κB signaling pathway. Thus, our results indicate that both PT leaf extract and luteolin modulate the NF-κB signaling pathway, resulting in the inhibition of HSV-2 replication.

Measurement of electric fields in the H-1NF heliac

International Nuclear Information System (INIS)

James, B.W.; Howard, J.

1999-01-01

There are a number of laser induced fluorescence techniques which can be used to measure internal plasma electric fields. It is planned to use a technique based on Stark mixing of energy levels in a supersonic beam containing metastable helium atoms to measure radial electric fields in H-1NF. Enhanced values of radial electric field are associated with improved confinement modes in H-1NF and other magnetically confined plasmas

The oncoprotein gankyrin interacts with RelA and suppresses NF-κB activity

International Nuclear Information System (INIS)

Higashitsuji, Hiroaki; Higashitsuji, Hisako; Liu, Yu; Masuda, Tomoko; Fujita, Takanori; Abdel-Aziz, H. Ismail; Kongkham, Supranee; Dawson, Simon; John Mayer, R.; Itoh, Yoshito; Sakurai, Toshiharu; Itoh, Katsuhiko; Fujita, Jun

2007-01-01

Gankyrin is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It interacts with multiple proteins and accelerates degradation of tumor suppressors Rb and p53. Since gankyrin consists of 7 ankyrin repeats and is structurally similar to IκBs, we investigated its interaction with NF-κB. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFα-induced transcriptional activity of NF-κB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-κB DNA-binding activity or nuclear translocation of RelA induced by TNFα in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-κB activity, which was further suppressed by gankyrin. The inhibitory effect of gankyrin was abrogated by nicotinamide as well as down-regulation of SIRT1, a class III histone deacetylase. Thus, gankyrin binds to NF-κB and suppresses its activity at the transcription level by modulating acetylation via SIRT1

Injury Signals Cooperate with Nf1 Loss to Relieve the Tumor-Suppressive Environment of Adult Peripheral Nerve

Directory of Open Access Journals (Sweden)

Sara Ribeiro

2013-10-01

Full Text Available Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1−/− mSCs redifferentiate normally, whereas at the wound site Nf1−/− mSCs give rise to neurofibromas in both Nf1+/+ and Nf1+/− backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.

Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

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Elisabeth Lippert

2009-10-01

Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

Fouling characteristics and cleaning strategies of NF membranes for the advanced treatment of antibiotic production wastewater.

Science.gov (United States)

Wang, Jianxing; Li, Kun; Yu, Dawei; Zhang, Junya; Wei, Yuansong

2017-04-01

The nanofiltration (NF) membrane fouling characteristics and cleaning strategies were investigated through a laboratory-scale NF fouling test treating membrane bioreactor (MBR) effluent and MBR-granular activated carbon (GAC) effluent of an antibiotic production wastewater by DK and NF90 membranes, respectively. Results showed that organic fouling is the main NF membrane fouling for treating both the MBR effluent and MBR-GAC effluent. Soluble microbial by-product (SMP)-like and aromatic protein-like substances were the dominant components in the foulants, whereas humic-like substances had little contribution to the NF fouling. The fouling of DK was more severe than that of NF90. However, foulants respond by UV 254 were more easily to foul NF90 membrane. It could get satisfactory effect using combined cleaning of acid (HCl, pH 2.0∼2.5) and alkali (NaOH + 0.3 wt% NaDS, pH 10.0∼10.5). The favorable cleaning strategy is "acid + alkali" for treating MBR-GAC effluent, while it is "alkali + acid" for treating MBR effluent.

NiO-NF/MWCNT nanocomposite catalyst as a counter electrode for high performance dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Raissan Al-bahrani, Majid [Center for Nanoscale Characterization & Devices (CNCD), Wuhan National Laboratory for Optoelectronics (WNLO)-School of Physics, Huazhong University of Science and Technology - HUST, Luoyu Road 1037, Wuhan 430074 (China); Faculty of Science, Thi-Qar University, Nassiriya (Iraq); Liu, Linfeng [Michael Grätzel Center for Mesoscopic Solar Cells, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074 (China); Ahmad, Waqar; Tao, Jiayou; Tu, Fanfan [Center for Nanoscale Characterization & Devices (CNCD), Wuhan National Laboratory for Optoelectronics (WNLO)-School of Physics, Huazhong University of Science and Technology - HUST, Luoyu Road 1037, Wuhan 430074 (China); Cheng, Ze [School of Physics, Huazhong University of Science and Technology (HUST), Luoyu Road 1037, Wuhan 430074 (China); Gao, Yihua, E-mail: gaoyihua@hust.edu.cn [Center for Nanoscale Characterization & Devices (CNCD), Wuhan National Laboratory for Optoelectronics (WNLO)-School of Physics, Huazhong University of Science and Technology - HUST, Luoyu Road 1037, Wuhan 430074 (China)

2015-03-15

Highlights: • High-performance NiO-NF/MWCNT CE was incorporated in a Pt-CE in DSSCs. • NiO-NF/MWCNT CE exhibits a high power conversion efficiency (PCE) of 7.63%. • NiO-NF/MWCNT composite has a high catalytic activity for the reduction of I{sub 3}{sup −}. • NiO-NF/MWCNT composite has a low R{sub ct} on the electrolyte/CE interface. - Abstract: In this paper, we fabricated nickel oxide nanofilament/multiwall carbon nanotubes (NiO-NF/MWCNT) nanocomposite by a simple hydrothermal synthesis method as a counter- electrode (CE) in a dye-sensitized solar cell (DSSC). Transmission electron microscopy, scanning electron microscopy images and X-ray diffraction analysis clearly indicated the formation of NiO-NF/MWCNT nanocomposite. The electro-chemical properties of NiO-NF/MWCNT CE are studied by cyclic voltammetry and electrochemical impedance spectroscopy. In particular, current-voltage measurements indicated superior power conversion efficiency (PCE) of 7.63% of the NiO-NF/MWCNT CE compared to 6.72% for the platinum (Pt). The superior photovoltaic performance and low cost of the NiO-NF/MWCNT nanocomposite can be potentially exploited as a new counter-electrode in DSSCs.

NF-κB and androgen receptor variant expression correlate with human BPH progression.

Science.gov (United States)

Austin, David C; Strand, Douglas W; Love, Harold L; Franco, Omar E; Jang, Alex; Grabowska, Magdalena M; Miller, Nicole L; Hameed, Omar; Clark, Peter E; Fowke, Jay H; Matusik, Robert J; Jin, Ren J; Hayward, Simon W

2016-04-01

Benign prostatic hyperplasia (BPH) is a common, chronic progressive disease. Inflammation is associated with prostatic enlargement and resistance to 5α-reductase inhibitor (5ARI) therapy. Activation of the nuclear factor-kappa B (NF-κB) pathway is linked to both inflammation and ligand-independent prostate cancer progression. NF-κB activation and androgen receptor variant (AR-V) expression were quantified in transition zone tissue samples from patients with a wide range of AUASS from incidental BPH in patients treated for low grade, localized peripheral zone prostate cancer to advanced disease requiring surgical intervention. To further investigate these pathways, human prostatic stromal and epithelial cell lines were transduced with constitutively active or kinase dead forms of IKK2 to regulate canonical NF-κB activity. The effects on AR full length (AR-FL) and androgen-independent AR-V expression as well as cellular growth and differentiation were assessed. Canonical NF-κB signaling was found to be upregulated in late versus early stage BPH, and to be strongly associated with non-insulin dependent diabetes mellitus. Elevated expression of AR-variant 7 (AR-V7), but not other AR variants, was found in advanced BPH samples. Expression of AR-V7 significantly correlated with the patient AUASS and TRUS volume. Forced activation of canonical NF-κB in human prostatic epithelial and stromal cells resulted in elevated expression of both AR-FL and AR-V7, with concomitant ligand-independent activation of AR reporters. Activation of NF-κB and over expression of AR-V7 in human prostatic epithelial cells maintained cell viability in the face of 5ARI treatment. Activation of NF-κB and AR-V7 in the prostate is associated with increased disease severity. AR-V7 expression is inducible in human prostate cells by forced activation of NF-κB resulting in resistance to 5ARI treatment, suggesting a potential mechanism by which patients may become resistant to 5ARI therapy. �

NF-κB regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes.

Science.gov (United States)

Volcic, Meta; Karl, Sabine; Baumann, Bernd; Salles, Daniela; Daniel, Peter; Fulda, Simone; Wiesmüller, Lisa

2012-01-01

NF-κB is involved in immune responses, inflammation, oncogenesis, cell proliferation and apoptosis. Even though NF-κB can be activated by DNA damage via Ataxia telangiectasia-mutated (ATM) signalling, little was known about an involvement in DNA repair. In this work, we dissected distinct DNA double-strand break (DSB) repair mechanisms revealing a stimulatory role of NF-κB in homologous recombination (HR). This effect was independent of chromatin context, cell cycle distribution or cross-talk with p53. It was not mediated by the transcriptional NF-κB targets Bcl2, BAX or Ku70, known for their dual roles in apoptosis and DSB repair. A contribution by Bcl-xL was abrogated when caspases were inhibited. Notably, HR induction by NF-κB required the targets ATM and BRCA2. Additionally, we provide evidence that NF-κB interacts with CtIP-BRCA1 complexes and promotes BRCA1 stabilization, and thereby contributes to HR induction. Immunofluorescence analysis revealed accelerated formation of replication protein A (RPA) and Rad51 foci upon NF-κB activation indicating HR stimulation through DSB resection by the interacting CtIP-BRCA1 complex and Rad51 filament formation. Taken together, these results define multiple NF-κB-dependent mechanisms regulating HR induction, and thereby providing a novel intriguing explanation for both NF-κB-mediated resistance to chemo- and radiotherapies as well as for the sensitization by pharmaceutical intervention of NF-κB activation.

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

Science.gov (United States)

Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

2012-03-01

The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

Energy Technology Data Exchange (ETDEWEB)

Spilsbury, Alison [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom); Vauzour, David; Spencer, Jeremy P.E. [Molecular Nutrition Group, Centre for Integrative Neuroscience and Neurodynamics, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom); Rattray, Marcus, E-mail: m.a.n.rattray@reading.ac.uk [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)

2012-02-17

Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I

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Kairong Li

2016-07-01

Full Text Available Neurofibromatosis type 1 (NF1 is a common genetic disorder characterized by the occurrence of nerve sheath tumors and considerable clinical heterogeneity. Some translational studies have been limited by the lack of animal models available for assessing patient-specific mutations. In order to test therapeutic approaches that might restore function to the mutated gene or gene product, we developed mice harboring NF1 patient-specific mutations including a nonsense mutation (c.2041C>T; p.Arg681* and a missense mutation (c.2542G>C; p.Gly848Arg. The latter is associated with the development of multiple plexiform neurofibromas along spinal nerve roots. We demonstrate that the human nonsense NF1Arg681* and missense NF1Gly848Arg mutations have different effects on neurofibromin expression in the mouse and each recapitulates unique aspects of the NF1 phenotype, depending upon the genetic context when assessed in the homozygous state or when paired with a conditional knockout allele. Whereas the missense Nf1Gly848Arg mutation fails to produce an overt phenotype in the mouse, animals homozygous for the nonsense Nf1Arg681* mutation are not viable. Mice with one Nf1Arg681* allele in combination with a conditional floxed Nf1 allele and the DhhCre transgene (Nf14F/Arg681*; DhhCre display disorganized nonmyelinating axons and neurofibromas along the spinal column, which leads to compression of the spinal cord and paralysis. This model will be valuable for preclinical testing of novel nonsense suppression therapies using drugs to target in-frame point mutations that create premature termination codons in individuals with NF1.

Targeting of NF-κB to Dendritic Spines Is Required for Synaptic Signaling and Spine Development.

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Dresselhaus, Erica C; Boersma, Matthew C H; Meffert, Mollie K

2018-04-25

Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor κB (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine enrichment (p65ΔSE) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or p65ΔSE both rescue NF-κB-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-κB are selectively impaired in NF-κB-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-κB-dependent growth of dendritic spines to test physiological function of spine-enriched NF-κB in an activity-dependent response. Expression of wild-type p65, but not p65ΔSE, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-κB transcription factor in synaptic activity-dependent responses. SIGNIFICANCE STATEMENT Extensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus specificity to gene regulation, ensuring biologically appropriate responses, remain incompletely understood. NF-κB is a potent transcription factor with evolutionarily conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-κB is localized in both synapse and

NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

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Kisseleva, Tatiana; Song, Li; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian

2006-01-01

The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress. PMID:17053836

Effects of protein-energy malnutrition on NF-kappaB signalling in murine peritoneal macrophages.

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Fock, Ricardo Ambrósio; Rogero, Marcelo Macedo; Vinolo, Marco Aurélio Ramirez; Curi, Rui; Borges, Maria Carolina; Borelli, Primavera

2010-04-01

Protein-energy malnutrition (PEM) is an important public health problem affecting millions of people worldwide. PEM decreases resistance to infection, impairing a number of physiological processes. In unstimulated cells, NF-kappaB is kept from binding to its consensus sequence by the inhibitor I kappaB alpha, which retains NF-kappaB in the cytoplasm. Upon various signals, such as lipopolysaccharide (LPS), I kappaB alpha is rapidly degraded and NF-kappaB is induced to translocate into the nucleus, where it activates expression of various genes that participate in the inflammatory response, including those involved in the synthesis of TNF-alpha. TRAF-6 is a cytoplasmic adapter protein that links the stimulatory signal from Toll like receptor-4 to NF-kappaB. The aim of this study was to evaluate the effect of malnutrition on induction of TNF-alpha by LPS in murine peritoneal macrophages. We evaluated peritoneal cellularity, the expression of MyD88, TRAF-6, IKK, I kappaB alpha and NF-kappaB, NF-kappaB activation and TNF-alpha mRNA and protein synthesis in macrophages. Two-month-old male BALB/C mice were submitted to PEM with a low-protein diet that contained 2% protein, compared to 12% protein in the control diet. When the experimental group had lost about 20% of the original body weight, it was used in the subsequent experiments. Malnourished animals presented anemia, leucopenia and severe reduction in peritoneal cavity cellularity. TNF-alpha mRNA and protein levels of macrophages stimulated with LPS were significantly lower in malnourished animals. PEM also decreased TRAF-6 expression and NF-kappaB activation after LPS stimulation. These results led us to conclude that PEM changes NF-kB signalling pathway in macrophages to LPS stimulus.

Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

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Nikita Pozdeyev

Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

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Zhi-Juan eFeng

2015-12-01

Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

TLR4 activates NF-κB in human ovarian granulosa tumor cells

International Nuclear Information System (INIS)

Woods, Dori C.; White, Yvonne A.R.; Dau, Caroline; Johnson, A.L.

2011-01-01

Highlights: → TLR4 is expressed in human ovarian granulosa tumor cells. → Acting through TLR4, LPS and HSP60 induce a NFκB signaling cascade in human ovarian granulosa tumor cells. → NFκB activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-κB) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFα plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-κB does not sensitize GCTs to TRAIL or cisplatin.

NF-kappa B genes have a major role in Inflammatory Breast Cancer

International Nuclear Information System (INIS)

Lerebours, Florence; Vacher, Sophie; Andrieu, Catherine; Espie, Marc; Marty, Michel; Lidereau, Rosette; Bieche, Ivan

2008-01-01

IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC. We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as 'poor prognosis' breast tumor controls. Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-κB genes (NFKB1, RELA, IKBKG, NFKBIB, NFKB2, REL, CHUK), apoptosis genes (MCL1L, TNFAIP3/A20, GADD45B, FASLG, MCL1S, IER3L, TNFRSF10B/TRAILR2), immune response genes (CD40, CD48, TNFSF11/RANKL, TNFRSF11A/RANK, CCL2/MCP-1, CD40LG, IL15, GBP1), proliferation genes (CCND2, CCND3, CSF1R, CSF1, SOD2), tumor-promoting genes (CXCL12, SELE, TNC, VCAM1, ICAM1, PLAU/UPA) or angiogenesis genes (PTGS2/COX2, CXCL1/GRO1). Only two of these 35 genes (PTGS2/COX2 and CXCL1/GRO1)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of IL8 and VEGF plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC. The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC

Regulation of NF-κB oscillation by spatial parameters in true intracellular space (TiCS)

Science.gov (United States)

Ohshima, Daisuke; Sagara, Hiroshi; Ichikawa, Kazuhisa

2013-10-01

Transcription factor NF-κB is activated by cytokine stimulation, viral infection, or hypoxic environment leading to its translocation to the nucleus. The nuclear NF-κB is exported from the nucleus to the cytoplasm again, and by repetitive import and export, NF-κB shows damped oscillation with the period of 1.5-2.0 h. Oscillation pattern of NF-κB is thought to determine the gene expression profile. We published a report on a computational simulation for the oscillation of nuclear NF-κB in a 3D spherical cell, and showed the importance of spatial parameters such as diffusion coefficient and locus of translation for determining the oscillation pattern. Although the value of diffusion coefficient is inherent to protein species, its effective value can be modified by organelle crowding in intracellular space. Here we tested this possibility by computer simulation. The results indicate that the effective value of diffusion coefficient is significantly changed by the organelle crowding, and this alters the oscillation pattern of nuclear NF-κB.

The $N_f^3 g^6$ term in the pressure of hot QCD

CERN Document Server

Gynther, A; Vuorinen, A

2009-01-01

We determine the first independent part of the g^6 coefficient in the weak coupling expansion of the QCD pressure at high temperatures, the one proportional to the maximal power of the number of quark flavors N_f. In addition to introducing and developing computational methods that can be used in evaluating other parts of the expansion, our calculation provides a result that becomes dominant in the limit of large N_f and a fixed effective coupling g_{eff}^2 = g^2 N_f/2.

Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation

International Nuclear Information System (INIS)

Kim, Dae-Seok; Kim, Bora; Tahk, Hongmin; Kim, Dong-Hyun; Ahn, Eu-Ree; Choi, Changsun; Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun; Kim, Soo-Youl

2010-01-01

Research highlights: → No acute renal tubular necrotic lesions were found in TGase2 -/- mice with ischemic kidney injury. → NF-κB activation is reduced in TGase2 -/- mice with ischemic kidney injury. → Hypoxic stress did not increase NF-κB activity in MEFs from TGase2 -/- mice. → COX-2 induction is suppressed in TGase2 -/- mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2 -/- ) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-κB (NF-κB) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-κB activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-κB activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-κB activity in mouse embryogenic fibroblasts (MEFs) from TGase2 -/- mice remained at the control level while the NF-κB activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-κB activity remained at the control level in TGase2 -/- mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-κB activation in ischemic injury.

Pokemon reduces Bcl-2 expression through NF-κ Bp65: A possible mechanism of hepatocellular carcinoma.

