Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of ...these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.
To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility.
Experimental.
University ...laboratory.
Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH.
Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol.
Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles.
Plasma insulin and T levels decreased and Homeostatic Index of Insulin Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-α levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group.
Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.
Instability and high permeability are two of the problems facing tunnelling excavations in soils with high fines content. Among the different techniques used to improve these soils, the injection of ...cement grouts stands out. In this work, a grouting treatment is designed to ensure the stability of the ground during the construction of two tunnels linking two municipalities in the north of Spain in Biscay, and to reduce the inflow of water from the aquifer located in the vicinity of these tunnels. First of all, the rock mass is analysed and the material to be injected is selected on the basis of the authors’ experience as well as setting time and compressive strength. Subsequently, with a test device designed by the DinRock research group of the University of Oviedo, two types of laboratory tests are carried out in order to analyse the effect of fines migration and washing on the water flows and the effect of re-injections of grouts with different densities on the permeability value. The results show that, in sandy materials, obtaining high degrees of waterproofing together with large stable zones can only be achieved by a combination of treatments and stages with different materials and densities. In addition, maximum values for both injection pressure and flow rate must be established depending on the type of grout and the permeability of the soil. Once the problem has been analysed, the injection treatment is designed and executed. The treatment consists of one pre-injection in four stages with 30 boreholes drilled in the top heading, 19–20 boreholes drilled in the bench, and one post-injection with boreholes drilled around the perimeter of the tunnel in those areas where the pre-injection does not achieve the desired degree of waterproofing.
In the last decades, rigorous research has been carried out with the end of understanding the gas dynamic phenomenon and although different preventive techniques have been employed, even today there ...are numerous accidents even with the loss of life. This work analyses an alternative and innovative method of fracturing and degassing coal, by generating CO2 with a pyrotechnic device called PYROC (Pyrotechnic Break Cartridges). Medium-scale tests of generation of CO2 into coal samples are carried out and their effect is analysed comparing the initial and final permeabilities of the coal samples once the generation of CO2 has finished. These permeabilities are calculated by injecting methane. Besides, the influence of different parameters as the length of the boreholes, the pressure of the gas or the initial permeability of the coal have been analysed with a numerical simulation of one face of one of the sublevels of a mine. The results show that the method increases the safety in mining operations because it fractures and degasses the coal, increases the permeability of the coal in the borehole of injection from 9.5 mD to 31 mD, decreases the methane gas pressure below pre-detonation levels for 1 min, achieves decompressed lengths between 8 and 10 m ahead of the face with pressures of injection of 50 MPa, relaxes the total length of the borehole for initial coal permeability values equal to or greater than 0.002 mD, and allows to work with low permeable coals with high induced stresses and high methane concentrations.
Menopause leads to a decrease in estrogen production that increases central insulin resistance, contributing to the development of neurodegenerative diseases. We have evaluated the influence of aging ...and estradiol or genistein treatments on some key stages of the insulin signaling pathway in the cerebral cortex. Young and aged female Wistar rats were ovariectomized and treated acutely with 17β-estradiol (1.4μg/kg body weight), two doses of genistein (10 or 40mg/kg body weight), or vehicle. The cortical expression of several key insulin signaling pathway components was analyzed by western blotting. Our results showed an age-related deterioration in the interactions between the regulatory subunit of phosphatidylinositol 3-kinase (p85α) and the activated form of insulin receptor substrate 1 (p-IRS1tyr612), as well as between p85α and the 46kDa isoform of the estrogen receptor α (ERα46). Moreover, aging also decreased the translocation of glucose transporter-4 (GLUT4) to the plasma membrane. 17β-Estradiol but not genistein reduced the negative impact of aging on central insulin sensitivity by favoring this GLUT4 translocation, and therefore could be neuroprotective against the associated neurodegenerative diseases. However, protein kinase B (Akt) activation by genistein suggests that other possible mechanisms are involved in the neuroprotective effects of this phytoestrogen during the aging process.
•An age-related decline was found in p-IRS1tyr612–p85α and ERα46–p85α interactions.•Aging impaired GLUT4 translocation to the plasma membrane.•ERα67 and ERα46 showed different interaction degree with IRS1 and p85α.•Both estradiol and genistein stimulate AKT phosphorylation in aged rats.•Only estradiol enhanced GLUT4 translocation to plasma membrane in aged rats.
