scholarly journals A potential protective mechanism of soya isoflavones against 7,12-dimethylbenz[a]anthracene tumour initiation

2003 ◽  
Vol 90 (2) ◽  
pp. 457-465 ◽  
Author(s):  
Ho Yee Chan ◽  
Lai K. Leung

Epidemiological studies indicate that Asian women have a lower breast cancer incidence compared with their counterparts in the West, and the difference has been related to soya consumption. Animal studies have suggested that soya may prevent dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in the breast. In the present study a cell culture model was developed to address the effect of soya isoflavones on the DMBA-induced DNA damage. DMBA is metabolized into a DNA-attacking moiety by two phase I cytochrome P450 (CYP) enzymes CYP1A1 and CYP1B1. DNA mutation caused by this genotoxic agent is a crucial step in cancer initiation. Substances that interfere with the CYP1 enzyme activities can affect the initiation. In the present study, genistein was found to be an effective inhibitor of recombinant human CYP1A1 and CYP1B1 with Ki of 15·35 and 0·68 μmol/l. The other soya isoflavone daidzein, on the other hand, did not demonstrate any significant inhibition of the enzyme activities. At the transcriptional level, DMBA induced the CYP1 enzyme expressions by stimulating the xenobiotic response element (XRE)-dependent transactivation pathway. When genistein (25 μmol/l) was co-administered with DMBA, the XRE-Luc activity the CYP1 mRNA abundances were significantly suppressed. The present study illustrated that the soya isoflavone genistein, but not daidzein, protected against DMBA genotoxicity.

2015 ◽  
Vol 67 (3) ◽  
pp. 861-867
Author(s):  
Syed Nurulain ◽  
Mohamed Shafiullah ◽  
Charu Sharma ◽  
Mahmoud Ali ◽  
Shreesh Ojha

A convincing number of epidemiological studies have reported on the exposure to and consequences of organophosphorus compounds (OPCs) in pregnant women. However, there is still a knowledge gap and paucity of systematic literature from animal studies. This study was undertaken with the hypothesis that short-duration sublethal exposure to OPCs can produce maternal and fetal lethal effects as chronic exposure. This study examineses the teratogenicity and embryotoxicity of paraoxon (POX) in mice at a dose that is non-lethal to non-pregnant mothers. Pregnant mice were injected intraperitoneally (i.p.) with paraoxon (50 nmol/mouse) on the 4th and 5th days of gestation, and the effect of the treatment was assessed on day 18 of gestation. This dose was fatal to pregnant mice in 21% of instances as compared to non-pregnant animals in which 0% mortality was detected, even after daily injection of a similar dose for five days. Significant inhibition of red blood cell acetylcholinesterase (RBC-AChE) was observed in pregnant mice as compared to non-pregnant ones; however, no apparent neuronal effect was detected. Of note were fetal weight decrement, pregnancy termination, intrauterine growth retardation and maternal death. We concluded that exposure to even a non-toxic dose might be critical for pregnant mothers, the pregnancy as well as fetuses. In addition, even exposure of short duration can be detrimental and capable of producing profound and fatal effects.


2021 ◽  
Vol 10 (2) ◽  
pp. 366
Author(s):  
Anke Hoffmann ◽  
Dietmar Spengler

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans.


Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.


2001 ◽  
Vol 15 (18) ◽  
pp. 2491-2497 ◽  
Author(s):  
J. L. ZHU ◽  
L. C. CHEN ◽  
R. C. YU ◽  
F. Y. LI ◽  
J. LIU ◽  
...  