Science.gov (United States)

Zhao, Xinkai; Ning, Qiaoming; Sun, Xiaoning; Tian, De'an

2011-06-01

To investigate the relationship among Pokemon, NF-κ B p65 and Bcl-2 in hepatoma cells. HCC cell HepG2, SMMC7721 and human fetal liver cell line LO2 cells were used, and expression of Pokemon, NF-κ B p65 and Bcl-2 in three cells were detected by real-time PCR and western blot. Then siRNA of Pokemon was applied to inhibit the expression of Pokemon and NF-κ B p65 and apoptotic rate was determined by flow cytometric analysis. Expressions of Pokemon, NF-κ B p65 and Bcl-2 in human hepatoma cell HepG2, SMMC7721 expression were significantly higher than those in human embryonic stem cells LO2. siRNA of Pokemon inhibited the expression of Pokemon, NF-κ B p65 and Bcl-2 in liver cancer cells, and significantly increased apoptosis of liver cells. While siRNA of NF-κ B p65 inhibited the expression of NF-κ B p65 and Bcl-2, but Pokemon expression in hepatoma cells had no significant change. The proto-oncogene Pokemon can inhibit P14ARF by specific transcription regulation of cell cycle and can induce tumors. In addition, Pokemon can regulate NF-κ B p65 through the expression of apoptosis repressor, and promote the development of liver cancer. It suggests signal network in the liver include the regulation of new non-classical NF-κ B regulatory pathway. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

International Nuclear Information System (INIS)

Santos, Nuno R. dos; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T.

2010-01-01

Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL

NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

Energy Technology Data Exchange (ETDEWEB)

Santos, Nuno R. dos, E-mail: nrsantos@ualg.pt; Ghezzo, Marinella N.; Silva, Ricardo C. da; Fernandes, Mónica T. [IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

2010-11-05

Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL.

DMPD: New insights into NF-kappaB regulation and function. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18775672 New insights into NF-kappaB regulation and function. Sun SC, Ley SC. Trend...ction. PubmedID 18775672 Title New insights into NF-kappaB regulation and function....s Immunol. 2008 Oct;29(10):469-78. Epub 2008 Sep 3. (.png) (.svg) (.html) (.csml) Show New insights into NF-kappaB regulation and fun

DMPD: Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. [Dynamic Macrophage Pathway CSML Database

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Full Text Available 16982211 Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Wullaer...vg) (.html) (.csml) Show Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. PubmedID 1698221...1 Title Ubiquitin: tool and target for intracellular NF-kappaB inhibitors. Author

Styrene process condensate treatment with a combination process of UF and NF for reuse.

Science.gov (United States)

Wang, Aijun; Liu, Guangmin; Huang, Jin; Wang, Lijuan; Li, Guangbin; Su, Xudong; Qi, Hong

2013-01-15

Aiming at reusing the SPC to save water resource and heat energy, a combination treatment process of UF/NF was applied to remove inorganic irons, suspended particles and little amount of organic contaminants in this article. To achieve the indexes of CODM≤5.00 mg L(-1), oil≤2.00 mg L(-1), conductivity≤10.00 μs cm(-1), pH of 6.0-8.0, the NF membrane process was adopted. It was necessary to employ a pretreatment process to reduce NF membrane fouling. Hence UF membrane as an efficient pretreatment unit was proposed to remove the inorganic particles, such as iron oxide catalyst, to meet the influent demands of NF. The effluent of UF, which was less than 0.02 mg L(-1) of total iron, went into a security filter and then was pumped into the NF process unit. High removal efficiencies of CODM, oil and conductivity were achieved by using NF process. The ABS grafting copolymerization experiment showed that the effluent of the combination process met the criteria of ABS production process, meanwhile the process could alleviate the environment pollution. It was shown that this combination process concept was feasible and successful in treating the SPC. Copyright © 2012 Elsevier B.V. All rights reserved.

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Science.gov (United States)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway

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Xudong Sun

2017-06-01

Full Text Available Background/Aims: Subacute ruminal acidosis (SARA is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Methods: Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor cultured in different pH medium (pH 7.2 or 5.5. qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. Results: The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2 and acidic (pH=5.5 medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6 and interleukin 1 beta (IL-1β, thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. Conclusion: The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway.

Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

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Kahl Brad S

2008-05-01

Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

[Prostate specific antigen and NF-kB in prostatic disease: relation with malignancy].

Science.gov (United States)

Cansino, J R; Vera, R; Rodríguez de Bethencourt, F; Bouraoui, Y; Rodríguez, G; Prieto, A; de la Peña, J; Paniagua, R; Royuela, M

2011-01-01

NF-kB (p50/p65) is a transcription factor involved in TNF-α-induced cell death resistance by promoting several antiapoptotic genes. We intend to relate the expression of NF-kB (p50 and p65) with serum levels of prostate-specific antigen (PSA), both in normal males and in those with pathologic conditions of the prostate. this study was carried out in 5 normal, 24 benign prostatic hyperplastic (BPH) and 19 patients with prostate cancer (PC). Immunohistochemical and Western blot analyses were performed on tissue and serum PSA was assayed by PSA DPC Immulite assays (Diagnostics Products Corporation, Los Angeles, CA). in controls, p65 NF-kB was not found and p50 was scantly detected in 60% normal samples in the cytoplasm of epithelial cells. Both p50 and p65 were expressed in 62.5% of the samples with BPH and in 63.2% of those with PC. Both increased its frequency of expression with higher PSA serum levels. Activation of NF-kB revealed by its nuclear translocation in prostate cancer could be related to cancer progression and elevated seric PSA levels. A better understanding of the biologic mechanism by which circulating PSA levels increase and its relation with NF-kB expression is needed. Possibly, NF-kB blockage could be used as a therapeutic target to counteract proliferation in prostate cancer. Copyright © 2010 AEU. Published by Elsevier Espana. All rights reserved.

Development of NF3 Deposit Removal Technology for the Portsmouth Gaseous Diffusion Plant

International Nuclear Information System (INIS)

Scheele, R.D.; McNamara, B.K.; Rapko, B.M.; Edwards, M.K.; Kozelisky, A.E.; Daniel, R.C.; McSweeney, T.I.; Maharas, S.J.; Weaver, P.J.; Iwamasa, K.J.; Kefgen, R.B.

2006-01-01

This paper summarizes the Battelle, Stoller, and WASTREN (BSW) team's efforts, to date, in support of the United States Department of Energy's plans to remove uranium and technetium deposits before decommissioning the Portsmouth Gaseous Diffusion Plant. The BSW team investigated nitrogen trifluoride (NF 3 ) as a safer yet effective alternative gaseous treatment to the chlorine trifluoride (ClF 3 )-elemental fluorine (F 2 ) treatment currently used to remove uranium and technetium deposits from the uranium enrichment cascade. Both ClF 3 and F 2 are highly reactive, toxic, and hazardous gases, while NF 3 , although toxic [1], is no more harmful than moth balls [2]. BSW's laboratory thermo-analytical and laboratory-scale prototype studies with NF 3 established that thermal NF 3 can effectively remove likely and potential uranium (UO 2 F 2 and UF 4 ) and technetium deposits (a surrogate deposit material, TcO 2 , and pertechnetates) by conversion to volatile compounds. Our engineering evaluations suggest that NF 3 's effectiveness could be enhanced by combining with a lesser concentration of ClF 3 . BSW's and other's studies indicate compatibility with Portsmouth materials of construction (aluminum, copper, and nickel). (authors)

Viabilidade do processamento de biscoitos com farinha de pinhão / Viability of cookie-processing with Paraná pine nut flour

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Maurício Rigo

2009-08-01

Full Text Available ResumoO pinhão é a semente do pinho ou pinheiro-do-paraná (Araucaria angustifolia de grande ocorrência no estado do Paraná. A farinha obtida é uma fonte de proteína, carboidratos e fibras e sua aplicação na indústria de alimentos poderia contribuir para melhorar o valor nutricional de vários produtos. Biscoito é o produto obtido pelo amassamento e cozimento de massa preparada com farinhas, amidos, fermentada ou não e outras substâncias alimentícias. Neste trabalho, foi estudada a elaboração de biscoito com farinha de pinhão. Foram preparadas três formulações, variando-se a adição da farinha de pinhão na formulação básica de biscoito. As amostras de biscoito com formulações de 0, 5, 10 e 20% foram submetidas a teste de aceitação. As três formulações foram bem aceitas, apresentando uma consistência semelhante ao padrão.AbstractThe seed from the evergreen species Paraná Pine (Araucaria angustifolia, which is found in Paraná State, is called “pinhão”. The “pinhão” flour is a source of protein, carbohydrates and fiber, so that its use in food industries may improve the nutritional value of several products. Cookies are made of a pastry prepared with flour, starch, with or without fermentation, and other ingredients. This research studied the production of biscuits with 5, 10 and 20% of “pinhão” flour. These three formulations were well accepted by subjects who participated in a tasting test and their texture was similar to standard cookies.

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

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Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

2010-11-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-κB pathway in irradiated cells

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Lam, R.K.K. [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); Han, Wei [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong (Hong Kong); State Key Laboratory in Marine Pollution, City University of Hong Kong (Hong Kong)

2015-12-15

Highlights: • Rescue effect was observed in both irradiated and HeLa and NIH/3T3 cells. • Novel setup and procedures to separate the rescue signals and the bystander signals. • Confirmed activation of NF-κB pathway in rescue effect using activation inhibitor. • Confirmed activation of NF-κB pathway in rescue effect using anti-NF-κB p65 antibody. - Abstract: We studied the involvement of NF-κB pathway activation in the rescue effect in HeLa and NIH/3T3 cells irradiated by α particles. Firstly, upon irradiation by 5 cGy of α particles, for both cell lines, the numbers of 53BP1 foci/cell at 12 h post-irradiation were significantly smaller when only 2.5% of the cell population was irradiated as compared to 100% irradiation, which demonstrated the rescue effect. Secondly, we studied the effect of NF-κB on the rescue effect through the use of the NF-κB activation inhibitor BAY-11-7082. Novel experimental setup and procedures were designed to prepare the medium (CM) which had conditioned the bystander cells previously partnered with irradiated cells, to ensure physical separation between rescue and bystander signals. BAY-11-7082 itself did not inflict DNA damages in the cells or have effects on activation of the NF-κB response pathway in the irradiated cells through direct irradiation. The rescue effect was induced in both cell lines by the CM, which was abrogated if BAY-11-7082 was added to the CM. Thirdly, we studied the effect of NF-κB on the rescue effect through staining for phosphorylated NF-κB (p-NF-κB) expression using the anti-NF-κB p65 (phospho S536) antibody. When the fraction of irradiated cells dropped from 100% to 2.5%, the p-NF-κB expression in the cell nuclei of irradiated NIH/3T3 cells increased significantly, while that in the cell nuclei of irradiated HeLa cells also increased although not significantly. Moreover, the p-NF-κB expression in the cell nuclei of irradiated HeLa cells and NIH/3T3 cells treated with CM also increased

Developments of fuel performance analysis codes in KEPCO NF

International Nuclear Information System (INIS)

Han, H. T.; Choi, J. M.; Jung, C. D.; Yoo, J. S.

2012-01-01

The KEPCO NF has developed fuel performance analysis and design code named as ROPER, and utility codes of XGCOL and XDNB in order to perform fuel rod design evaluation for Korean nuclear power plants. The ROPER code intends to cover full range of fuel performance evaluation. The XGCOL code is for the clad flattening evaluation and the XDNB code is for the extensive DNB propagation evaluation. In addition to these, the KEPCO NF is now in the developing stage for 3-dimensional fuel performance analysis code, named as OPER3D, using 3-dimensional FEM for the nest generation within the joint project CANDU ENERGY in order to analyze PCMI behavior and fuel performance under load following operation. Of these, the ROPER code is now in the stage of licensing activities by Korean regulatory body and the other two are almost in the final developing stage. After finishing the developing, licensing activities are to be performed. These activities are intending to acquire competitiveness, originality, vendor-free ownership of fuel performance codes in the KEPCO NF

Transcription factor NF-kB as a potential biomarker for oxidative stress

NARCIS (Netherlands)

Berg, R. van den; Haenen, G.R.M.M.; Berg, H. van den; Bast, A.

2001-01-01

There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-κB (nuclear factor-κB), in the pathogenesis of various diseases. NF-κB is involved in the control of the transcription of a variety of cellular genes that regulate the inflammatory

NF-κB-IKKβ pathway as a target for drug development: realities, challenges and perspectives.

Science.gov (United States)

Freitas, Rosana H C N; Fraga, Carlos A M

2018-02-19

Nuclear factor κB (NF-κB) comprises a family of proteins that act as transcription factors promoting the expression of many genes. Activation of NF-κB biochemical cascades is associated with the regulation of innate and adaptive immune responses and inflammation, among other physiological responses. However, genetic abnormalities and continuous stimulation of the NF-κB-IKKβ pathway are directly related to many types of inflammatory and autoimmune diseases, as well as to the genesis and survival of tumor cells. Inhibition of the NF-κB-IKKβ cascade can be considered an attractive therapeutic method for the genesis of new prototypes to combat these chronic multifactorial diseases. This review describes some prototypes and drugs that act to inhibit the NF-κB-IKKβ pathway, highlighting the realities, challenges and perspectives for therapeutic use. Although only proteasome inhibitors, such as bortezomib and carfilzomib, are a reality as therapeutically useful drugs among the known modulators of possible targets in the NF-κB-IKKβ pathway, some other prototypes described as IKKβ inhibitors have entered clinical stages as drug candidates for the control of inflammatory diseases. It is important to note that some classical drugs available on the pharmaceutical market, such as acetylsalicylic acid, were also described more recently as NF-κB pathway modulators as IKKβ inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Purinergic signaling is required for fluid shear stress-induced NF-{kappa}B translocation in osteoblasts

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Genetos, Damian C., E-mail: dgenetos@ucdavis.edu [Department of Anatomy, Cell Biology, and Physiology, School of Veterinary Medicine, University of California, Davis, CA (United States); Karin, Norman J. [Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA (United States); Geist, Derik J. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Donahue, Henry J. [Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State College of Medicine, Hershey, PA (United States); Duncan, Randall L. [Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN (United States)

2011-04-01

Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-{kappa}B. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-{kappa}B inhibitory protein I{kappa}B{alpha} and exhibited cytosolic localization of NF-{kappa}B. Under fluid shear stress, I{kappa}B{alpha} levels decreased, and concomitant nuclear localization of NF-{kappa}B was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in I{kappa}B{alpha}, and NF-{kappa}B remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X{sub 7} receptor antagonists, indicating that the P2X{sub 7} receptor is responsible for fluid shear-stress-induced I{kappa}B{alpha} degradation and nuclear accumulation of NF-{kappa}B. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced I{kappa}B{alpha} degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X{sub 7}-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-{kappa}B activity through the P2Y{sub 6} and P2X{sub 7} receptor.

MicroRNA Roles in the NF-κB Signaling Pathway during Viral Infections

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Zeqian Gao

2014-01-01

Full Text Available NF-κB signaling network is a crucial component of innate immunity. miRNAs are a subtype of small noncoding RNAs, involved in regulation of gene expression at the posttranscriptional level. Increasing evidence has emerged that miRNAs play an important role in regulation of NF-κB signaling pathway during viral infections. Both host and viral miRNAs are attributed to modulation of NF-κB activity, thus affecting viral infection and clearance. Understandings of the mechanisms of these miRNAs will open a direction for development of novel antivirus drugs.

Cell Autonomous and Non-Autonomous Functions of IKKβ and NF-κB during the Pathogenesis of Gastrointestinal Tumors

International Nuclear Information System (INIS)

Fang, Hsin-Yu; Greten, Florian R.

2011-01-01

Genetic studies describing a link between cancer and inflammation have increased recently. Activation of the transcription factor nuclear factor-κB (NF-κB) and its effector pathways has been proposed to be the missing link between these two processes. NF-κB is persistently activated in several types of tumors. However, NF-κB has a distinct role in cancer cells and in inflammatory cells. While in tumor cells NF-κB controls cell survival, in inflammatory cells NF-κB activates genes that encode pro-inflammatory cytokines which further act in a paracrine manner within the tumor microenvironment to contribute to tumorigenesis. Inactivation of NF-κB can also reduce chemoresistance and radioresistance of cancer cells. Therefore, specific NF-κB inhibition in combination with cytotoxic drugs and/or irradiation represents a very promising strategy for cancer therapy

RUNX1: A Regulator of NF-kB Signaling in Pulmonary Diseases.

Science.gov (United States)

Tang, Xiaoju; Sun, Ling; Wang, Gang; Chen, Bojiang; Luo, Fengming

2018-01-01

Runt-related transcription factor 1 (RUNX1), a member of the RUNX family, is one of the key regulatory proteins in vertebrates. RUNX1 is involved in embryonic development, hematopoiesis, angiogenesis, tumorigenesis and immune response. In the past few decades, studies mainly focused on the effect of RUNX1 on acute leukemia and cancer. Only few studies about the function of RUNX1 in the pathological process of pulmonary diseases have been reported. Recent studies have demonstrated that RUNX1 is highly expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung and that it plays a critical role in the lipopolysaccharide induced lung inflammation by regulating the NF-kB pathway. RUNX1 participates in the regulation of the NF-kB signaling pathway through interaction with IkB kinase complex in the cytoplasm or interaction with the NF-kB subunit P50. NF-kB is well-known signaling pathway necessary for inflammatory response in the lung. This review is to highlight the RUNX1 structure, isoforms and to present the mechanism that RUNX1 regulates NF-kB. This will illustrate the great potential role of RUNX1 in the inflammation signaling pathway in pulmonary diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modulation of NF-KB in rescued irradiated cells

International Nuclear Information System (INIS)

Lam, R.K.K.; Fung, Y.K.; Han, W.; Li, L.; Chiu, S.K.; Cheng, S.H.; Yu, K.N.

2015-01-01

Studies by different groups on the rescue effect, where unirradiated bystander cells mitigated the damages in the irradiated cells, since its discovery by the authors' group in 2011 were first reviewed. The properties of the rescue effect were then examined using a novel experimental set-up to physically separate the rescue signals from the bystander signals. The authors' results showed that the rescue effect was mediated through activation of the nuclear factor-KB (NF-KB) response pathway in the irradiated cells, and that the NF-KB activation inhibitor BAy -1 1-7082 did not affect the activation of this response pathway in the irradiated cells induced by direct irradiation. (authors)

Qualidade física e sensorial de biscoitos doces com fécula de mandioca Physical and sensorial quality of sweet cookies with cassava starch

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Jucyanne Carvalho Vieira

2010-12-01

Full Text Available Neste trabalho, foi avaliada a substituição de 5, 10 e 15% de farinha de trigo por fécula de mandioca na elaboração de biscoito doce. Ambas, farinha e fécula, foram submetidas à caracterização físico-química, reológica e análise térmica diferencial (DTA. Os biscoitos produzidos foram comparados por meio de análises sensoriais e microbiológicas. O resultado da análise térmica diferencial não mostrou qualquer alteração no comportamento de gelatinização do amido. O teste de aceitação sensorial mostrou que a crocância foi o único atributo que apresentou diferença significativa, indicando a viabilidade técnica de substituição da farinha de trigo por 15% de fécula de mandioca.This research evaluated the substitution of 5, 10 and 15% of wheat flour for cassava starch in sweet cookies production. Both, flour and starch were submitted to the physicochemical, rheological and differential thermal analysis (DTA. The produced cookies were compared through sensory and microbiological analyses. The DTA result didn´t show any alteration in the starch gelatinization behavior. The result of the sensory acceptance analysis showed that crispness is the unique attribute that presented significant difference, indicating the technical viability of wheat flour substitution for 15% of cassava starch.