Fractured rock masses below the water table are a problem in underground excavations because of their low strength and high permeability. Nowadays, these negative connotations can be reduced with ...techniques such as injection of cement, microcement, or resins grouts. These materials increase the rock mass cohesion while reducing the flow of water through the discontinuities. This paper describes the work carried out to design a waterproofing screen for a three-storey underground basement located in a building near the Bilbao estuary (Northern Spain) and with problems of water seepage from the river. First, a survey of the rock mass is carried out. This survey shows the presence of highly fractured zones and the variability of the permeability as functions of the fractures. Subsequently, the effect on permeability caused by the injection of cement grouts and microcement is studied by means of two pilot injection boreholes and eight control boreholes. Finally, a behavioural model is proposed to explain the heterogeneity observed in the radius of influence of the injection. As a result, a waterproofing screen with three types of treatment is designed: An ordinary treatment with cement grouts, an intensive treatment with microcement grouts, and an isolation treatment with cement-bentonite grouts.
The need for large and fast excavations, together with noise and vibration limitations, means that mechanical removal is increasingly used rather than blasting. In mechanical removal, the cutting ...tools hit the rock and penetrate it, and then move in the direction of cutting, dragging and detaching a portion of rock called chip. Most research on mechanical removal approaches it as a static process without taking into account the speed at which the cutting element impacts the rock. This work presents the design of a pendulum equipment capable of simulating the impact of a cutting element, specifically a pick, against a rock, reproducing the removal in a similar way to how it is carried out in real excavations. Cutting tests are carried out with concrete samples with a cement/sand ratio of 1:1 and 3:1, the volume of material that is removed is calculated using a 3D scanner and images of the tests are collected with a high-speed video camera to facilitate the interpretation of the results. The results confirm the direct relationship between impact energy, chip size and cutting depth, prove the formation of an affected zone that allows to reduce the cutting energy, and empirically obtain the optimum cutting energy with which the maximum performance in mechanical removal would be achieved.
Uniaxial compressive strength is an essential mechanical parameter to adequately characterize any given material. Numerous standards have been developed to guarantee reliable testing execution, as ...well as the repeatability of results. In this sense, not only the geometric dimensions and tolerances of both the platen and the specimen have been prescribed, but also the testing parameters, such as the load application speed. However, all these recommendations are based on the assumption that the stresses are uniformly distributed across the contact interface between the platen and the specimen. Nevertheless, this is major elastic simplification that allows for obtaining a handy and useful formula to determine the compressive strength, but this strongly deviates the theoretical foundations from the actual experimental reality. Experimental and numerical research to determine the influence of relative stiffness between the specimen and the platen on the stress distribution generated during the execution of the uniaxial compressive test is performed. The results prove that the stresses are not uniformly distributed across the contact when the platen material is significantly stiffer or softer (less stiff) than that of the tested specimen, and additionally, an undesired triaxial stress field is induced inside the specimen. For these reasons, the use of platens with a similar stiffness to that of the specimen is strongly recommended, as it allows for the uniform distribution of the compressive contact stresses and minimizes the influence of the triaxial stress field.
The relationship between estrogen and some types of breast cancer has been clearly established. However, although several studies have demonstrated the relationship between estrogen and glucose ...uptake via phosphatidylinositol 3-kinase (PI3K)/Akt in other tissues, not too much is known about the possible cross talk between them for development and maintenance of breast cancer. This study was designed to test the rapid effects of 17β-estradiol (E2) or its membrane-impermeable form conjugated with BSA (E2BSA) on glucose uptake in a positive estrogen receptor (ER) breast cancer cell line, through the possible relationship between key components of the PI3K/Akt signaling pathway and acute steroid treatment. MCF-7 human breast cancer cells were cultured in standard conditions. Then 10 nM E2 or E2BSA conjugated were administered before obtaining the cell lysates. To study the glucose uptake, the glucose fluorescent analog 2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxy-d-glucose was used. We report an ER-dependent activation of some of the key steps of the PI3K/Akt signaling pathway cascade that leads cells to improve some mechanisms that finally increase glucose uptake capacity. Our data suggest that both E2 and E2BSA enhance the entrance of the fluorescent glucose analog 2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxy-d-glucose, and also activates PI3K/Akt signaling pathway, leading to translocation of glucose transporter 4 to the plasma membrane in an ERα-dependent manner. E2 enhances ER-dependent rapid signaling triggered, partially in the plasma membrane, allowing ERα-positive MCF-7 breast cancer cells to increase glucose uptake, which could be essential to meet the energy demands of the high rate of proliferation.
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