In situ high pressure energy dispersive X-ray diffraction measurements on layered perovskite-like manganate Ca 3 Mn 2 O 7 under pressures up to 35 GPa have been performed by using diamond anvil cell with synchrotron radiation. The results show that the structure of layered perovskite-like manganate Ca 3 Mn 2 O 7 is unstable under pressure due to the easy compression of NaCl-type blocks. The structure of Ca 3 Mn 2 O 7 underwent two phase transitions under pressures in the range of 0~35 GPa. One was at about 1.3 GPa with the crystal structure changing from tetragonal to orthorhombic. The other was at about 9.5 GPa with the crystal structure changing from orthorhombic back to another tetragonal.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marlene Cervantes González

Abstract Persistent Organic Pollutants (POPs) are exogenous, artificially made chemicals that can disrupt the biological system of individuals and animals. POPs encompass a variety of chemicals including, dioxins, organochlorines (OCs), polychlorinated biphenyl (PCBs), and perfluoroalkyl substances (PFASs) that contain a long half-life and highly resistant to biodegradation. These environmental pollutants accumulate over time in adipose tissues of living organisms and alter various insulin function-related genes. Childhood Metabolic Syndrome (MetS) consists of multiple cardiovascular risk factors, insulin function being one of them. Over the years, the incidence of the syndrome has increased dramatically. It is imperative to explore the role of persistent organic pollutants in the development of Childhood Metabolic Syndrome. Some epidemiological studies have reported an association between prenatal exposure to POPs and offspring MetS development throughout childhood. These findings have been replicated in animal studies in which these pollutants exercise negative health outcomes such as obesity and increased waist circumference. This review discusses the role of prenatal exposure to POPs among offspring who develop MetS in childhood, the latest research on the MetS concept, epidemiological and experimental findings on MetS, and the POPs modes of action. This literature review identified consistent research results on this topic. Even though the studies in this review had many strengths, one major weakness was the usage of different combinations of MetS criteria to measure the outcomes. These findings elucidate the urgent need to solidify the pediatric MetS definition. An accurate definition will permit scientists to measure the MetS as a health outcome properly and allow clinicians to diagnose pediatric MetS and provide individualized treatment appropriately.


2010 ◽  
Vol 23 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Paul Guilloteau ◽  
Romuald Zabielski ◽  
Harald M. Hammon ◽  
Cornelia C. Metges

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.


1984 ◽  
Vol 24 (06) ◽  
pp. 606-616 ◽  
Author(s):  
Charles P. Thomas ◽  
Paul D. Fleming ◽  
William K. Winter

Abstract A mathematical model describing one-dimensional (1D), isothermal flow of a ternary, two-phase surfactant system in isotropic porous media is presented along with numerical solutions of special cases. These solutions exhibit oil recovery profiles similar to those observed in laboratory tests of oil displacement by surfactant systems in cores. The model includes the effects of surfactant transfer between aqueous and hydrocarbon phases and both reversible and irreversible surfactant adsorption by the porous medium. The effects of capillary pressure and diffusion are ignored, however. The model is based on relative permeability concepts and employs a family of relative permeability curves that incorporate the effects of surfactant concentration on interfacial tension (IFT), the viscosity of the phases, and the volumetric flow rate. A numerical procedure was developed that results in two finite difference equations that are accurate to second order in the timestep size and first order in the spacestep size and allows explicit calculation of phase saturations and surfactant concentrations as a function of space and time variables. Numerical dispersion (truncation error) present in the two equations tends to mimic the neglected present in the two equations tends to mimic the neglected effects of capillary pressure and diffusion. The effective diffusion constants associated with this effect are proportional to the spacestep size. proportional to the spacestep size. Introduction In a previous paper we presented a system of differential equations that can be used to model oil recovery by chemical flooding. The general system allows for an arbitrary number of components as well as an arbitrary number of phases in an isothermal system. For a binary, two-phase system, the equations reduced to those of the Buckley-Leverett theory under the usual assumptions of incompressibility and each phase containing only a single component, as well as in the more general case where both phases have significant concentrations of both components, but the phases are incompressible and the concentration in one phase is a very weak function of the pressure of the other phase at a given temperature. pressure of the other phase at a given temperature. For a ternary, two-phase system a set of three differential equations was obtained. These equations are applicable to chemical flooding with surfactant, polymer, etc. In this paper, we present a numerical solution to these equations paper, we present a numerical solution to these equations for I D flow in the absence of gravity. Our purpose is to develop a model that includes the physical phenomena influencing oil displacement by surfactant systems and bridges the gap between laboratory displacement tests and reservoir simulation. It also should be of value in defining experiments to elucidate the mechanisms involved in oil displacement by surfactant systems and ultimately reduce the number of experiments necessary to optimize a given surfactant system.