Role of NF-κB and cytokine in experimental cancer cachexia

Institute of Scientific and Technical Information of China (English)

Wei Zhou; Zhi-Wei Jiang; Jie Tian; Jun Jiang; Ning Li; Jie-Shou Li

2003-01-01

AIM: To assess the putative involvement of NF-κB and proinflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND)on cachexia.METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing murine were inoculated subcutaneously to induce cachexia.Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNFα and IL-6 and activity of NF-κB in the spleen were investigated in all animals.RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P＜0.01), and the weight of gastrocnemius was decreased by 28.7 % (P＜0.01). No difference was found between groups in food intake (P＞0.05).Gastrocnemius weight was increased markedly (P＜0.01)body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-αand IL-6 (P＜0.01). The concentration of TNF-α (P＜0.05)and IL-6 (P＜0.01) in tumor-bearing mice was reduced after of IL-6 was slightly elevated following treatment of IND 2.0tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (ENSA). NF-κB activity a higher NF-κB activity was observed in mice treated with CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-αand IL-6 in tumor-bearing animals, which is controlled by NF-κB. Low dose of indomethacin alleviates the cachexia,decreases the activation of NF-κB and the serum levels of TNF-α and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.

ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity

Energy Technology Data Exchange (ETDEWEB)

Liu, Xin-Hua [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Bauman, William A. [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Cardozo, Christopher, E-mail: chris.cardozo@va.gov [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

2015-08-14

Transcription factors of the nuclear factor-kappa B (NF-κB) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-κB also regulates the processes of muscle atrophy. NF-κB activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-κB mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 in NF-κB mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-κB activity and determined the interactions between AnkrD1 expression and NF-κB signaling induced by TNFα in differentiating C2C12 myoblasts. TNFα upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNFα-induced transcriptional activation of NF-κB, whereas overexpression of AnkrD1 inhibited TNFα-induced NF-κB activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-κB and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-κB binding site in the AnrkD2 promoter and required NF-κB to do so. These results provide evidence of signaling integration between AnkrD1 and NF-κB pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-κB transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. - Highlights: • AnkrD1 is upregulated by TNFα and represses NF-κB-induced transcriptional activity. • AnkrD1 binds to p50 subunit of NF-κB and is recruited to NF-κB bound to chromatin. • AnkrD1 mediates a feed-back inhibitory loop

Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis

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García-Román Rebeca

2007-04-01

Full Text Available Abstract Background To define the NF-kappaB activation in early stages of hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole liver regeneration. Methods Western-blot and EMSA analyses were performed for the NF-kappaB activation. The transcriptional activity of NF-kappaB was determined by RT-PCR of the IkappaB-α mRNA. The IkappaB's degradation proteins were determined by Western-blot assay. Results We demonstrated the persistent activation of NF-kappaB during early stages of hepatocarcinogenesis, which reached maximal level 30 min after partial hepatectomy. The DNA binding and transcriptional activity of NF-kappaB, were sustained during early steps of hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a transitory NF-kappaB activation. In early stages of hepatocarconogenesis, the IkappaB-α degradation turned out to be acute and transitory, but the low levels of IkappaB-β persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-β degradation is not induced after sole partial hepatectomy. Conclusion We propose that during liver regeneration, the transitory stimulation of the transcription factor response, assures blockade of NF-kappaB until recovery of the total mass of the liver and the persistent NF-kappaB activation in early hepatocarcinogenesis may be due to IkappaB-β and IkappaB-α degradation, mainly IkappaB-β degradation, which contributes to gene transcription related to proliferation required for neoplasic progression.

Re-induction of obese body weight occurs more rapidly and at lower caloric intake in beagles.

Science.gov (United States)

Nagaoka, D; Mitsuhashi, Y; Angell, R; Bigley, K E; Bauer, J E

2010-06-01

For the purpose of investigating the mechanism of obesity-induction/re-induction including weight-cycling in beagles, a study was conducted using commercially available dog food combined with human food to mimic at home-snacking and diet-supplementation behaviours. Adult female beagles, which had free access to water and exercise, were used (n = 9). All dogs were initially offered two times their daily calculated number of calories using a dry extruded diet plus blend of canola and soybean oils and allowed to eat ad libitum. After 3 weeks, Pecan shortbread cookies were added to the diet mixture. Obesity was induced during a 19-week period with 1875-2250 kcal/day consumed, on average, during this period. The dogs were then subjected to a weight-loss regimen while consuming 490-730 kcal/day. After weight loss, a similar degree of obesity was re-induced for 17 weeks even though dogs consumed only 1125-1250 kcal/day. Body weight, body condition scores, kcal consumption and food efficiency were recorded. Results indicated that less time and fewer kcal were required to re-induce the same degree of obesity compared with the initial obesity induction. Human snack foods appeared to stimulate appetite and thus contribute to the obese state. Food efficiency was also increased during the obesity-reinduction period compared with the induction period. This information may help pet owners better understand the need to limit table scraps and human-type food snacks in dogs prone to obesity as well as weight maintenance after weight loss.

In silico CrNF, a half-metallic ferromagnetic nitride–fluoride mimicking CrO2

International Nuclear Information System (INIS)

Matar, Samir F.

2014-01-01

Isoelectronic with CrO 2 , CrNF is proposed in silico based on rutile derived structures with DFT computations. The ground state structure defined from cohesive energies is of MgUO 4 -type, characterized by short covalent Cr–N and long ionic Cr–F distances. Like CrO 2 it is a half-metallic ferromagnet with M=2 μ B /FU integer magnetization with reduced band gap at minority spins. Major difference of magnetic response to pressure characterizes CrNF as a soft ferromagnet versus hard magnetic CrO 2 . The chemical bonding properties point to prevailing covalent Cr–N versus ionic Cr–F bonding. Different synthesis routes are examined. - Highlights: • DFT identification of CrNF is based on isoelectronicity and rutile derivatives. • Similarly to CrO 2 , CrNF is a half-metallic ferromagnet with reduced band gap. • Strong pressure dependence of magnetization of CrNF oppositely to CrO 2 . • Covalent Cr–N bonding prevails in spite of the presence of ionic Cr–F. • Cohesive energies favor the synthesis for which protocols are proposed

Clinical and Molecular Consequences of NF1 Microdeletion

National Research Council Canada - National Science Library

Stephens, Karen

2007-01-01

... model of plexiform neurofibroma tunorigenesis and the conservation of recombination hotspots. Our hypothesis that genome instability occurs during NF1-tumorigenesis continues to be supported by our findings...

Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-κB Pathway

Directory of Open Access Journals (Sweden)

Tao Peng

2015-01-01

Full Text Available Andrographolide (Andro has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC. However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibited the proliferation and invasion of NPC cells (P<0.05, resp.. These anticancer activities were associated with cell apoptosis, cell death and induction of cell cycle arrest, and the downregulation of NF-κB target genes. This work provides evidence that NF-κB pathway is a potential therapeutic target and may also be indispensable in the Andro-mediated anticancer activities in nasopharyngeal carcinoma.

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences.

Science.gov (United States)

Zhang, Ye; Moreno-Villanueva, Maria; Krieger, Stephanie; Ramesh, Govindarajan T; Neelam, Srujana; Wu, Honglu

2017-05-31

In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Directory of Open Access Journals (Sweden)

Ye Zhang

2017-05-01

Full Text Available In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic Mdx and Mdx/Utrophin-/- Mice.

Directory of Open Access Journals (Sweden)

Bruce E Markham

Full Text Available Poloxamer 188 NF (national formulary (NF grade of P-188 improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin-/- (dko muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c. injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone's effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.

Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

Science.gov (United States)

Ricketts, Christopher J.; Wei, Darmood; Yang, Youfeng; Baranes, Sarah M.; Gibbs, Benjamin K.; Ohanjanian, Lernik; Spencer Krane, L.; Scroggins, Bradley T.; Keith Killian, J.; Wei, Ming-Hui; Kijima, Toshiki; Meltzer, Paul S.; Citrin, Deborah E.; Neckers, Len; Vocke, Cathy D.; Marston Linehan, W.

2018-01-01

Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15–20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation. The Src family kinase member Yes also regulates YAP1 transcriptional activity. This study investigated the importance of YAP and Yes activity in three NF2-deficient PRCC cell lines. NF2-deficency correlated with increased expression of YAP1 transcriptional targets and siRNA-based knockdown of YAP1 and Yes1 downregulated this pathway and dramatically reduced cell viability. Dasatinib and saracatinib have potent inhibitory effects on Yes and treatment with either resulted in downregulation of YAP1 transcription targets, reduced cell viability, and G0-G1 cell cycle arrest. Xenograft models for NF2-deficient PRCC also demonstrated reduced tumor growth in response to dasatinib. Thus, inhibiting Yes and the subsequent transcriptional activity of YAP1 had a substantial anti-tumor cell effect both in vitro and in vivo and may provide a viable therapeutic approach for patients with NF2-deficient PRCC. PMID:29535838

(-)-Epigallocatechin gallate inhibition of osteoclastic differentiation via NF-κB

International Nuclear Information System (INIS)

Lin, R.-W.; Chen, C.-H.; Wang, Y.-H.; Ho, M.-L.; Hung, S.-H.; Chen, I.-S.; Wang, G.-J.

2009-01-01

People who regularly drink tea have been found to have a higher bone mineral density (BMD) and to be at less risk of hip fractures than those who do not drink it. Green tea catechins such as (-)-epigallocatechin gallate (EGCG) have been reported to increase osteogenic functioning in mesenchymal stem cells. However, its effect on osteoclastogenesis remains unclear. In this study, we investigated the effect of EGCG on RANKL-activation osteoclastogenesis and NF-κB in RAW 264.7, a murine preosteoclast cell line. EGCG (10-100 μM) significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in murine RAW 264.7 cells and bone marrow macrophages (BMMs). EGCG appeared to target osteoclastic differentiation at an early stage but had no cytotoxic effect on osteoclast precursors. In addition, it significantly inhibited RANKL-induced NF-κB transcriptional activity and nuclear translocation. We conclude that EGCG inhibits osteoclastogenesis through its activation of NF-κB.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Energy Technology Data Exchange (ETDEWEB)

Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others

2015-07-10

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

International Nuclear Information System (INIS)

Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao

2015-01-01

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy

Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation.

Science.gov (United States)

Yamaguchi, Masayoshi; Weitzmann, M Neale

2011-01-01

Several bone protective factors are reported to exhibit stimulatory activities on bone formation coupled with inhibitory effects on bone resorption; one such factor is vitamin K2. Vitamin K species [K1 (phylloquinone) and K2 (menaquinone)] have long been associated with bone protective activities and are receiving intense interest as nutritional supplements for the prevention or amelioration of bone disease in humans. However, the mechanisms of vitamin K action on the skeleton are poorly defined. Activation of the nuclear factor κB (NF-κB) signal transduction pathway is essential for osteoclast formation and resorption. By contrast, NF-κB signaling potently antagonizes osteoblast differentiation and function, prompting us to speculate that NF-κB antagonists may represent a novel class of dual anti-catabolic and pro-anabolic agents. We now show that vitamin K2 action on osteoblast and osteoclast formation and activity is accomplished by down-regulating basal and cytokine-induced NF-κB activation, by increasing IκB mRNA, in a γ-carboxylation-independent manner. Furthermore, vitamin K2 prevented repression by tumor necrosis factor α (TNFα) of SMAD signaling induced by either transforming growth factor ß (TGFß) or bone morphogenetic protein-2 (BMP-2). Vitamin K2 further antagonized receptor activator of NF-κB (RANK) ligand (RANKL)-induced NF-κB activation in osteoclast precursors. Our data provide a novel mechanism to explain the dual pro-anabolic and anti-catabolic activities of vitamin K2, and may further support the concept that pharmacological modulation of NF-κB signal transduction may constitute an effective mechanism for ameliorating pathological bone loss and for promoting bone health.

Angiogenesis and Therapeutic Approaches to NF1 Tumors

National Research Council Canada - National Science Library

Muir, David F

2007-01-01

.... Invivo and in vitro models were used to firmly conclude that Nf1 haploinsufficiency in endothelial cells results inexaggerated proliferation and angiogenesis in response to key pro-angiogenic factors...

Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors

Science.gov (United States)

2016-10-01

development of the principal discipline(s) of the project? • We have learned that the drug PEGPH20, which degrades a component of connective tissue called...AWARD NUMBER: W81XWH-15-1-0114 TITLE: Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors PRINCIPAL INVESTIGATOR...14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER NF140089 Targeting the ECM to Enhance Drug Delivery in Nf1-Associated Nerve Sheath Tumors 5b

C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.

Directory of Open Access Journals (Sweden)

Evangeline W Cornwell

Full Text Available Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n. IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes.

Human T-cell leukemia virus type 1 (HTLV-1 tax requires CADM1/TSLC1 for inactivation of the NF-κB inhibitor A20 and constitutive NF-κB signaling.

Directory of Open Access Journals (Sweden)

Rajeshree Pujari

2015-03-01

Full Text Available Persistent activation of NF-κB by the Human T-cell leukemia virus type 1 (HTLV-1 oncoprotein, Tax, is vital for the development and pathogenesis of adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. K63-linked polyubiquitinated Tax activates the IKK complex in the plasma membrane-associated lipid raft microdomain. Tax also interacts with TAX1BP1 to inactivate the NF-κB negative regulatory ubiquitin-editing A20 enzyme complex. However, the molecular mechanisms of Tax-mediated IKK activation and A20 protein complex inactivation are poorly understood. Here, we demonstrated that membrane associated CADM1 (Cell adhesion molecule1 recruits Ubc13 to Tax, causing K63-linked polyubiquitination of Tax, and IKK complex activation in the membrane lipid raft. The c-terminal cytoplasmic tail containing PDZ binding motif of CADM1 is critical for Tax to maintain persistent NF-κB activation. Finally, Tax failed to inactivate the NF-κB negative regulator ubiquitin-editing enzyme A20 complex, and activate the IKK complex in the lipid raft in absence of CADM1. Our results thus indicate that CADM1 functions as a critical scaffold molecule for Tax and Ubc13 to form a cellular complex with NEMO, TAX1BP1 and NRP, to activate the IKK complex in the plasma membrane-associated lipid rafts, to inactivate NF-κB negative regulators, and maintain persistent NF-κB activation in HTLV-1 infected cells.

AAV-based shRNA silencing of NF-κB ameliorates muscle pathologies in mdx mice.

Science.gov (United States)

Yang, Q; Tang, Y; Imbrogno, K; Lu, A; Proto, J D; Chen, A; Guo, F; Fu, F H; Huard, J; Wang, B

2012-12-01

Chronic inflammation, promoted by an upregulated NF-kappa B (NF-κB) pathway, has a key role in Duchenne muscular dystrophy (DMD) patients' pathogenesis. Blocking the NF-κB pathway has been shown to be a viable approach to diminish chronic inflammation and necrosis in the dystrophin-defective mdx mouse, a murine DMD model. In this study, we used the recombinant adeno-associated virus serotype 9 (AAV9) carrying an short hairpin RNA (shRNA) specifically targeting the messenger RNA of NF-κB/p65 (p65-shRNA), the major subunit of NF-κB associated with chronic inflammation in mdx mice. We examined whether i.m. AAV9-mediated delivery of p65-shRNA could decrease NF-κB activation, allowing for amelioration of muscle pathologies in 1- and 4-month-old mdx mice. At 1 month after treatment, NF-κB/p65 levels were significantly decreased by AAV gene transfer of p65-shRNA in the two ages of treatment groups, with necrosis significantly decreased compared with controls. Quantitative analysis revealed that central nucleation (CN) of the myofibers of p65-shRNA-treated 1-month-old mdx muscles was reduced from 67 to 34%, but the level of CN was not significantly decreased in treated 4-month-old mdx mice. Moreover, delivery of the p65-shRNA enhanced the capacity of myofiber regeneration in old mdx mice treated at 4 months of age when the dystrophic myofibers were most exhausted; however, such p65 silencing diminished the myofiber regeneration in young mdx mice treated at 1 month of age. Taken together, these findings demonstrate that the AAV-mediated delivery of p65-shRNA has the capacity to ameliorate muscle pathologies in mdx mice by selectively reducing NF-κB/p65 activity.

PUMA and NF-kB Are Cell Signaling Predictors of Reovirus Oncolysis of Breast Cancer.

Science.gov (United States)

Thirukkumaran, Chandini; Shi, Zhong-Qiao; Thirukkumaran, Ponnampalam; Luider, Joanne; Kopciuk, Karen; Spurrell, Jason; Elzinga, Kate; Morris, Don

2017-01-01

Reovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour. In the present study global gene expression profiling was utilized as a preliminary roadmap to tease-out pivotal molecules involved in reovirus induced apoptosis in breast cancer. Reovirus treated HTB133 and MCF7 breast cancer cells revealed transcriptional alteration of a defined subset of apoptotic genes and members of the nuclear factor-kappa B (NF-kB) family and p53 upregulated modulator of apoptosis (PUMA) were prominent. Since NF-kB can paradoxically suppress or promote apoptosis in cancer, the significance of NF-kB in reovirus oncolysis of breast cancer was investigated. Real time PCR analysis indicated a 2.9-4.3 fold increase in NF-kB p65 message levels following reovirus infection of MCF7 and HTB133, respectively. Nuclear translocation of NF-kB p65 protein was also dramatically augmented post reovirus treatment and correlated with enhanced DNA binding. Pharmacologic inhibition of NF-kB lead to oncolytic protection and significant down regulation of PUMA message levels. PUMA down regulation using siRNA suppressed reovirus oncolysis via significantly repressed apoptosis in p53 mutant HTB133 cells. This study demonstrates for the first time that a prominent pathway of reovirus oncolysis of breast cancer is mediated through NF-kB and that PUMA upregulation is dependent on NF-kB activation. These findings represent potential therapeutic indicators of reovirus treatment in future clinical trials.

Histamine Induces Bovine Rumen Epithelial Cell Inflammatory Response via NF-κB Pathway.

Science.gov (United States)

Sun, Xudong; Yuan, Xue; Chen, Liang; Wang, Tingting; Wang, Zhe; Sun, Guoquan; Li, Xiaobing; Li, Xinwei; Liu, Guowen

2017-01-01

Subacute ruminal acidosis (SARA) is a common disease in high-producing lactating cows. Rumenitis is the initial insult of SARA and is associated with the high concentrations of histamine produced in the rumen of dairy cows during SARA. However, the exact mechanism remains unclear. The objective of the current study is to investigate whether histamine induces inflammation of rumen epithelial cells and the underlying mechanism of this process. Bovine rumen epithelial cells were cultured and treated with different concentrations of histamine and pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) cultured in different pH medium (pH 7.2 or 5.5). qRT-PCR, Western-blotting, ELISA and immunocytofluorescence were used to evaluate whether histamine activated the NF-κB pathway and inflammatory cytokines. The results showed that histamine significantly increased the activity of IKK β and the phosphorylation levels of IκB α, as well as upregulated the mRNA and protein expression levels of NF-κB p65 in the rumen epithelial cells cultured in neutral (pH=7.2) and acidic (pH=5.5) medium. Furthermore, histamine treatment also significantly increased the transcriptional activity of NF-κB p65. High expression and transcriptional activity of NF-κB p65 significantly increased the mRNA expressions and concentrations of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β), thereby inducing the inflammatory response in bovine rumen epithelial cells. However, inhibition of NF-κB p65 by PDTC significantly decreased the expressions and concentrations of the inflammatory cytokines induced by histamine in the rumen epithelial cells cultured in the neutral and acidic medium. The present data indicate that histamine induces the inflammatory response of bovine rumen epithelial cells through the NF-κB pathway. © 2017 The Author(s). Published by S. Karger AG, Basel.

Influence of 17β-estradiol treatment on the expression of NF-κB in complete hydatidiform mole culture

Directory of Open Access Journals (Sweden)

Tatit Nurseta

2013-12-01

Full Text Available Background:  Genetic evidence has established a role of nuclear factor kappa B (NF-κB signaling in oncogenesis. However, activity of NF-κB in complete hydatidiform mole (CHM cell culture under 17β-estradiol (E2 treatment is not yet known. Recently, a positive cross-talk between estrogen receptor (ER and NF-κB to promote survival and progress of cancer cells to a more aggressive phenotype was established. In the present study, we examined the influence of E2 treatment on the NF-κB expression in CHM’s culture.Methods:  This experimental study measured the expression of NF-κB in CHM culture treated with E2: 10, 100, 300, 600, and 1000 pg/mL and without E2. Imunohistochemistry staining was used to assess the expression of NF-κB. Microphotographs were taken using 400x magnification. Adobe photoshop CS2 was used to assess the NF-κB expression in cell nucleus. The lower the color intensity of cell RGBbv, is the higher the expression of NF-κB in cells. ANOVA test was performed to compare the expression of NF-κB.Results: NF-κB expression as indicated by color intensity in control group was 114.84 ± 9.02. NF-κB expression in E2 treatment groups were respectively: E2 10 pg/mL: 106.30 ± 13.95; E2 100 pg/mL: 82.47 ± 4.72; E2 300 pg/mL: 82.24 ± 2.67; E2 600 pg/mL: 69.05 ± 6.47; E2 1000 pg/mL: 68.49 ± 2.37. There was progressive decline in color intensity of cells with E2 treatment indicating the increase expression of NF-κB. Significant differences with the control group occurred in doses of E2 100, 300, 600, dan 1000 pg/mL.Conclusion: Treatment of CHM trophoblast culture with escalating doses of E2 was associated with the increase of NF-κB expression in a dose dependent manner. (Med J Indones. 2013;22:197-201. doi: 10.13181/mji.v22i4.599Keywords: 17-β Estradiol, Hydatidiform mole, NF-κB

DMPD: NF-kappaB activation by reactive oxygen species: fifteen years later. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16723122 NF-kappaB activation by reactive oxygen species: fifteen years later. Gloi...svg) (.html) (.csml) Show NF-kappaB activation by reactive oxygen species: fifteen years later. PubmedID 167...23122 Title NF-kappaB activation by reactive oxygen species: fifteen years later.

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Science.gov (United States)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo. PMID:22829125

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Energy Technology Data Exchange (ETDEWEB)

Kanduri, M; Tobin, G [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden); Åleskog, A [Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala (Sweden); Nilsson, K; Rosenquist, R [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden)

2011-03-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo.

Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

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Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

2014-01-01

Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma.

Science.gov (United States)

Harhaj, Edward William; Giam, Chou-Zen

2018-05-03

The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4+ malignancy in 3-5% of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1 infected T cells. However, constitutive NF-κB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming NF-κB-induced senescence can selectively undergo clonal expansion after HTLV-1 infection. Tax expression is often silenced in the majority of ATLL due to genetic alterations in the tax gene or DNA hypermethylation of the 5'-LTR. Despite the loss of Tax, NF-κB activation remains persistently activated in ATLL due to somatic mutations in genes in the T/B-cell receptor (T/BCR) and NF-κB signaling pathways. In this review, we focus on the key events driving Tax-dependent and independent mechanisms of NF-κB activation during the multi-step process leading to ATLL. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

p55PIK regulates alpha-fetoprotein expression through the NF-κB signaling pathway.

Science.gov (United States)

Ye, Guoguo; Sun, Ge; Cheng, Zhikui; Zhang, Lei; Hu, Kanghong; Xia, Xianmin; Zhou, Yin

2017-12-15

Alpha-fetoprotein (AFP) is regarded as a diagnostic and prognostic biomarker and a potential therapeutic target for hepatocellular carcinoma (HCC). However, the regulation of AFP expression in HCC remains poorly understood. This study aimed to investigate the mechanism by which AFP expression is regulated by p55PIK, an isoform of PI3K. Human HCC cell lines (HepG2 and Huh-7) were treated with p55PIK specific competitive inhibitor or shRNA, or p55PIK overexpression vector, in the absence or presence of NF-κB inhibitor PDTC. AFP expression was detected by quantitative real-time PCR and Western blotting. NF-κB responsive elements in AFP enhancer region were characterized by luciferase reporter assay. p55PIK significantly stimulated the expression of AFP by activating NF-κB signaling pathway in HCC cells. Furthermore, two NF-κB binding sites in AFP enhancer region were identified to be primarily responsible for p55PIK mediated upregulation of AFP expression. p55PIK/NF-κB signaling plays an important role in the upregulation of AFP expression in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

EVALUACIÓN DE GALLETAS DULCES TIPO WAFER A BASE DE HARINA DE ARRACACHA (Arracacia xanthorrhiza B. EVALUATION OF WAFER TYPE SWEET COOKIES BASED UPON ARRACACHA FLOUR (Arracacia xanthorrhiza B.

Directory of Open Access Journals (Sweden)

Auris Damely García Méndez

2007-12-01

Full Text Available Para diversificar el uso de la harina de arracacha (Arracacia xanthorrhiza, se evaluó su potencialidad en la elaboración de una galleta tipo wafer con propiedades nutricionales, partiendo de una harina compuesta de trigo con 10 y 12% de harina de arracacha. La metodología permitió determinar en la galletas las características físicas (humedad, actividad de agua, pH y color, composición química proximal, funcionales (capacidad de absorción de agua y aceite de la masa y la estabilidad comercial por tres meses almacenamiento. Los resultados mostraron que la harina compuesta, contribuyó a un ligero incremento en la fracciones de fibra, ceniza y almidón resistente en las galletas. Mientras, las propiedades funcionales de la mezcla para elaborar las galletas indicaron una adecuada interacción de los ingredientes, alta absorción de agua, pero una menor capacidad de absorción de aceite en la masa, originando cambios en la textura de la galleta horneada al compararla con la galleta de trigo. En anaquel, se mantuvieron las características fisicoquímicas de la galletas, coincidiendo con las especificaciones de la normas Covenin (Comisión Venezolana de Normas Industriales nº 1483-2001, siendo esto atribuido al bajo contenido de humedad y actividad de agua. En conclusión, el uso de la harina de arracacha en una relación de 12%, resultó un ingrediente adecuado en la elaboración de galletas con alta preferencia sensorial, constituyendo una alternativa como fuente de fibra dietética.In order to diversify the use of arracacha flour (Arracacia xanthorrhiza, an evaluation was made upon its potentiality, in the manufacture of a wafer type sweet cookie, with nutritional properties; starting from a composite flour of wheat and 10-12% of arracacha flour. The methodology allowed to evaluate physical characteristics (humidity, water activity, pH and color, proximal chemical composition, functional characteristics (water and oil absorption capacity

The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells.

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Osamu Takase

Full Text Available NF-κB signaling plays an essential role in maintaining the undifferentiated state of embryonic stem (ES cells. However, opposing roles of NF-κB have been reported in mouse and human ES cells, and the role of NF-κB in human induced pluripotent stem (iPS cells has not yet been clarified. Here, we report the role of NF-κB signaling in maintaining the undifferentiated state of human iPS cells. Compared with differentiated cells, undifferentiated human iPS cells showed an augmentation of NF-κB activity. During differentiation induced by the removal of feeder cells and FGF2, we observed a reduction in NF-κB activity, the expression of the undifferentiation markers Oct3/4 and Nanog, and the up-regulation of the differentiated markers WT-1 and Pax-2. The specific knockdown of NF-κB signaling using p65 siRNA also reduced the expression of Oct3/4 and Nanog and up-regulated WT-1 and Pax-2 but did not change the ES-like colony formation. Our results show that the augmentation of NF-κB signaling maintains the undifferentiated state of human iPS and suggest the importance of this signaling pathway in maintenance of human iPS cells.

Gelam honey attenuates carrageenan-induced rat paw inflammation via NF-κB pathway.

Directory of Open Access Journals (Sweden)

Saba Zuhair Hussein

Full Text Available The activation of nuclear factor kappa B (NF-κB plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o. and NSAID Indomethacin (10 mg/kg, p.o., in two time points (1 and 7 days. Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50 and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α.

Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis.

Science.gov (United States)

Poulos, Michael G; Ramalingam, Pradeep; Gutkin, Michael C; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J P; Elemento, Olivier; Levine, Ross L; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B; Shim, Jae-Hyuck; Butler, Jason M

2016-12-21

Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.

Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis

Science.gov (United States)

Poulos, Michael G.; Ramalingam, Pradeep; Gutkin, Michael C.; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J. P.; Elemento, Olivier; Levine, Ross L.; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B.; Shim, Jae-Hyuck; Butler, Jason M.

2016-01-01

Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens. PMID:28000664

PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65

Science.gov (United States)

Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Kim, Jin Man; Huang, Song-Mei; Choi, Seung-Won; Kim, Sun-Hwan; Sohn, Kyung-Cheol; Ro, Hyunju; Lee, Ji Hoon; Lu, Tao; Stark, George R.; Shen, Han-Ming; Liu, Zheng-gang; Park, Jongsun; Hur, Gang Min

2014-01-01

Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that plant homeodomain finger protein 20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In plant homeodomain finger protein 20-overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between plant homeodomain finger protein 20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that plant homeodomain finger protein 20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies plant homeodomain finger protein 20 as a novel regulator of NF-κB activation and suggests that elevated expression of plant homeodomain finger protein 20 may drive constitutive NF-κB activation in some cancers. PMID:23797602

NF-1 Dependent Gene Regulation in Drosophila Melanogaster

National Research Council Canada - National Science Library

Zhong, Yi

2004-01-01

.... We have used an Affymetrix whole genome chip, containing all 13,500 genes of the fruit fly Drosophila, to identify 93 genes with altered expression patterns in flies that have no NF1 protein compared...

NIK and IKKbeta interdependence in NF-kappaB signalling--flux analysis of regulation through metabolites.

Science.gov (United States)

Kim, Hong-Bum; Evans, Iona; Smallwood, Rod; Holcombe, Mike; Qwarnstrom, Eva E

2010-02-01

Activation of the transcription factor NF-kappaB is central to control of immune and inflammatory responses. Cytokine induced activation through the classical or canonical pathway relies on degradation of the inhibitor, IkappaBalpha and regulation by the IKKbeta kinase. In addition, the NF-kappaB is activated through the NF-kappaB-inducing kinase, NIK. Analysis of the IKK/NIK inter-relationship and its impact on NF-kappaB control, were analysed by mathematical modelling, using matrix formalism and stoichiometrically balanced reactions. The analysis considered a range of bio-reactions and core metabolites and their role in relation to kinase activation and in control of specific steps of the NF-kappaB pathway. The model predicts a growth-rate and time-dependent transfer of the primary kinase activity from IKKbeta to NIK. In addition, it suggests that NIK/IKKbeta interdependence is controlled by intermediates of phosphoribosylpyrophosphate (PRPP) within the glycolysis pathway, and thus, identifies a link between specific metabolic events and kinase activation in inflammatory signal transduction. Subsequent in vitro experiments, carried out to validate the impact of IKK/NIK interdependence, confirmed signal amplification at the level of the NF-kappaB/IkappaBalpha complex control in the presence of both kinases. Further, they demonstrate that the induced potentiation is due to synergistic enhancement of relA-dependent activation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

XEDAR activates the non-canonical NF-κB pathway

International Nuclear Information System (INIS)

Verhelst, Kelly; Gardam, Sandra; Borghi, Alice; Kreike, Marja; Carpentier, Isabelle; Beyaert, Rudi

2015-01-01

Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20

XEDAR activates the non-canonical NF-κB pathway

Energy Technology Data Exchange (ETDEWEB)

Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Gardam, Sandra, E-mail: s.gardam@garvan.org.au [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Borghi, Alice, E-mail: Alice.Borghi@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Kreike, Marja, E-mail: Marja.Kreike@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Carpentier, Isabelle, E-mail: Isabelle.Carpentier@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Beyaert, Rudi, E-mail: Rudi.Beyaert@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium)

2015-09-18

Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.

NiO-NF/MWCNT nanocomposite catalyst as a counter electrode for high performance dye-sensitized solar cells

Science.gov (United States)

Raissan Al-bahrani, Majid; Liu, Linfeng; Ahmad, Waqar; Tao, Jiayou; Tu, Fanfan; Cheng, Ze; Gao, Yihua

2015-03-01

In this paper, we fabricated nickel oxide nanofilament/multiwall carbon nanotubes (NiO-NF/MWCNT) nanocomposite by a simple hydrothermal synthesis method as a counter- electrode (CE) in a dye-sensitized solar cell (DSSC). Transmission electron microscopy, scanning electron microscopy images and X-ray diffraction analysis clearly indicated the formation of NiO-NF/MWCNT nanocomposite. The electro-chemical properties of NiO-NF/MWCNT CE are studied by cyclic voltammetry and electrochemical impedance spectroscopy. In particular, current-voltage measurements indicated superior power conversion efficiency (PCE) of 7.63% of the NiO-NF/MWCNT CE compared to 6.72% for the platinum (Pt). The superior photovoltaic performance and low cost of the NiO-NF/MWCNT nanocomposite can be potentially exploited as a new counter-electrode in DSSCs.

An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

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Baochun Zhang

2015-05-01

Full Text Available Diffuse large B cell lymphoma (DLBCL is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-κB pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-κB pathway in DLBCL development.

Development and Characterisation of a Novel NF-κB Reporter Cell Line for Investigation of Neuroinflammation

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Marie-Theres Zeuner

2017-01-01

Full Text Available Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer’s disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry, and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to tumour necrosis factor alpha (TNFα and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologics in neural cells.

Correlation of NF-κB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Yan, Ming; Xu, Qin; Zhang, Ping; Zhou, Xiao-jian; Zhang, Zhi-yuan; Chen, Wan-tao

2010-01-01

Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets

Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1

Science.gov (United States)

Kühnisch, Jirko; Seto, Jong; Lange, Claudia; Schrof, Susanne; Stumpp, Sabine; Kobus, Karolina; Grohmann, Julia; Kossler, Nadine; Varga, Peter; Osswald, Monika; Emmerich, Denise; Tinschert, Sigrid; Thielemann, Falk; Duda, Georg; Seifert, Wenke; el Khassawna, Thaqif; Stevenson, David A.; Elefteriou, Florent; Kornak, Uwe; Raum, Kay; Fratzl, Peter; Mundlos, Stefan; Kolanczyk, Mateusz

2014-01-01

Bone fragility due to osteopenia, osteoporosis or debilitating focal skeletal dysplasias is a frequent observation in the Mendelian disease Neurofibromatosis type 1 (NF1). To determine the mechanisms underlying bone fragility in NF1 we analyzed two conditional mouse models, Nf1Prx1 (limb knock-out) and Nf1Col1 (osteoblast specific knock-out), as well as cortical bone samples from individuals with NF1. We examined mouse bone tissue with micro-computed tomography, qualitative and quantitative histology, mechanical tensile analysis, small-angle X-ray scattering (SAXS), energy dispersive X-ray spectroscopy (EDX), and scanning acoustic microscopy (SAM). In cortical bone of Nf1Prx1 mice we detected ectopic blood vessels that were associated with diaphyseal mineralization defects. Defective mineral binding in the proximity of blood vessels was most likely due to impaired bone collagen formation, as these areas were completely devoid of acidic matrix proteins and contained thin collagen fibers. Additionally, we found significantly reduced mechanical strength of the bone material, which was partially caused by increased osteocyte volume. Consistent with these observations, bone samples from individuals with NF1 and tibial dysplasia showed increased osteocyte lacuna volume. Reduced mechanical properties were associated with diminished matrix stiffness, as determined by SAM. In line with these observations, bone tissue from individuals with NF1 and tibial dysplasia showed heterogeneous mineralization and reduced collagen fiber thickness and packaging. Collectively, the data indicate that bone fragility in NF1 tibial dysplasia is partly due to an increased osteocyte-related micro-porosity, hypomineralization, a generalized defect of organic matrix formation, exacerbated in the regions of tensional and bending force integration, and finally persistence of ectopic blood vessels associated with localized macro-porotic bone lesions. PMID:24465906

NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

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Haiwen Ni

Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis.

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Malaponte, Grazia; Signorelli, Salvatore S; Bevelacqua, Valentina; Polesel, Jerry; Taborelli, Martina; Guarneri, Claudio; Fenga, Concettina; Umezawa, Kazou; Libra, Massimo

2015-01-01

Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), matrix metalloproteases-9 (MMP-9), vascular endothelial growth factor (VEGF), tissue factor (TF), fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+). All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.

Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

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Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

2012-01-01

Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

International Nuclear Information System (INIS)

Leung, Kin Chung; Li, Ming-Yue; Leung, Billy C.S.; Hsin, Michael K.Y.; Mok, Tony S.K.; Underwood, Malcolm J.; Chen, George G.

2010-01-01

Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

The three-loop splitting functions Pqg(2) and Pgg(2 ,NF)

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Ablinger, J.; Behring, A.; Blümlein, J.; De Freitas, A.; von Manteuffel, A.; Schneider, C.

2017-09-01

We calculate the unpolarized twist-2 three-loop splitting functions Pqg(2) (x) and Pgg(2 ,NF) (x) and the associated anomalous dimensions using massive three-loop operator matrix elements. While we calculate Pgg(2 ,NF) (x) directly, Pqg(2) (x) is computed from 1200 even moments, without any structural prejudice, using a hierarchy of recurrences obtained for the corresponding operator matrix element. The largest recurrence to be solved is of order 12 and degree 191. We confirm results in the foregoing literature.

NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

International Nuclear Information System (INIS)

Wang, Yi; Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing

2011-01-01

Highlights: → Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. → Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. → P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. → Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the regulation of foam

NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

Energy Technology Data Exchange (ETDEWEB)

Wang, Yi, E-mail: wangyi2004a@126.com [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China); Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China)

2011-08-05

Highlights: {yields} Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. {yields} Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. {yields} P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. {yields} Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the

NF-κB–YY1–miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma

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Wang, Huating; Garzon, Ramiro; Sun, Hao; Ladner, Katherine J.; Singh, Ravi; Dahlman, Jason; Cheng, Alfred; Hall, Brett M.; Qualman, Stephen J.; Chandler, Dawn S.; Croce, Carlo M.; Guttridge, Denis C.