1972 ◽  
Vol 129 (3) ◽  
pp. 645-655 ◽  
Author(s):  
J. S. Heller ◽  
C. L. Villemez

A neutral-detergent-solubilized-enzyme preparation derived from Phaseolus aureus hypocotyls contains two types of glycosyltransferase activity. One, mannosyltransferase enzyme activity, utilizes GDP-α-d-mannose as the sugar nucleotide substrate. The other, glucosyltransferase enzyme activity, utilizes GDP-α-d-glucose as the sugar nucleotide substrate. The soluble enzyme preparation catalyses the formation of what appears to be a homopolysaccharide when either sugar nucleotide is the only substrate present. A β-(1→4)-linked mannan is the only polymeric product when only GDP-α-d-mannose is added. A β-(1→4)-linked glucan is the only polymeric product when only GDP-α-d-glucose is added. In the presence of both sugar nucleotides, however, a β-(1→4)-linked glucomannan is formed. There are indications that endogenous sugar donors may be present in the enzyme preparation. There appear to be only two glycosyltransferases in the enzyme preparation, each catalysing the transfer of a different sugar to the same type of acceptor molecule. The glucosyltransferase requires the continual production of mannose-containing acceptor molecules for maintenance of enzyme activity, and is thereby dependent upon the activity of the mannosyltransferase. The mannosyltransferase, on the other hand, does not require the continual production of glucose-containing acceptors for maintenance of enzyme activity, but is severely inhibited by GDP-α-P-glucose. These properties promote the synthesis of β-(1→4)-linked glucomannan rather than β-(1→4)-linked glucan plus β-(1→4)-linked mannan when both sugar nucleotide substrates are present.


2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Shohei Yokoo ◽  
Seiya Inoue ◽  
Nana Suzuki ◽  
Naho Amakawa ◽  
Hidenori Matsui ◽  
...  

Isochorismate synthase (ICS) converts chorismate into isochorismate, a precursor of primary and secondary metabolites including salicylic acid (SA). SA plays important roles in responses to stress conditions in plants. Many studies have suggested that the function of plant ICSs is regulated at the transcriptional level. In Arabidopsis thaliana, the expression of AtICS1 is induced by stress conditions in parallel with SA synthesis, and AtICS1 is required for SA synthesis. In contrast, the expression of NtICS is not induced when SA synthesis is activated in tobacco, and it is unlikely to be involved in SA synthesis. Studies on the biochemical properties of plant ICSs are limited, compared with those on transcriptional regulation. We analyzed the biochemical properties of four plant ICSs: AtICS1, NtICS, NbICS from Nicotiana benthamiana, and OsICS from rice. Multiple sequence alignment analysis revealed that their primary structures were well conserved, and predicted key residues for ICS activity were almost completely conserved. However, AtICS1 showed much higher activity than the other ICSs when expressed in Escherichia coli and N. benthamiana leaves. Moreover, the levels of AtICS1 protein expression in N. benthamiana leaves were higher than the other ICSs. Construction and analysis of chimeras between AtICS1 and OsICS revealed that the putative chloroplast transit peptides (TPs) significantly affected the levels of protein accumulation in N. benthamiana leaves. Chimeric and point-mutation analyses revealed that Thr531, Ser537, and Ile550 of AtICS1 are essential for its high activity. These distinct biochemical properties of plant ICSs may suggest different roles in their respective plant species.


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