2008-01-01

SUMMARY Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and Rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts miR-29 is repressed by NF-κB acting through YY1 and the Polycomb. During myogenesis, NF-κB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-κB-YY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its pro-myogenic function. Together, results identify a NF-κB–YY1–miR-29 regulatory circuit whose disruption may contribute to RMS. SIGNIFICANCE MicroRNAs regulate skeletal myogenesis, but their impact in muscle diseases is not well understood. Here we describe miR-29 as an enhancer of myogenic differentiation and a suppressor of RMS. We find that miR-29 exists in a regulatory circuit involving NF-κB and YY1. In myoblasts NF-B acts through YY1 to epigenetically suppress miR-29, while during differentiation miR-29 is induced to facilitate myogenesis by a negative feedback on YY1. Significantly, RMS tumors lose miR-29 due to an elevation in NF-B and YY1, and readjustment of miR-29 levels in RMS stimulates differentiation. Thus, myogenesis is dependent on NF-κB–YY1–miR-29 circuitry whose dysfunction may contribute to RMS pathogenesis. Such findings offer potential avenues for the diagnosis and treatment of muscle relevant cancers. PMID:18977326

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

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Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

Science.gov (United States)

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

WRI1-1, ABI5, NF-YA3 and NF-YC2 increase oil biosynthesis in coordination with hormonal signaling during fruit development in oil palm.

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Yeap, Wan-Chin; Lee, Fong-Chin; Shabari Shan, Dilip Kumar; Musa, Hamidah; Appleton, David Ross; Kulaveerasingam, Harikrishna

2017-07-01

The oil biosynthesis pathway must be tightly controlled to maximize oil yield. Oil palm accumulates exceptionally high oil content in its mesocarp, suggesting the existence of a unique fruit-specific fatty acid metabolism transcriptional network. We report the complex fruit-specific network of transcription factors responsible for modulation of oil biosynthesis genes in oil palm mesocarp. Transcriptional activation of EgWRI1-1 encoding a key master regulator that activates expression of oil biosynthesis genes, is activated by three ABA-responsive transcription factors, EgNF-YA3, EgNF-YC2 and EgABI5. Overexpression of EgWRI1-1 and its activators in Arabidopsis accelerated flowering, increased seed size and oil content, and altered expression levels of oil biosynthesis genes. Protein-protein interaction experiments demonstrated that EgNF-YA3 interacts directly with EgWRI1-1, forming a transcription complex with EgNF-YC2 and EgABI5 to modulate transcription of oil biosynthesis pathway genes. Furthermore, EgABI5 acts downstream of EgWRKY40, a repressor that interacts with EgWRKY2 to inhibit the transcription of oil biosynthesis genes. We showed that expression of these activators and repressors in oil biosynthesis can be induced by phytohormones coordinating fruit development in oil palm. We propose a model highlighting a hormone signaling network coordinating fruit development and fatty acid biosynthesis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Zhang, Mingzhi; Xu-Monette, Zijun Y; Li, Ling

2016-01-01

It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-kB subunits and involved in the classical NF-kB pathway. However, the prognostic and biological significance of RelA/p65 is equivoca...

KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation

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Prerana Jha

2017-11-01

Full Text Available KLF2 (Kruppel-like factor 2 is a member of the zinc finger transcription factor family, which critically regulates embryonic lung development, function of endothelial cells and maintenance of quiescence in T-cells and monocytes. It is expressed in naïve T-cells and monocytes, however its level of expression decreases during activation and differentiation. KLF2 also plays critical regulatory role in various inflammatory diseases and their pathogenesis. Nuclear factor-kappaB (NF-κB is an important inducer of inflammation and the inflammation is mediated through the transcription of several proinflammatory cytokines, chemokines and adhesion molecules. So, both transcriptional factors KLF2 and NF-κB are being associated with the similar cellular functions and their maintenance. It was shown that KLF2 regulates most of the NF-κB-mediated activities. In this review, we focused on emphasizing the involvement of KLF2 in health and disease states and how they interact with transcriptional master regulator NF-κB.

Inhibition of NF-κB activity in rabbit vascular smooth muscle cells by lovastatin

International Nuclear Information System (INIS)

Luan Zhaoxia; Lan Xiaoli

2003-01-01

Nuclear factor NF-κB is believed to play an important role in regulating the production of matrix metalloproteinase (MMPs), which induce atherosclerosis, restenosis and plaque rupture. We incubated rabbit vascular smooth muscle cells (RVSMCs) with 5 μmol/L lovastatin in the presence of IL-1-α and PDGF BB (20 μg/L, respectively) to study whether lovastatin inhibited NF-κB binding activity induced by IL-1 and PDGF. The NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); MMP-1 and MMP-3 were measured by western blotting; and MMP-9 was detected by zymography. The result showed that lovastatin strongly reduced NF-κB activity upregulated by IL-1 combined with PDGF, and lovastatin also dose-dependently inhibited the expression of MMP-1, -3 and -9 induced by IL-1 and PDGF. It suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction

TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.

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Karim J Brandt

Full Text Available Localization of Toll-like receptors (TLR in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.

Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

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Si, Jijian; Yang, Jianli; Xue, Lifen; Yang, Chenhao; Luo, Yixiao; Shi, Haishui; Lu, Lin

2012-01-01

Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA), but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC). We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

The three-loop splitting functions Pqg(2 and Pgg(2,NF

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J. Ablinger

2017-09-01

Full Text Available We calculate the unpolarized twist-2 three-loop splitting functions Pqg(2(x and Pgg(2,NF(x and the associated anomalous dimensions using massive three-loop operator matrix elements. While we calculate Pgg(2,NF(x directly, Pqg(2(x is computed from 1200 even moments, without any structural prejudice, using a hierarchy of recurrences obtained for the corresponding operator matrix element. The largest recurrence to be solved is of order 12 and degree 191. We confirm results in the foregoing literature.

NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus

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Oikawa Kensuke

2012-07-01

Full Text Available Abstract Background Nuclear factor kappa B (NF-κB is a transcription factor typically expressed with two specific subunits (p50, p65. Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP, a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/− leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM. To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+. Results We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention. Conclusions These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.

Control of NF-kB activity in human melanoma by bromodomain and extra-terminal protein inhibitor I-BET151.

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Gallagher, Stuart J; Mijatov, Branka; Gunatilake, Dilini; Gowrishankar, Kavitha; Tiffen, Jessamy; James, Wilmott; Jin, Lei; Pupo, Gulietta; Cullinane, Carleen; McArthur, Grant A; Tummino, Peter J; Rizos, Helen; Hersey, Peter

2014-11-01

The transcription factor NF-kappaB (NF-kB) is a key regulator of cytokine and chemokine production in melanoma and is responsible for symptoms such as anorexia, fatigue, and weight loss. In addition, NF-kB is believed to contribute to progression of the disease by upregulation of cell cycle and anti-apoptotic genes and to contribute to resistance against targeted therapies and immunotherapy. In this study, we have examined the ability of the bromodomain and extra-terminal (BET) protein inhibitor I-BET151 to inhibit NF-kB in melanoma cells. We show that I-BET151 is a potent, selective inhibitor of a number of NF-kB target genes involved in induction of inflammation and cell cycle regulation and downregulates production of cytokines such as IL-6 and IL-8. SiRNA studies indicate that BRD2 is the main BET protein involved in regulation of NF-kB and that I-BET151 caused transcriptional downregulation of the NF-kB subunit p105/p50. These results suggest that BET inhibitors may have an important role in treatment of melanoma where activation of NF-kB may have a key pathogenic role. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhibitory effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation

International Nuclear Information System (INIS)

Shi Jianhui; Niu Yuhong; Ge Junbo; Xu Xiaoping; Cheng Wenying; Feng Xiao; Zhang Zongliang

2002-01-01

Objective: To explore effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation. Methods: Apoptosis in P388 cells induced by radiation treatment was detected by TUNEL assay. EMSA was used to detect the activation of NF-κB . Results: The apoptosis and activation of NF-κB in P388 cells could be induced by radiation. Dexamethasone (DXM) which could suppress activation of NF-κB of P388 cells increased significantly the apoptosis induced by radiation. Apoptosis rates in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure increased by 60%, 100%, 129% and 67%, respectively. Activation rates of NF-κB in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure decreased by 25%, 45%, 52% and 40%, respectively. Conclusion: Radiation induces apoptosis and activation of NF-κB in P388 cells simultaneously. Glucocorticoid enhances apoptosis in leukemic cells, which may be by means of suppressing activation of NF-κB

Reciprocal Regulation of NF-kB (Relish) and Subolesin in the Tick Vector, Ixodes scapularis

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Galindo, Ruth C.; Kocan, Katherine M.; Blouin, Edmour F.; Mitra, Ruchira; Alberdi, Pilar; Villar, Margarita; de la Fuente, José

2013-01-01

Background Tick Subolesin and its ortholog in insects and vertebrates, Akirin, have been suggested to play a role in the immune response through regulation of nuclear factor-kappa B (NF-kB)-dependent and independent gene expression via interaction with intermediate proteins that interact with NF-kB and other regulatory proteins, bind DNA or remodel chromatin to regulate gene expression. The objective of this study was to characterize the structure and regulation of subolesin in Ixodes scapularis. I. scapularis is a vector of emerging pathogens such as Borrelia burgdorferi, Anaplasma phagocytophilum and Babesia microti that cause in humans Lyme disease, anaplasmosis and babesiosis, respectively. The genome of I. scapularis was recently sequenced, and this tick serves as a model organism for the study of vector-host-pathogen interactions. However, basic biological questions such as gene organization and regulation are largely unknown in ticks and other arthropod vectors. Principal Findings The results presented here provide evidence that subolesin/akirin are evolutionarily conserved at several levels (primary sequence, gene organization and function), thus supporting their crucial biological function in metazoans. These results showed that NF-kB (Relish) is involved in the regulation of subolesin expression in ticks, suggesting that as in other organisms, different NF-kB integral subunits and/or unknown interacting proteins regulate the specificity of the NF-kB-mediated gene expression. These results suggested a regulatory network involving cross-regulation between NF-kB (Relish) and Subolesin and Subolesin auto-regulation with possible implications in tick immune response to bacterial infection. Significance These results advance our understanding of gene organization and regulation in I. scapularis and have important implications for arthropod vectors genetics and immunology highlighting the possible role of NF-kB and Subolesin/Akirin in vector

TXNIP/TRX/NF-κB and MAPK/NF-κB pathways involved in the cardiotoxicity induced by Venenum Bufonis in rats.

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Bi, Qi-Rui; Hou, Jin-Jun; Qi, Peng; Ma, Chun-Hua; Feng, Rui-Hong; Yan, Bing-Peng; Wang, Jian-Wei; Shi, Xiao-Jian; Zheng, Yuan-Yuan; Wu, Wan-Ying; Guo, De-An

2016-03-10

Venenum Bufonis (VB) is a widely used traditional medicine with serious cardiotoxic effects. The inflammatory response has been studied to clarify the mechanism of the cardiotoxicity induced by VB for the first time. In the present study, Sprague Dawley (SD) rats, were administered VB (100, 200, and 400 mg/kg) intragastrically, experienced disturbed ECGs (lowered heart rate and elevated ST-segment), increased levels of serum indicators (creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and serum interleukin (IL-6, IL-1β, TNF-α) at 2 h, 4 h, 6 h, 8 h, 24 h, and 48 h, which reflected that an inflammatory response, together with cardiotoxicity, were involved in VB-treated rats. In addition, the elevated serum level of MDA and the down-regulated SOD, CAT, GSH, and GPx levels indicated the appearance of oxidative stress in the VB-treated group. Furthermore, based on the enhanced expression levels of TXNIP, p-NF-κBp65, p-IκBα, p-IKKα, p-IKKβ, p-ERK, p-JNK, and p-P38 and the obvious myocardial degeneration, it is proposed that VB-induced cardiotoxicity may promote an inflammatory response through the TXNIP/TRX/NF-κB and MAPK/NF-κB pathways. The observed inflammatory mechanism induced by VB may provide a theoretical reference for the toxic effects and clinical application of VB.

Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

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Tao Zhu

Full Text Available Nuclear factor-κB (NF-κB is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro.In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro.These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Andrographolide Protects against LPS-Induced Acute Lung Injury by Inactivation of NF-κB

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Zhu, Tao; Wang, Dao-xin; Zhang, Wei; Liao, Xiu-qing; Guan, Xian; Bo, Hong; Sun, Jia-yang; Huang, Ni-wen; He, Jing; Zhang, Yun-kun; Tong, Jing; Li, Chang-yi

2013-01-01

Background Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. Methods and Results In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. Conclusions These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI. PMID:23437127

NF-κB Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death.

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Kumar, Amrendra; Gordy, Laura E; Bezbradica, Jelena S; Stanic, Aleksandar K; Hill, Timothy M; Boothby, Mark R; Van Kaer, Luc; Joyce, Sebastian

2017-11-15

Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-x L -coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas.

Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway.

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Ren, Ke; Zhang, Wei; Shi, Yujun; Gong, Jianping

2010-06-01

Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissues. Pim-2 level was increased in L02 cells after the transfection of Pim-2 gene, but decreased in HepG2 cells after the transfection of Pim-2 SiRNA. The levels of NF-kappaB and API-5, as well as NF-kappaB activity and API-5 phosphorylation level, were in accordance with Pim-2 level, but could be reversed by Parthenolide. Cell apoptosis rates were negatively correlated with API-5 phosphorylation level. Therefore, we infer that Pim-2 could activate API-5 to inhibit the apoptosis of liver cells, and NF-kappaB is the key regulator.

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

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Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-κB and Akt pathways

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Wang Xia; Chen Wenshu; Lin Yong

2007-01-01

Blockage of either nuclear factor-κB (NF-κB) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-κB activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-κB. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-κB activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-κB activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-κB and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-κB and Akt, which may be applied in lung cancer therapy

Regorafenib induces extrinsic and intrinsic apoptosis through inhibition of ERK/NF-κB activation in hepatocellular carcinoma cells.

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Tsai, Jai-Jen; Pan, Po-Jung; Hsu, Fei-Ting

2017-02-01

The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

Fish oil suppresses cell growth and metastatic potential by regulating PTEN and NF-κB signaling in colorectal cancer.

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Shevali Kansal

Full Text Available Homeostasis in eukaryotic tissues is tightly regulated by an intricate balance of the prosurvival and antisurvival signals. The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10, a dual-specificity phosphatase, plays a functional role in cell cycle arrest and apoptosis. NF-κB and its downstream regulators (such as VEGF play a central role in prevention of apoptosis, promotion of inflammation and tumor growth. Therefore, we thought to estimate the expression of PTEN, Poly-ADP-ribose polymerase (PARP, NF-κBp50, NF-κBp65 and VEGF to evaluate the effect of supplementation of fish oil on apoptotic and inflammatory signaling in colon carcinoma. Male wistar rats in Group I received purified diet while Group II and III received modified diet supplemented with FO∶CO(1∶1&FO∶CO(2.5∶1 respectively. These were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and that sacrificed after 16 weeks constituted post-initiation phase. We have analysed expression of PTEN, NF-κBp50, NF-κBp65 by flowcytometer and nuclear localization of NF-κB by immunofluorescence. PARP and VEGF were assessed by immunohistochemistry. In the initiation phase, animals receiving DMH have shown increased % of apoptotic cells, PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF however in post-initiation phase no significant alteration in apoptosis with decreased PTEN and increased PARP, NF-κBp50, NF-κBp65 and VEGF were observed as compared to control animals. On treatment with both ratios of fish oil in both the phases, augmentation in % of apoptotic cells, decreased PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF were documented with respect to DMH treated animals with effect being more exerted with higher ration in post-initiation phase. Hence, fish oil activates

In Vivo Zonal Variation and Liver Cell-Type Specific NF-κB Localization after Chronic Adaptation to Ethanol and following Partial Hepatectomy.

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Harshavardhan Nilakantan

Full Text Available NF-κB is a major inflammatory response mediator in the liver, playing a key role in the pathogenesis of alcoholic liver injury. We investigated zonal as well as liver cell type-specific distribution of NF-κB activation across the liver acinus following adaptation to chronic ethanol intake and 70% partial hepatectomy (PHx. We employed immunofluorescence staining, digital image analysis and statistical distributional analysis to quantify subcellular localization of NF-κB in hepatocytes and hepatic stellate cells (HSCs. We detected significant spatial heterogeneity of NF-κB expression and cellular localization between cytoplasm and nucleus across liver tissue. Our main aims involved investigating the zonal bias in NF-κB localization and determining to what extent chronic ethanol intake affects this zonal bias with in hepatocytes at baseline and post-PHx. Hepatocytes in the periportal area showed higher NF-κB expression than in the pericentral region in the carbohydrate-fed controls, but not in the ethanol group. However, the distribution of NF-κB nuclear localization in hepatocytes was shifted towards higher levels in pericentral region than in periportal area, across all treatment conditions. Chronic ethanol intake shifted the NF-κB distribution towards higher nuclear fraction in hepatocytes as compared to the pair-fed control group. Ethanol also stimulated higher NF-κB expression in a subpopulation of HSCs. In the control group, PHx elicited a shift towards higher NF-κB nuclear fraction in hepatocytes. However, this distribution remained unchanged in the ethanol group post-PHx. HSCs showed a lower NF-κB expression following PHx in both ethanol and control groups. We conclude that adaptation to chronic ethanol intake attenuates the liver zonal variation in NF-κB expression and limits the PHx-induced NF-κB activation in hepatocytes, but does not alter the NF-κB expression changes in HSCs in response to PHx. Our findings provide new

Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans.

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Vázquez-Agell, M; Urpi-Sarda, M; Sacanella, E; Camino-López, S; Chiva-Blanch, G; Llorente-Cortés, V; Tobias, E; Roura, E; Andres-Lacueva, C; Lamuela-Raventós, R M; Badimon, L; Estruch, R

2013-03-01

Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis. The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions, although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered. Nuclear factor κB (NF-κB) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM) and cytokine expression and its activation is the first step in triggering the inflammatory process. The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM. Eighteen healthy volunteers randomly received 3 interventions: 40g of cocoa powder with milk (CM), with water (CW), and only milk (M). NF-κB activation in leukocytes and AM (sICAM, sVCAM, E-selectin) were measured before and 6h after each intervention. Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM (P cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health. Copyright © 2011 Elsevier B.V. All rights reserved.

Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

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Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

2006-07-01

Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

Mechanism by which nuclear factor-kappa beta (NF-kB regulates ovine fetal pulmonary vascular smooth muscle cell proliferation

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Uchenna D. Ogbozor

2015-09-01

Full Text Available Platelet activating factor (PAF modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR in pulmonary vascular smooth muscle cells (PVSMC to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a PAF induces NF-kB p65 DNA binding and (b NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

Mechanism by which nuclear factor-kappa beta (NF-kB) regulates ovine fetal pulmonary vascular smooth muscle cell proliferation.

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Ogbozor, Uchenna D; Opene, Michael; Renteria, Lissette S; McBride, Shaemion; Ibe, Basil O

2015-09-01

Platelet activating factor (PAF) modulates ovine fetal pulmonary hemodynamic. PAF acts through its receptors (PAFR) in pulmonary vascular smooth muscle cells (PVSMC) to phosphorylate and induce nuclear translocation of NF-kB p65 leading to PVSMC proliferation. However, the interaction of NF-kB p65 and PAF in the nuclear domain to effect PVSMC cell growth is not clearly defined. We used siRNA-dependent translation initiation arrest to study a mechanism by which NF-kB p65 regulates PAF stimulation of PVSMC proliferation. Our hypotheses are: (a) PAF induces NF-kB p65 DNA binding and (b) NF-kB p65 siRNA attenuates PAF stimulation of PVSMC proliferation. For DNA binding, cells were fed 10 nM PAF with and without PAFR antagonists WEB 2170, CV 3988 or BN 52021 and incubated for 12 h. DNA binding was measured by specific ELISA. For NF-kB p65 siRNA effect, starved cells transfected with the siRNA were incubated for 24 h with and without 10 nM PAF. Cell proliferation was measured by DNA synthesis while expression of NF-kB p65 and PAFR protein was measured by Western blotting. In both studies, the effect of 10% FBS alone was used as the positive control. In general, PAF stimulated DNA binding which was inhibited by PAFR antagonists. siRNAs to NF-kB p65 and PAFR significantly attenuated cell proliferation compared to 10% FBS and PAF effect. Inclusion of PAF in siRNA-treated cells did not reverse inhibitory effect of NF-kB p65 siRNA on DNA synthesis. PAFR expression was inhibited in siRNA-treated cells. These data show that PAF-stimulation of PVSMC proliferation occurs via a PAFR-NF-kB p65 linked pathway.

Rac1 controls Schwann cell myelination through cAMP and NF2/merlin

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Guo, Li; Moon, Chandra; Niehaus, Karen; Zheng, Yi; Ratner, Nancy

2013-01-01

During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo, and the shortened processes in cultured Rac1-CKO SCs in vitro. Mechanistically, cyclic adenosine monophosphate (cAMP) levels and E-cadherin expression were decreased in the absence of Rac1, and both were restored by mutation of NF2/merlin. Reduced cAMP is a cause of the myelin deficiency in Rac1-CKO mice, as elevation of cAMP by rolipram in Rac1-CKO mice in vivo allowed myelin formation. Thus NF2/merlin and cAMP function downstream of Rac1 signaling in SC myelination, and cAMP levels control Rac1-regulated SC myelination. PMID:23197717

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

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Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Activation of NF-κB in basolateral amygdala is required for memory reconsolidation in auditory fear conditioning.

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Jijian Si

Full Text Available Posttraumatic stress disorder (PTSD is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA, but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC. We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

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Quan, Juan-Hua; Kang, Byung-Hun; Yang, Jung-Bo; Rhee, Yun-Ee; Noh, Heung-Tae; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min

2017-01-01

Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS), and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5) for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC), reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway. PMID:29410962

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

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Juan-Hua Quan

2017-01-01

Full Text Available Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS, and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5 for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC, reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway.

In silico analysis of compounds characterized from ethanolic extract of Cucurbita pepo with NF-κB-inhibitory potential

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Solomon O. Rotimi

2014-12-01

Full Text Available NF-κB controls cellular growth properties of cells and its regulation is key to the management of disease like cancer. Although plant-derived bioactives have been reported to inhibit NF-κB, there is limited knowledge on the interactions between the phytochemicals and NF-κB. In this study, we identified the phytochemicals in ethanolic extract of Cucurbita pepo using Gas Chromatography-Mass Spectroscopy technique and used in silico approach to understand the interaction between the identified phytochemicals and NF-κB using Molegro Virtual Docker. The docking algorithm showed that nine phytochemicals fit well into the pocket on NF-κB. Our analysis showed that Lys144 is a prominent residue by involving in the binding of 9-octadecenoic acid (Z-, methyl ester, hexadecanoic acid, methyl ester and octadecanoic acid, methyl ester with the moldock score of -55.5264, -57.4634 and -61.1258 respectively. Hence, the binding of these phytochemicals to NF-κB could be responsible for the anti-inflammatory and anti-cancer property of C. pepo.

Adaptive evolution of relish, a Drosophila NF-kappaB/IkappaB protein.

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Begun, D J; Whitley, P

2000-01-01

NF-kappaB and IkappaB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-kappaB/IkappaB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appear...

Social and Emotional Functioning of Children with NF-1 and Their Families: A Case Controlled Study

National Research Council Canada - National Science Library

Noll, Robert

2000-01-01

...) of children with NF and explore potential linkages between NF and QOL in these 3 domains. The second objective of this work is to evaluate parental distress, family functioning, and child rearing practices...

Social and Emotional Functioning of Children With NF-1 and Their Families; A Case Controlled Study

National Research Council Canada - National Science Library

Noll, Robert

2001-01-01

...) of children with NF and explore potential linkages between NF and QOL in these 3 domains. The second objective of this work is to evaluate parental distress, family functioning, and child rearing practices...

NF1, Sp1 and HSF1 are synergistically involved in sulfide-induced sqr activation in echiuran worm Urechis unicinctus

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaolong; Qin, Zhenkui; Li, Xueyu; Ma, Xiaoyu; Gao, Beibei; Zhang, Zhifeng, E-mail: zzfp107@ouc.edu.cn

2016-06-15

Highlights: • Sulfide activates sqr transcription against respiratory toxicity in Urechis unicinctus. • Sulfide increases expressions and activities of NF1, Sp1 and HSF1 in a time-dependent manner. • NF1 and Sp1 participate in both basal and early sulfide-induced sqr transcription. • HSF1 functions more significantly than NF1 and Sp1 in sulfide-induced sqr transcription. • Transcription factors NF1, Sp1 and HSF1 enhance sqr promoter activity synergistically. - Abstract: Background: Sulfide is a well-known environmental toxic substance. Mitochondrial sulfide oxidation is a main mechanism of sulfide detoxification in organisms, and sulfide: quinone oxidoreductase (SQR) is a key enzyme which is involved in transferring electrons from sulfide to ubiquinone and converting sulfide into thiosulfate. Previous studies have revealed the SQR-mediated mitochondrial sulfide oxidation exists in the echiuran worm Urechis unicinctus, and its sqr mRNA level increased significantly when the worm is exposed to sulfide. In this study, we attempt to reveal the synergistic regulation of transcription factors on sulfide-induced sqr transcription in U. unicinctus. Methods: ChIP and EMSA were used to identify the interactions between sqr proximal promoter (from −391 to +194 bp) and transcription factors NF1 (nuclear factor 1) and Sp1 (specificity protein 1). Site-directed mutation and transfection assays further revealed their binding sites and synergistic roles of HSF1, NF1 and Sp1 in the sqr transcription. When U. unicinctus were exposed to 150 μM sulfide, the expression levels and nuclear contents of NF1 and Sp1 were examined by Western blotting, and the binding contents between NF1 or Sp1 and the sqr promoter were also detected by ChIP. Results: Transcription factors NF1 and Sp1 were confirmed to interact with the sqr proximal promoter, and their binding sites were identified in −75 to −69 bp for NF1 and −210 to −201 bp for Sp1. Transfection assays showed mutation

Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo.

Science.gov (United States)

Ingram, D A; Yang, F C; Travers, J B; Wenning, M J; Hiatt, K; New, S; Hood, A; Shannon, K; Williams, D A; Clapp, D W

2000-01-03

Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's "two hit" model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W(41) mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras-mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W(41)) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.

Genetic analyses of the NF1 gene in Turkish neurofibromatosis type I patients and definition of three novel variants

Directory of Open Access Journals (Sweden)

Ulusal SD

2017-06-01

Full Text Available Neurofibromatosis Type I (NF1 is a multi systemic autosomal dominant neurocutaneous disorder predisposing patients to have benign and/or malignant lesions predominantly of the skin, nervous system and bone. Loss of function mutations or deletions of the NF1 gene is responsible for NF1 disease. Involvement of various pathogenic variants, the size of the gene and presence of pseudogenes makes it difficult to analyze. We aimed to report the results of 2 years of multiplex ligation-dependent probe amplification (MLPA and next generation sequencing (NGS for genetic diagnosis of NF1 applied at our genetic diagnosis center. The MLPA, semiconductor sequencing and Sanger sequencing were performed in genomic DNA samples from 24 unrelated patients and their affected family members referred to our center suspected of having NF1. In total, three novel and 12 known pathogenic variants and a whole gene deletion were determined. We suggest that next generation sequencing is a practical tool for genetic analysis of NF1. Deletion/duplication analysis with MLPA may also be helpful for patients clinically diagnosed to carry NF1 but do not have a detectable mutation in NGS.

Inhibition of NF-κB by a cell permeable form of IκBα induces apoptosis in eosinophils

International Nuclear Information System (INIS)

Fujihara, Satoko; Jaffray, Ellis; Farrow, Stuart N.; Rossi, Adriano G.; Haslett, Christopher; Hay, Ronald T.

2005-01-01

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-κB, we have fused the TAT-peptide to a version of IκBα that is resistant to signal-induced degradation. TAT-IκBα(S32A, S36A) inhibited NF-κB-dependent transcription in HeLa and A549 cells by retaining NF-κB p65 in the cytoplasm. Introduction of TAT-IκBα(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-κB and induced apoptosis. Thus, continuous NF-κB-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells

Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

Energy Technology Data Exchange (ETDEWEB)

Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

Collagen gel protects L929 cells from TNFα-induced death by activating NF-κB.

Science.gov (United States)

Wang, Hong-Ju; Li, Meng-Qi; Liu, Wei-Wei; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2017-09-01

Type I collagen is one of the most abundant components of extracellular matrix. We previously illustrated that murine fibrosarcoma L929 cells grew well on type I collagen gel and escaped from TNFα-induced cell death. In this study, we investigated the mechanism underlying the protective effect of collagen gel. We used western blot, confocal microscopy, MTT assay and flow cytometry by introducing fluorescence staining to determine the expression levels of nuclear factor kappa B (NF-κB), inhibitory ratio and autophagy. L929 cells on collagen gel showed higher expression of NF-κB in the nucleus. Inhibition of NF-κB with pyrrolidine dithiocarbamate hydrochloride (PDTC) or knockdown by NF-κB-siRNA canceled the protective effect of collagen gel on L929 cells from TNFα-induced death, suggesting for the role of NF-κB in the protection from cell death. We found a new aspect of the effect of PDTC on L929 cells cultured on collagen gel. PDTC alone without TNFα induced apoptosis in the L929 cells cultured on collagen gel but not the cells on plastic dish. The apoptosis induction of the L929 cells cultured on collagen gel with PDTC was repressed by inhibiting autophagy with chloroquine, an autophagy inhibitor, suggesting that autophagy contributes to the death induced by the treatment with PDTC. Possible underlying mechanism of this finding is discussed. NF-κB played an important role in protecting the L929 cells cultured on collagen gel from TNFα-induced death.

p38 mitogen-activated protein kinase up-regulates NF-κB transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

International Nuclear Information System (INIS)

Ji, Guoping; Liu, Dongxu; Liu, Jing; Gao, Hui; Yuan, Xiao; Shen, Gang

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-κB in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-κB activation during myogenesis, not through down-regulation of degradation of IκB-α, and consequent translocation of the p65 subunit of NF-κB to the nucleus. It is likely that stretch-induced NF-κB activation by phosphorylation of p65 NF-κB. Moreover, depletion of p38α using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-κB activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-κB signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The α isoform of p38MAP kinase regulates the transcriptional activation of NF-κB following stimulation with cyclic stretch.

p38 mitogen-activated protein kinase up-regulates NF-{kappa}B transcriptional activation through RelA phosphorylation during stretch-induced myogenesis

Energy Technology Data Exchange (ETDEWEB)

Ji, Guoping [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China); Liu, Dongxu [Department of Orthodontics, College of Stomatology, Shandong University, Jinan, Shandong Province 250012 (China); Liu, Jing [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Gao, Hui [Department of Orthodontics, Tianjin Stomatological Hospital, Tianjin 300041 (China); Yuan, Xiao, E-mail: yuanxiaoqd@163.com [Department of Orthodontics, The Affiliated Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong Province 266075 (China); Shen, Gang, E-mail: ganshen2007@163.com [Department of Orthodontics, College of Stomatology, Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Research Institute of Stomatology, Shanghai 200011 (China)

2010-01-01

p38 MAPK and nuclear factor-B (NF-B) signaling pathways play an indispensable role in the control of skeletal myogenesis. The specific contribution of these signaling pathways to the response of myoblast to the mechanical stimulation and the molecular mechanisms underlying this response remain unresolved. Using an established in vitro model, we now show that p38 MAP kinase activity regulates the transcriptional activation of NF-{kappa}B in response to mechanical stimulation of myoblasts. Furthermore, SB203580 blocked stretch-induced NF-{kappa}B activation during myogenesis, not through down-regulation of degradation of I{kappa}B-{alpha}, and consequent translocation of the p65 subunit of NF-{kappa}B to the nucleus. It is likely that stretch-induced NF-{kappa}B activation by phosphorylation of p65 NF-{kappa}B. Moreover, depletion of p38{alpha} using siRNA significantly reduces stretch-induced phosphorylation of RelA and NF-{kappa}B activity. These results provides the first evidence of a cross-talk between p38 MAPK and NF-{kappa}B signaling pathways during stretch-induced myogenesis, with phosphorylation of RelA being one of the effectors of this promyogenic mechanism. The {alpha} isoform of p38MAP kinase regulates the transcriptional activation of NF-{kappa}B following stimulation with cyclic stretch.

Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance

NARCIS (Netherlands)

Beek, M.H. van; Oravecz-Wilson, K.I.; Delekta, P.C.; Gu, S.; Li, X.; Jin, X.; Apel, I.J.; Konkle, K.S.; Feng, Y.; Teitelbaum, D.H.; Ruland, J.; McAllister-Lucas, L.M.; Lucas, P.C.

2012-01-01

Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear. Here,

Do hormonal contraceptives stimulate growth of neurofibromas? A survey on 59 NF1 patients

International Nuclear Information System (INIS)

Lammert, Marge; Mautner, Victor-Felix; Kluwe, Lan

2005-01-01

Neurofibromas are benign tumors of the peripheral nerves and hallmark of neurofibromatosis type 1 (NF1), a tumor suppressor gene syndrome. Neurofibromas mostly start developing at puberty and can increase in size and number during pregnancy. Expression of progesterone receptors has been found in 75% of the tumors. Many female NF1 patients are thus concerned about the possibility that hormonal contraceptives may stimulate the growth of their neurofibromas. A survey was carried out on 59 female NF1 patients who are practicing or have practiced hormonal contraception to examine the effect of the various contraceptives on the growth of neurofibromas. Majority (53 out of 58) of patients who received oral estrogen-progestogen or pure progestogen preparations reported no associated tumor growth. In contrast, significant tumor growth was reported by two patients who received depot contraceptive containing high dose of synthetic progesterone. Oral contraceptives do not seem to stimulate the growth of neurofibromas in NF1 patients. High doses of progesterone might stimulate the growth of neurofibromas and deserve more caution

Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

Directory of Open Access Journals (Sweden)

Ashidha Gopal

Full Text Available Shigella dysenteriae (S.dysenteriae the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate β-catenin degradation which in turn decreased the association between NF-κB and β-catenin. Also, we showed that S.dysenteriae infection increased GSK-3β kinase activity which in turn phosphorylates β-catenin for its degradation by ubiquitination and upregulates IL-8 through NF-κB activation thereby leading to inflammation. Thus these findings revealed the role of β-catenin/ NF-κB and GSK-3β in modulating the inflammatory response during bacterial infection and also showed that β-catenin acts as a critical regulator of inflammation.

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

International Nuclear Information System (INIS)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena

2017-01-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by 60 Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found to be

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by {sup 60}Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found

Insulin receptor substrate-3, interacting with Bcl-3, enhances p50 NF-{kappa}B activity

Energy Technology Data Exchange (ETDEWEB)

Kabuta, Tomohiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Hakuno, Fumihiko; Cho, Yoshitake; Yamanaka, Daisuke; Chida, Kazuhiro [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan); Asano, Tomoichiro [Graduate School of Biomedical Science, Hiroshima University, Hiroshima 734-8551 (Japan); Wada, Keiji [Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502 (Japan); Takahashi, Shin-Ichiro, E-mail: atkshin@mail.ecc.u-tokyo.ac.jp [Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657 (Japan)

2010-04-09

The insulin receptor substrate (IRS) proteins are major substrates of both insulin receptor and insulin-like growth factor (IGF)-I receptor tyrosine kinases. Previously, we reported that IRS-3 is localized to both cytosol and nucleus, and possesses transcriptional activity. In the present study, we identified Bcl-3 as a novel binding protein to IRS-3. Bcl-3 is a nuclear protein, which forms a complex with the homodimer of p50 NF-{kappa}B, leading to enhancement of transcription through p50 NF-{kappa}B. We found that Bcl-3 interacts with the pleckstrin homology domain and the phosphotyrosine binding domain of IRS-3, and that IRS-3 interacts with the ankyrin repeat domain of Bcl-3. In addition, IRS-3 augmented the binding activity of p50 to the NF-{kappa}B DNA binding site, as well as the tumor necrosis factor (TNF)-{alpha}-induced transcriptional activity of NF-{kappa}B. Lastly, IRS-3 enhanced NF-{kappa}B-dependent anti-apoptotic gene induction and consequently inhibited TNF-{alpha}-induced cell death. This series of results proposes a novel function for IRS-3 as a transcriptional regulator in TNF-{alpha} signaling, distinct from its function as a substrate of insulin/IGF receptor kinases.

Akt-dependent NF-κB activation is required for bile acids to rescue colon cancer cells from stress-induced apoptosis

International Nuclear Information System (INIS)

Shant, Jasleen; Cheng, Kunrong; Marasa, Bernard S.; Wang Jianying; Raufman, Jean-Pierre

2009-01-01

Conjugated secondary bile acids promote human colon cancer cell proliferation by activating EGF receptors (EGFR). We hypothesized that bile acid-induced EGFR activation also mediates cell survival by downstream Akt-regulated activation of NF-κB. Deoxycholyltaurine (DCT) treatment attenuated TNF-α-induced colon cancer cell apoptosis, and stimulated rapid and sustained NF-κB nuclear translocation and transcriptional activity (detected by NF-κB binding to an oligonucleotide consensus sequence and by activation of luciferase reporter gene constructs). Both DCT-induced NF-κB nuclear translocation and attenuation of TNF-α-stimulated apoptosis were dependent on EGFR activation. Inhibitors of nuclear translocation, proteosome activity, and IκBα kinase attenuated NF-κB transcriptional activity. Cell transfection with adenoviral vectors encoding a non-degradable IκBα 'super-repressor' blocked the actions of DCT on both NF-κB activation and TNF-α-induced apoptosis. Likewise, transfection with mutant akt and treatment with a chemical inhibitor of Akt attenuated effects of DCT on NF-κB transcriptional activity and TNF-α-induced apoptosis. Chemical inhibitors of Akt and NF-κB activation also attenuated DCT-induced rescue of H508 cells from ultraviolet radiation-induced apoptosis. Collectively, these observations indicate that, downstream of EGFR, bile acid-induced colon cancer cell survival is mediated by Akt-dependent NF-κB activation. These findings provide a mechanism whereby bile acids increase resistance of colon cancer to chemotherapy and radiation

Regulation of development and function of different T cell subtypes by Rel/NF-κB family members

International Nuclear Information System (INIS)

Vallabhapurapu, S.

2004-09-01

This study reveals the requirement of distinct members of the Rel/NF-κB family in both hematopoietic and non-hematopoietic cells for the development of thymic NKT cells. Activation of NF-κB via the classical IκBα-regulated pathway is required within the NKT precursors for their efficient maturation from NK1.1 - precursors to mature NK1.1 + NKT cells. The Rel/NF-κB family member RelB, on the other hand, is required in thymic stromal cells for the generation of very early NK1.1 - precursors. NF-κB-inducing kinase (NIK) has also been shown to be required in thymic stromal cells for NKT cell development and this study demonstrates that NIK specifically regulates both constitutive and signal-induced DNA binding of RelB, but not RelA. Moreover, NIK-induced DNA binding of RelB depends on the processing of inhibitory p100 to p52, revealing an alternate pathway of NF-κB induction. Thus, Rel/NF-κB complexes activated by the classical IκBα-regulated pathway in NKT precursors and an alternate NIK/p100/RelB pathway in thymic stromal cells regulate different stages of NKT cell development. (orig.)

Regulation of development and function of different T cell subtypes by Rel/NF-{kappa}B family members

Energy Technology Data Exchange (ETDEWEB)

Vallabhapurapu, S.

2004-09-01

This study reveals the requirement of distinct members of the Rel/NF-{kappa}B family in both hematopoietic and non-hematopoietic cells for the development of thymic NKT cells. Activation of NF-{kappa}B via the classical I{kappa}B{alpha}-regulated pathway is required within the NKT precursors for their efficient maturation from NK1.1{sup -} precursors to mature NK1.1{sup +} NKT cells. The Rel/NF-{kappa}B family member RelB, on the other hand, is required in thymic stromal cells for the generation of very early NK1.1{sup -} precursors. NF-{kappa}B-inducing kinase (NIK) has also been shown to be required in thymic stromal cells for NKT cell development and this study demonstrates that NIK specifically regulates both constitutive and signal-induced DNA binding of RelB, but not RelA. Moreover, NIK-induced DNA binding of RelB depends on the processing of inhibitory p100 to p52, revealing an alternate pathway of NF-{kappa}B induction. Thus, Rel/NF-{kappa}B complexes activated by the classical I{kappa}B{alpha}-regulated pathway in NKT precursors and an alternate NIK/p100/RelB pathway in thymic stromal cells regulate different stages of NKT cell development. (orig.)

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

International Nuclear Information System (INIS)

Lacoste, J.; Cohen, L.; Hiscott, J.

1991-01-01

The effect of constitutive Tax expression on the interaction of NF-κ B with its recognition sequence and on NF-κ B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-κ B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-κ B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters

FACTOR NUCLEAR kB (NF-kB: SIGNALOSOMA Y SU IMPORTANCIA EN ENFERMEDADES INFLAMATORIAS Y CÁNCER

Directory of Open Access Journals (Sweden)

Nancy P. Echeverry R.L

2008-04-01

Full Text Available El factor nuclear kB (NF-kB es un dímero constituido por proteínas de la familia Rel. El NF-kB se encuentra en el citoplasma unido a proteínas inhibidoras (IkB. Las IkB son fosforiladas por diferentes cinasas que hacen parte del signalosoma como las cinasas de IKKa e IKKb y el modulador esencial de NF-kB (NEMO, la proteína cinasa activadora de mitosis (MAPK o p38 y la cinasa inductora de NF-kB (NIK. Estas cinasas al ser activadas por señales dependientes de citocinas y luz ultravioleta, fosforilan las IkB provocando su ubiquitinación, su degradación por proteosoma y la subsecuente liberación y translocación al núcleo de NF-kB. Recientemente se le ha dado una gran importancia al NF-kB en la vía de señalización desencadenada por estrés oxidativo, estrés genotóxico y daño en el DNA. A diferencia de la vía denominada clásica, en esta ruta ocurre una SUMOilación de NEMO y translocación al núcleo. En el núcleo NEMO interactúa con la proteína de la ataxia telangiectasia mutada (ATM activada en respuesta a modificaciones en la cromatina y daño en el DNA. El complejo ATM/NEMO es translocado al citoplasma donde la ATM fosforila a las IKK llevando a la ubiquitinación y posterior liberación de NF-kB que es translocado al núcleo. NF-kB desencadena procesos de supervivencia incluyendo el aumento de la transcripción de enzimas antioxidantes como la superóxido dismutasa, catalasa y glutatión. Estas enzimas participan en el control de los niveles de especies reactivas de oxígeno en la célula. La sobreactivación de NF-kB se relaciona con inflamación y cáncer. En la actualidad se desarrolla una búsqueda de fármacos que actúen sobre moléculas del signalosoma de NF-kB, no sólo para el manejo de enfermedades inflamatorias sino también para el uso durante el tratamiento de tumores resistentes a radio y quimioterapia.

DMPD: Signaling to NF-kappaB by Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available l Med. 2007 Nov;13(11):460-9. Epub 2007 Oct 29. (.png) (.svg) (.html) (.csml) Show Signaling to NF-kappaB by Toll-like receptors. Pub...medID 18029230 Title Signaling to NF-kappaB by Toll-like receptors. Authors Kawai T

Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy

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Broekgaarden, Mans; Kos, Milan; Jurg, Freek A.; van Beek, Adriaan A.; van Gulik, Thomas M.; Heger, Michal

2015-01-01

Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-κB in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-κB in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells. PMID:26307977

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

Energy Technology Data Exchange (ETDEWEB)

Jackson, Shawn S. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Medical Scientist Training Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Oberley, Christopher [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Hooper, Christopher P. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Grindle, Kreg [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Wuerzberger-Davis, Shelly [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Wolff, Jared [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); and others

2015-02-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO–IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO{sup Y308S} mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. - Highlights: • Withaferin A, a NF-κB inhibitor, disrupts signaling induced NEMO localization, a novel point of inhibition. • NEMO can be localized to distinct signaling foci after treatment with TNF. • ABC-type DLCBL cells can be sensitized to apoptosis after treatment with Withaferin A.

Effects of Qingshen Granules on the Oxidative Stress-NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats.

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Jin, Hua; Wang, Yiping; Wang, Dong; Zhang, Lei

2018-01-01

Background . The activation of NF-kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial-mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on oxidative stress and the activation of NF/kB signaling. Seventy male Sprague-Dawley (SD) rats were randomly divided into a sham group, UUO model group, Qingshen Granules (QSG) high-dose, medium-dose, and low-dose groups, PDTC group, and candesartan group (10 rats in each group). Our study demonstrated that oxidative stress-NF/kB signal pathway contributed to the formation of UUO renal interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative stress-NF/kB signal pathway, reducing inflammation, and improving renal tubular EMT.

RelAp43, a member of the NF-κB family involved in innate immune response against Lyssavirus infection.

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Luco, Sophie; Delmas, Olivier; Vidalain, Pierre-Olivier; Tangy, Frédéric; Weil, Robert; Bourhy, Hervé

2012-01-01

NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.

RelAp43, a member of the NF-κB family involved in innate immune response against Lyssavirus infection.

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Sophie Luco

Full Text Available NF-κB transcription factors are crucial for many cellular processes. NF-κB is activated by viral infections to induce expression of antiviral cytokines. Here, we identified a novel member of the human NF-κB family, denoted RelAp43, the nucleotide sequence of which contains several exons as well as an intron of the RelA gene. RelAp43 is expressed in all cell lines and tissues tested and exhibits all the properties of a NF-κB protein. Although its sequence does not include a transactivation domain, identifying it as a class I member of the NF-κB family, it is able to potentiate RelA-mediated transactivation and stabilize dimers comprising p50. Furthermore, RelAp43 stimulates the expression of HIAP1, IRF1, and IFN-β - three genes involved in cell immunity against viral infection. It is also targeted by the matrix protein of lyssaviruses, the agents of rabies, resulting in an inhibition of the NF-κB pathway. Taken together, our data provide the description of a novel functional member of the NF-κB family, which plays a key role in the induction of anti-viral innate immune response.

NF-κB involvement in hyperoxia-induced myocardial damage in newborn rat hearts.

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Zara, Susi; De Colli, Marianna; Rapino, Monica; Di Valerio, Valentina; Marconi, Guya Diletta; Cataldi, Amelia; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

2013-11-01

Premature newborns are frequently exposed to hyperoxia ventilation and some literature data indicate the possibility of hyperoxia-induced myocardial damage. Since nuclear factor κB (NF-κB) is a crucial signaling molecule involved in physiological response to hyperoxia in different cell types as well as in various tissues, our attention has been focused on the role played by NF-κB pathway in response to moderate and severe hyperoxia exposure in rat neonatal heart tissue. Akt and IκBα levels, involved in NF-κB activation, along with the balance between apoptotic and survival pathways have also been investigated. Experimental design of the study has involved exposure of newborn rats to room air (controls), 60 % O2 (moderate hyperoxia), or 95 % O2 (severe hyperoxia) for the first two postnatal weeks. Morphological analysis shows a less compact tissue in rat heart exposed to moderate hyperoxia and a decreased number of nuclei in samples exposed to severe hyperoxia. A significant increase of NF-κB positive nuclei percentage and p-IκBα expression in samples exposed to 95 % hyperoxia compared to control and to 60 % hyperoxia is evidenced; in parallel, an increase of pAkt/Akt ratio in both samples exposed to 95 and 60 % hyperoxia is shown. Furthermore, a more evident cytochrome c/Apaf-1 immunocomplex and a decreased Bcl2 expression in 95 % hyperoxia-exposed sample compared to 60 % exposed one is evidenced. In conclusion, our findings suggest the involvement of the NF-κB pathway and Akt signaling in the mechanisms of myocardial hyperoxic damage in the newborns, with particular reference to the induction of oxidative stress-related apoptosis.

Proteomic Analysis of Brain Protein Expression Levels in NF-κβ p50 -/- Homozygous Knockout Mice

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Owen, Joshua B.; Opii, Wycliffe. O.; Ramassamy, Charles; Pierce, William. M.; Butterfield, D. Allan

2008-01-01

The role of nuclear factor kappa B (NF-κB) in oxidative stress, and most recently in pro- and anti-apoptotic related mechanistic pathways, has well been established. Because of the dual nature of NF-κB, the wide range of genes it regulates and the plethora of stimuli that activate it, various studies addressing the functional role of NF-κB proteins have resulted in a number of differing findings. The present study examined the effect of a stimulus-free environment on the frontal cortex of mic...

Single-cell and population NF-κB dynamic responses depend on lipopolysaccharide preparation.

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Miriam V Gutschow

Full Text Available Lipopolysaccharide (LPS, found in the outer membrane of gram-negative bacteria, elicits a strong response from the transcription factor family Nuclear factor (NF-κB via Toll-like receptor (TLR 4. The cellular response to lipopolysaccharide varies depending on the source and preparation of the ligand, however. Our goal was to compare single-cell NF-κB dynamics across multiple sources and concentrations of LPS.Using live-cell fluorescence microscopy, we determined the NF-κB activation dynamics of hundreds of single cells expressing a p65-dsRed fusion protein. We used computational image analysis to measure the nuclear localization of the fusion protein in the cells over time. The concentration range spanned up to nine orders of magnitude for three E. coli LPS preparations. We find that the LPS preparations induce markedly different responses, even accounting for potency differences. We also find that the ability of soluble TNF receptor to affect NF-κB dynamics varies strikingly across the three preparations.Our work strongly suggests that the cellular response to LPS is highly sensitive to the source and preparation of the ligand. We therefore caution that conclusions drawn from experiments using one preparation may not be applicable to LPS in general.

A complex relationship between TRAF3 and non-canonical NF-κB2 activation in B lymphocytes

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Wai Wai Lin

2013-12-01

Full Text Available The adaptor protein TRAF3 restrains BAFF receptor (BAFFR and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss- of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM. It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-B inducing kinase NIK, and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss of function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-B2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation and NF-B2 activation.

Elaboração e Caracterização de cookie com adição de farinha do mesocarpo do fruto do Marizeiro (Geoffroea spinosa

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Jaciara D. Costa

2015-04-01

Full Text Available O Marizeiro (Geoffroea spinosa é uma planta originária do bioma Caatinga, vegetação características da Região Nordeste do Brasil, que já fora considerada uma boa fonte de alimento. O fruto do Marizeiro, Mari, possui boas fontes de proteínas e açucares e baixo teor de lipídios. Por suas características nutricionais, a farinha do mesocarpo do Mari desponta como ingrediente alimentar altamente desejável para enriquecer outros alimentos. O objetivo do nosso trabalho foi obter um biscoito tipo cookie enriquecido com a farinha do mesocarpo do fruto do Mari, avaliar suas características físico-químicas e microbiológicas. Os dados da caracterização físico-químico revelaram excelentes níveis proteicos para as amostras F2 com 5% e F3 com 10% de farinha do mesocarpo do fruto do Mari que variou, respectivamente, de 3,7 à 8,6%. Com relação às análises de acidez, umidade e cinzas todos os teores estão dentro dos padrões constantes na legislação brasileira. As análises microbiológicas indicaram não haver a presença de Salmonella sp e Estafilococos coagulase positiva, o crescimento de Coliformes a 35ºC encontraram-se dentro dos padrões estabelecidos pela legislação vigente. Os biscoitos tipo cookie enriquecidos se caracterizaram como alimento funcional por serem ricos em minerais e proteínas devido aos ingredientes da formulação.

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

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Bonnet Amandine

2012-09-01

Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

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Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the

Epithelial cells detect functional type III secretion system of enteropathogenic Escherichia coli through a novel NF-κB signaling pathway.

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Yael Litvak

2017-07-01

Full Text Available Enteropathogenic Escherichia coli (EPEC, a common cause of infant diarrhea, is associated with high risk of mortality in developing countries. The primary niche of infecting EPEC is the apical surface of intestinal epithelial cells. EPEC employs a type three secretion system (TTSS to inject the host cells with dozens of effector proteins, which facilitate attachment to these cells and successful colonization. Here we show that EPEC elicit strong NF-κB activation in infected host cells. Furthermore, the data indicate that active, pore-forming TTSS per se is necessary and sufficient for this NF-κB activation, regardless of any specific effector or protein translocation. Importantly, upon infection with wild type EPEC this NF-κB activation is antagonized by anti-NF-κB effectors, including NleB, NleC and NleE. Accordingly, this NF-κB activation is evident only in cells infected with EPEC mutants deleted of nleB, nleC, and nleE. The TTSS-dependent NF-κB activation involves a unique pathway, which is independent of TLRs and Nod1/2 and converges with other pathways at the level of TAK1 activation. Taken together, our results imply that epithelial cells have the capacity to sense the EPEC TTSS and activate NF-κB in response. Notably, EPEC antagonizes this capacity by delivering anti-NF-κB effectors into the infected cells.

Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF-kB.

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Ricciardolo, F L M; Petecchia, L; Sorbello, V; Di Stefano, A; Usai, C; Massaglia, G M; Gnemmi, I; Mognetti, B; Hiemstra, P S; Sterk, P J; Sabatini, F

2016-03-01

Bradykinin (BK) mediates acute allergic asthma and airway remodelling. Nuclear factor-kappa B (NF-kB) is potentially involved in BK B2 receptor (B2R) regulation. In this observational cross-sectional study, B2R and NF-kB expression was evaluated in bronchial biopsies from mild asthmatics (after diluent/allergen challenge) and healthy controls, examining the role of NF-kB in B2R expression in primary human fibroblasts from normal and asthmatic subjects (HNBFb and HABFb). B2R and NF-kB (total and nuclear) expression was analysed by immunohistochemistry in biopsies from 10 mild intermittent asthmatics (48 h after diluent/allergen challenge) and 10 controls undergoing bronchoscopy. B2R co-localization in 5B5(+) and αSMA(+) mesenchymal cells was studied by immunofluorescence/confocal microscopy, and B2R expression in HABFb/HNBFb incubated with interleukin (IL)-4/IL-13 with/without BK, and after NF-kB inhibitor, by Western blotting. Bronchial mucosa B2R and nuclear NF-kB expression was higher in asthmatics after diluent (B2R only) and allergen challenge than in controls (P kB (total and nuclear) increased after allergen compared with after diluent (P kB inhibitor (P kB expression. NF-kB inhibitor blocked IL-4/IL-13-induced increase in B2R expression in cultured fibroblasts, suggesting a role as potential anti-asthma drug. © 2015 John Wiley & Sons Ltd.

Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-κB signaling pathway.

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Li, Gang; Wang, Ziming; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen

2017-10-01

The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment. The expression of NF-κB signaling related proteins in ACHN cells and xenografts was detected by western blot analysis. The results showed that curcumin significantly increased radiosensitivity of ACHN cells by inhibiting the cell proliferation and DNA damage repair, causing cell cycle arrest at G2/M phase, inducing apoptosis in vitro, and suppressing the growth of xenografts in vivo. In addition, curcumin enhanced radiosensitivity was through markedly inhibiting IR-induced NF-κB signaling by modulating the related protein expressions including NF-κBP65, I-κB, VEGF, COX2, and Bcl-2 in ACHN cells, which was further strengthened by NF-κB inhibitor PDTC treatment. Thus, curcumin may confer radiosensitivity on RCC via inhibition of NF-κB activation and its downstream regulars, suggesting the potential application of curcumin as an adjuvant in radiotherapy of RCC. Copyright © 2017. Published by Elsevier Masson SAS.

Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

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Gao, Hui; Wang, Jianrong

2016-02-01

Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.

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Yvonne Imielski

Full Text Available Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.

Regrowing the Adult Brain: NF-κB Controls Functional Circuit Formation and Tissue Homeostasis in the Dentate Gyrus

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Imielski, Yvonne; Schwamborn, Jens C.; Lüningschrör, Patrick; Heimann, Peter; Holzberg, Magdalena; Werner, Hendrikje; Leske, Oliver; Püschel, Andreas W.; Memet, Sylvie; Heumann, Rolf; Israel, Alain; Kaltschmidt, Christian; Kaltschmidt, Barbara

2012-01-01

Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders. PMID:22312433

Geranylgeranylacetone ameliorates lung ischemia/reperfusion injury by HSP70 and thioredoxin redox system: NF-kB pathway involved.

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Cao, Weijun; Li, Manhui; Li, Jianxiong; Li, Chengwei; Xu, Xin; Gu, Weiqing

2015-06-01

Geranylgeranylacetone (GGA) has been clinically used as an anti-ulcer drug. In the present study, we explored the protective effects of GGA on lung ischemia/reperfusion injury (IRI) and the underlying mechanism. The results demonstrated that GGA ameliorated the lung biochemical and histological alterations induced by IRI, which was reversed by HSP70 inhibition. To further explore the mechanism of GGA action, we focused on NF-kB and thioredoxin (Trx) redox system. It was shown that GGA induced the HSP70 and Trx-1 expression, NF-kB nuclear translocation and activated thioredoxin reductase (TrxR). The Trx-1 expression and TrxR activity was suppressed by HSP70 and NF-kB inhibition, while the nuclear NF-kB p65 expression was suppressed by HSP70 inhibitor. These results indicated that GGA may protect rat lung against IRI by HSP70 and Trx redox system, in which NF-kB pathway may be involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

Eggshell membrane hydrolyzates activate NF-κB in vitro: possible implications for in vivo efficacy

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Ruff KJ

2015-02-01

Full Text Available Kevin J Ruff,1 Paul L Durham,2 Austin O’Reilly,2 F Daniel Long1 1ESM Technologies, LLC, Carthage, MO, USA; 2Center for Biomedical and Life Sciences, Missouri State University, Springfield, MO, USA Purpose: Eggshell membrane (ESM has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB is a signaling protein found in the cytoplasm of nearly all human and animal cell types and is a primary regulator of immune function. The studies reported herein were designed to investigate the possible role that NF-κB activity might play in the reported biological activities of ESM. Methods: Three ESM hydrolyzates produced via fermentation, enzymatic, or chemical hydrolysis were evaluated in vitro in either human peripheral blood mononuclear cell or THP-1 (human leukemic monocyte cell cultures for NF-κB activity following 4-hour exposure. The hydrolyzates were compared with untreated control cells or cells incubated with lipopolysaccharide or ascorbic acid. The source of ESM activity was also evaluated. Results: NF-κB levels were increased above levels found in untreated cells at all three dilutions (1:100, 1:1,000, and 1:10,000 for the fermentation hydrolyzate of ESM (ESM-FH (P=0.021, P=0.020, P=0.009, respectively in peripheral blood mononuclear cells. The enzymatic hydrolyzate of ESM (ESM-EH also produced statistically significant levels of activated NF-κB at the 1:100 and 1:1,000 dilutions (P=0.004, P=0.006, respectively but fell just shy of significance at the 1:10,000 dilution (P=0.073. Similarly, ESM-FH (P=0.021, P=0.002 and ESM-EH (P=0.007, P=0.007 activated NF-κB in THP-1 cells at 1:1,000 and 1:10,000 dilutions, respectively. The chemical hydrolyzate of ESM (ESM-CH showed statistically

NF3: UV Absorption Spectrum Temperature Dependence and the Atmospheric and Climate Forcing Implications

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Papadimitriou, Vassileios C.; McGillen, Max R.; Fleming, Eric L.; Jackman, Charles H.; Burkholder, James B.

2013-01-01

Nitrogen trifluoride (NF3) is an atmospherically persistent greenhouse gas that is primarily removed by UV photolysis and reaction with O((sup 1)D) atoms. In this work, the NF3 gas-phase UV absorption spectrum, sigma(delta,T), was measured at 16 wavelengths between 184.95 and 250 nm at temperatures between 212 and 296 K. A significant spectrum temperature dependence was observed in the wavelength region most relevant to atmospheric photolysis (200-220 nm) with a decrease in sigma(210 nm,T) of approximately 45 percent between 296 and 212 K. Atmospheric photolysis rates and global annually averaged lifetimes of NF3 were calculated using the Goddard Space Flight Center 2-D model and the sigma(delta,T) parameterization developed in this work. Including the UV absorption spectrum temperature dependence increased the stratospheric photolysis lifetime from 610 to 762 years and the total global lifetime from 484 to 585 years; the NF3 global warming potentials on the 20-, 100-, and 500-year time horizons increased less than 0.3, 1.1, and 6.5 percent to 13,300, 17,700, and 19,700, respectively.

Aquaporins 1, 3 and 8 expression in irritable bowel syndrome rats' colon via NF-κB pathway.

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Chao, Guanqun; Zhang, Shuo

2017-07-18

Our research was to detect the expression of aquaporins. NF-κB in Irritable bowel syndrome (IBS) rat models' colon so as to find novel pathogenesisof IBS. The expression of AQP1, AQP3, and AQP8 of IBS model group was down-regulated while NF-κB p65 was up-regulated comparing with control group (p intestine permeability alteration might be the mechanism of IBS by down-regulating AQP1, AQP3 and AQP8 via NF-κB pathway.

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

Science.gov (United States)

Shanmugam, Rajasubramaniam; Gade, Padmaja; Wilson-Weekes, Annique; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A; Baghdadi, Tareq Al; Sargent, Katie J; Cripe, Larry D; Kalvakolanu, Dhananjaya V; Boswell, H Scott

2012-01-15

Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c-Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NF-κB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF-κB. Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. ©2011 AACR.

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

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Jiang, Lili; Wu, Jueheng; Yang, Yi; Liu, Liping; Song, Libing; Li, Jun; Li, Mengfeng

2012-01-01

The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic

Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

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Jiang Lili

2012-09-01

Full Text Available Abstract Background The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1 has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF

Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With Osteomalacia-like Bone Phenotype.

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Kamiya, Nobuhiro; Yamaguchi, Ryosuke; Aruwajoye, Olumide; Kim, Audrey J; Kuroyanagi, Gen; Phipps, Matthew; Adapala, Naga Suresh; Feng, Jian Q; Kim, Harry Kw

2017-08-01

Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH) 2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization

BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

International Nuclear Information System (INIS)

Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei; Yuan, Chuan-Tao; Wang, Ai-Liang

2015-01-01

Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver.

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Li, Xinwei; Huang, Weikun; Gu, Jingmin; Du, Xiliang; Lei, Lin; Yuan, Xue; Sun, Guoquan; Wang, Zhe; Li, Xiaobing; Liu, Guowen

2015-10-01

Dairy cows with fatty liver are characterized by hepatic lipid accumulation and a severe inflammatory response. Sterol receptor element binding protein-1c (SREBP-1c) and nuclear factor κB (NF-κB) are components of the main pathways for controlling triglyceride (TG) accumulation and inflammatory levels, respectively. A previous study demonstrated that hepatic inflammatory levels are positively correlated with hepatic TG content. We therefore speculated that SREBP-1c might play an important role in the overactivation of the hepatic NF-κB inflammatory pathway in cows with fatty liver. Compared with healthy cows, cows with fatty liver exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6 and IL-1β. Hepatic SREBP-1c-mediated lipid synthesis and the NF-κB inflammatory pathway were both overinduced in cows with fatty liver. In vitro, treatment with non-esterified fatty acids (NEFA) further increased SREBP-1c expression and NF-κB pathway activation, which then promoted TG and inflammatory cytokine synthesis. SREBP-1c overexpression overactivated the NF-κB inflammatory pathway in hepatocytes by increasing ROS content and not through TLR4. Furthermore, SREBP-1c silencing decreased ROS content and further attenuated the activation of the NEFA-induced NF-κB pathway, thereby decreasing TNF-α, IL-6 and IL-1β synthesis. SREBP-1c-overexpressing mice exhibited hepatic steatosis and an overinduced hepatic NF-κB pathway. Taken together, these results indicate that SREBP-1c enhances the NEFA-induced overactivation of the NF-κB inflammatory pathway by increasing ROS in cow hepatocytes, thereby further increasing hepatic inflammatory injury in cows with fatty liver. Copyright © 2015. Published by Elsevier Inc.

Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice.

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Alexander, George; Carlsen, Harald; Blomhoff, Rune

2006-04-01

To determine the dynamics of Nuclear Factor-kappaB (NF-kappaB) in murine corneal pathology and the role of NF-kappaB in maintaining corneal clarity after ultraviolet B radiation insult, transgenic mice containing NF-kappaB-luciferase reporter were exposed to LPS (bacterial lipopolysaccharide), TNF-alpha (Tumor Necrosis Factor-alpha) or 4 kJ m(-2) UV-B radiation. NF-kappaB decoy oligonucleotides were also administered in some of the UV-B experiments. Following various exposure times, the mice were sacrificed and whole eyes or corneal tissues were obtained. Whole eyes were examined for scattering using a point-source optical imaging technique. Tissue homogenates were examined for luciferase activity using a luminometer. TNF-alpha and LPS-injected NF-kappaB-luciferase transgenic mice demonstrated 3-10-fold increases in cornea NF-kappaB with peak activities at 4 and 6 hr post-injection, respectively. Mice exposed to 4 kJ m(-2) UV-B exhibited a 3-fold increase in NF-kappaB activity 4 hr post-exposure. The administration of NF-kappaB-decoy oligonucleotides to mice had the effect of reducing UV-B-induced NF-kappaB activity in the cornea and significantly increasing the amount of light scattering in UV-B exposed corneas 7 days post-UV-B exposure when compared to sham injected mice. These results indicate that NF-kappaB is activated in cornea in pathologies that involves increased plasma levels of LPS and TNF-alpha, as well as direct UV-B exposure, and suggest that NF-kappaB activation play an essential part in the corneal healing process.

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

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Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

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Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

GeNF - experimental report 2003

International Nuclear Information System (INIS)

Schreyer, A.; Vollbrandt, J.; Willumeit, R.

2004-01-01

At the Geesthacht Neutron Facility GeNF about 210 experiments were performed in 2003 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guest and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2003. The contributions may contain one or also several combined experiments. During 2003 the GKSS research reactor FRG-1 achieved an operation time of 252 days at the full 5 MW reactor power providing a neutron flux of ca. 1,4 x 10 14 thermal neutrons / cm 2 s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of metal alloys, the analysis of stresses in welds and technical structures at ARES, FSS, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR and ROeDI. The reflectomer TOREMA was thoroughly upgraded to the instrument NeRo and now offers new measurement possibilities. In the appendices the progress of the project REFSANS at FRM-II is reported as well as the experimental activities of the newly installed GKSS outstation HARWI-II at DESY. (orig.)

GeNF - experimental report 2003

Energy Technology Data Exchange (ETDEWEB)

Schreyer, A; Vollbrandt, J; Willumeit, R [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. for Materials Research

2004-07-01

At the Geesthacht Neutron Facility GeNF about 210 experiments were performed in 2003 by GKSS and by or for external users, partners or contractors. In most cases the measurements were performed and analysed in cooperation by the guest and by the GKSS staff or by the permanent external user group staff. The activities, which are based on a proposal procedure and on the in house R and D program, are reported in 76 contributions in the present annual experimental report for the year 2003. The contributions may contain one or also several combined experiments. During 2003 the GKSS research reactor FRG-1 achieved an operation time of 252 days at the full 5 MW reactor power providing a neutron flux of ca. 1,4 x 10{sup 14} thermal neutrons / cm{sup 2} s. The cold neutron source was available during the complete operation time. The focus of the in house R and D work at GeNF instruments was the characterisation of metal alloys, the analysis of stresses in welds and technical structures at ARES, FSS, DCD and SANS-2, the structural investigation of hydrogen containing substances such as polymers, colloids and biological macromolecules at SANS-1 as well as the characterisation of magnetic thin films at PNR and ROeDI. The reflectomer TOREMA was thoroughly upgraded to the instrument NeRo and now offers new measurement possibilities. In the appendices the progress of the project REFSANS at FRM-II is reported as well as the experimental activities of the newly installed GKSS outstation HARWI-II at DESY. (orig.)

Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-κB Activity in Intestine

OpenAIRE

Wu, Shaoping; Liao, Anne P.; Xia, Yinglin; Li, Yan Chun; Li, Jian-Dong; Sartor, R. Balfour; Sun, Jun

2010-01-01

Vitamin D receptor (VDR) plays an essential role in gastrointestinal inflammation. Most investigations have focused on the immune response; however, how bacteria regulate VDR and how VDR modulates the nuclear factor (NF)-κB pathway in intestinal epithelial cells remain unexplored. This study investigated the effects of VDR ablation on NF-κB activation in intestinal epithelia and the role of enteric bacteria on VDR expression. We found that VDR−/− mice exhibited a pro-inflammatory bias. After ...

Long-term performance and fouling analysis of full-scale direct nanofiltration (NF) installations treating anoxic groundwater

NARCIS (Netherlands)

Beyer, F.; Rietman, B.M.; Zwijnenburg, A.; Brink, van den P.; Vrouwenvelder, J.S.; Jarzembowska, M.; Laurinonyte, J.; Stams, A.J.M.; Plugge, C.M.

2014-01-01

Long-term performance and fouling behavior of four full-scale nanofiltration (NF) plants, treating anoxic groundwater at 80% recovery for drinking water production, were characterized and compared with oxic NF and reverse osmosis systems. Plant operating times varied between 6 and 10 years and

Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts.

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Aaron C-H Chen

Full Text Available Despite over forty years of investigation on low-level light therapy (LLLT, the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear.In this study, we isolated murine embryonic fibroblasts (MEF from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm(2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration.We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.

1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naive B cells

International Nuclear Information System (INIS)

Geldmeyer-Hilt, Kerstin; Heine, Guido; Hartmann, Bjoern; Baumgrass, Ria; Radbruch, Andreas; Worm, Margitta

2011-01-01

Highlights: → In naive B cells, VDR activation by calcitriol results in reduced NF-κB p105 and p50 protein expression. → Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-κB p65. → Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. → Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1α,25-dihydroxyvitamin D 3 (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naive B cells. Naive B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naive B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.

Role of monoubiquitylation on the control of IκBα degradation and NF-κB activity.

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Elisa Da Silva-Ferrada

Full Text Available The NF-κB pathway is regulated by multiple post-translational modifications including phosphorylation, ubiquitylation and SUMOylation. Many of these modifications act on the natural inhibitor IκBα modulating its capacity to control signal-mediated NF-κB activity. While the canonical pathway involving the phosphorylation and polyubiquitylation of IκBα has been well characterized, the role of these post-translational modifications in the control of basal NF-κB activity has not been deeply explored. Using the recently developed Tandem-repeated Ubiquitin Binding Entities (also known as ubiquitin traps to capture ubiquitylated proteins, we identified monoubiquitylated forms of IκBα from multiple rat organs and cell types. The identification of these forms was demonstrated through different procedures such as immunoprecipitations with specific ubiquitin antibodies or His6-Ubiquitin pull downs. Monoubiquitylated forms of IκBα are resistant to TNFα-mediated degradation and can be captured using TUBEs, even after proteasome inhibitors treatment. As it occurs for monoSUMOylation, monoubiquitylation is not dependent of the phosphorylation of IκBα on the serines 32/36 and is not optimally degraded after TNFα stimulation. A ubiquitin-IκBα fusion exhibits phosphorylation defects and resistance to TNFα mediated degradation similar to the ones observed for endogenous monoubiquitylated IκBα. The N-terminal attachment of a single ubiquitin moiety on the IκBα fusion results in a deficient binding to the IKKβ kinase and recruitment of the SCF ligase component βTrCP, promoting a negative impact on the NF-κB activity. Altogether, our results suggest the existence of a reservoir of monoubiquitylated IκBα resistant to TNFα-induced proteolysis, which is able to interact and repress DNA binding and NF-κB transcriptional activity. Such pool of IκBα may play an important role in the control of basal and signal-mediated NF-κB activity.

Removing Fe, Zn and Mn from steel making plant wastewater using RO and NF membranes

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Seyed Ahmad Mirbagheri

2016-12-01

Full Text Available Background and purpose: Excessive amount of heavy metals in industrial wastewater is a seriously crucial issue and requires efficient methods to be introduced and dealt with. Meanwhile, steel making plants as productive units in every country release large amounts of fluid into surface and underground sources. Typically, this wastewater contains heavy metals in minor amounts, while this amount could cause severe damages to the living organisms. Materials and methods: In this study, removing iron, manganese, zinc and total dissolved solid in a typical wastewater resulted from steel making plant was considered using reverse osmosis (RO and nanofiltration (NF membranes. At first, different pH values and operating pressures were applied to the wastewater. Then, these parameters were evaluated for a wastewater only containing iron to compare the interaction of other elements in iron removal. Results: The results indicated that RO and NF membranes could successfully treat industrial wastewater containing several heavy metals with high concentrations of Fe, Zn and Mn, especially at optimum pH and pressure. Moreover, the interaction of other heavy metals and components in the influent decreased the efficiency of RO but improved the NF efficiency to remove iron. To have a better image, a formula was proposed for each method to represent the influence of the parameters on removal rates. Finally, cost estimation for both procedures showed that RO was not economically-technically efficient in comparison with NF. Conclusion: NF showed an acceptable performance with high water flow which made it more suitable for industries. At the end, the relative cost analysis showed that even if the initial price of NF is high, the energy consumption and total cost of RO will be higher.

Lactic acid production by irradiated Bacillus NF17 and poly-L-lactate biopolymer formation

International Nuclear Information System (INIS)

Tongpim, Saowanit; Poonsawat, Choosak; Khansawai, Paveena; Piadaeng, Nattaya

2006-09-01

This study was conducted to manipulate the thermo tolerant, lactic acid-producing bacteria, Bacillus coagulans strain NF 1 7, in the production of L-lactic acid and a bio polymer: poly-L-lactate. The bacterial isolate NF 1 7 kept in the culture collection of Khon Kaen University and could tolerate high temperature and produce lactic acid, was employed in this research work. Cell suspension of isolate NF 1 7 was exposed to gamma irradiation at various doses (1-5 KGy). The irradiated survivors were screened on the basis of forming larger colonies and clear zones than the parent strain NF 1 7 when grown on Glucose-Yeast extract-Peptone (GYP) containing CaCO 3 . We obtained 55 effective isolates which the isolate L5I2-14(5), designated as K 1 4, was chosen together with the parent strain NF 1 7 for fermentation experiments. Each bacterial strain was inoculated into GYP broth and incubated statically at 50 o C with daily pH neutralization. After 5 days of incubation, the isolate K 1 4 and NF 1 7 produced 9.71 g/l and 7.42 g/l of L-lactic acid, respectively with a small amount of D-lactic acid. Lactic acid production from sugar cane molasses by batch fermentation of Bacillus Sp. K 1 4 was carried out in a 7 l jar fermentor containing 5 l of fermentation medium. It was found that 20% molasses with the agitation speed of 100 rpm gave the highest yield of lactic acid. Poly-L-lactic acid was chemically polymerized by bulk polymerization process at 140 o C under 40 mmHg conditions. We could obtain the off-white polymer in a small amount of powder form. Improvement the yield of poly-L-lactic acid would be achieved by using polyisoprene-g-polyvinyl monomer to separate lactic acid from the fermenting liquid prior to polymerization processes

NF-κB inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats

International Nuclear Information System (INIS)

Zhong Caiyun; Zhou Yamei; Pinkerton, Kent E.

2008-01-01

Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-κB) in this process. Exposure of rats to 80 mg/m 3 tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-κB activity, noted by suppression of inhibitor of κB (IκB) kinase (IKK), accumulation of IκBα, decrease of NF-κB DNA binding activity, and downregulation of NF-κB-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-κB pathway in tobacco smoke-induced apoptosis

Induction of oncogene addiction shift to NF-κB by camptothecin in solid tumor cells

International Nuclear Information System (INIS)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

2009-01-01

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-κB activity driven by IκB kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-κB during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-κB inhibitors.