Dietary fibre and colon cancer: epidemiologic and experimental evidence.

Epidemiologic studies have identified two dietary factors, a relatively high intake of fat and a relatively low intake of fibre, that are associated with colon cancer in humans. However, a recent study has shown a low risk of large bowel cancer in a rural Finnish population with a high dietary intake of fat, but also a high intake of fibre. Observations in humans and studies in animals have indicated that dietary fibre may protect against colon carcinogenesis by binding bile acids in the intestinal tract, by a direct effect on the colonic mucosa and by an indirect effect on the metabolism of carcinogens. The strength of protection varies with the type of fibre.     

Dietary fiber, lipid metabolism, and atherosclerosis

Despite the physiochemical complexity of dietary fibers (plant cell walls) and their individual components, there is substantial epidemiologic, clinical, and experimental evidence that these dietary components may have a role in modifying certain risk factors in coronary heart disease. Particulate fibers, such as wheat bran, do not appear to significantly alter plasma lipids or lipoprotein distributions in humans, or the atherogenicity of diets in experimental animals. Dietary fibers found in fruits, legumes, and vegetables, in contrast, show more definitive responses. Among the fiber isolates, the gelling and mucilaginous fibers, such as pectins and guar gum, predictably decrease circulating lipids in humans and animals and increase excretion of fecal metabolites of cholesterol, the bile acids. These fibers and fiber components can be shown to influence luminal solubility of lipids and the extent of lymphatic absorption of both cholesterol and triglyceride. In addition, these same fibers are effective in reducing postprandial levels of glucose, insulin, and other hormones. These direct effects on lipid absorption, and secondary effects of glucose and insulin on hepatic and peripheral lipoprotein metabolism, can account for many of the hypolipidemic responses to specific dietary fibers or their components, and may be of long-term consequence in coronary heart disease.     

Biology of gut anaerobic fungi

The obligately anaerobic nature of the gut indigenous fungi distinguishes them from other fungi. They are distributed widely in large herbivores, both in the foregut of ruminant-like animals and in the hindgut of hindgut fermenters. Comparative studies indicate that a capacious organ of fermentative digestion is required for their development. These fungi have been assigned to the Neocallimasticaceae, within the chytridiomycete order Spizellomycetales. The anaerobic fungi of domestic ruminants have been studied most extensively. Plant material entering the rumen is rapidly colonized by zoospores that attach and develop into thalli. The anaerobic rumen fungi have been shown to produce active cellulases and xylanases and specifically colonise and grow on plant vascular tissues. Large populations of anaerobic fungi colonise plant fragment in the rumens of cattle and sheep on high-fibre diets. The fungi actively ferment cellulose which results in formation of a mixture of products including acetate, lactate, ethanol, formate, succinate, CO2 and H2. The properties of the anaerobic fungi together with the extent of their populations on plant fragments in animals on high-fibre diets indicates a significant role for the fungi in fibre digestion.     

Amyloids and prions in plants: Facts and perspectives

Amyloids represent protein fibrils that have highly ordered structure with unique physical and chemical properties. Amyloids have long been considered lethal pathogens that cause dozens of incurable diseases in humans and animals. Recent data show that amyloids may not only possess pathogenic properties but are also implicated in the essential biological processes in a variety of prokaryotes and eukaryotes. Functional amyloids have been identified in archaea, bacteria, fungi, and animals, including humans. Plants are one of the most poorly studied groups of organisms in the field of amyloid biology. Although amyloid properties have not been shown under native conditions for any plant protein, studies demonstrating amyloid properties for a set of plant proteins in vitro or in heterologous systems in vivo have been published in recent years. In this review, we systematize the data on the amyloidogenic proteins of plants and their functions and discuss the perspectives of identifying novel amyloids using bioinformatic and proteomic approaches.     

Humans and Mice Express Similar Olfactory Preferences

In humans, the pleasantness of odors is a major contributor to social relationships and food intake. Smells evoke attraction and repulsion responses, reflecting the hedonic value of the odorant. While olfactory preferences are known to be strongly modulated by experience and learning, it has been recently suggested that, in humans, the pleasantness of odors may be partly explained by the physicochemical properties of the odorant molecules themselves. If odor hedonic value is indeed predetermined by odorant structure, then it could be hypothesized that other species will show similar odor preferences to humans. Combining behavioral and psychophysical approaches, we here show that odorants rated as pleasant by humans were also those which, behaviorally, mice investigated longer and human subjects sniffed longer, thereby revealing for the first time a component of olfactory hedonic perception conserved across species. Consistent with this, we further show that odor pleasantness rating in humans and investigation time in mice were both correlated with the physicochemical properties of the molecules, suggesting that olfactory preferences are indeed partly engraved in the physicochemical structure of the odorant. That odor preferences are shared between mammal species and are guided by physicochemical features of odorant stimuli strengthens the view that odor preference is partially predetermined. These findings open up new perspectives for the study of the neural mechanisms of hedonic perception.     

The role of lactic acid bacteria in colon cancer prevention: mechanistic considerations

Colorectal cancer is one of the most important causes of cancer morbidity and mortality in Western countries. While a myriad of healthful effects have been attributed to the probiotic lactic acid bacteria, perhaps the most controversial remains that of anticancer activity. It should be pointed out already at this point that there is no direct experimental evidence for cancer suppression in humans as a result of consumption of lactic cultures in fermented or unfermented dairy products. However, there is a wealth of indirect evidence, based largely on laboratory studies, in the literature. The precise mechanisms by which lactic acid bacteria may inhibit colon cancer are presently unknown. However, such mechanisms might include: enhancing the host's immune response; binding and degrading potential carcinogens; quantitative and/or qualitative alterations in the intestinal microflora incriminated in producing putative carcinogen(s) and promoters (e.g. bile acid-degrading bacteria); producing antitumorigenic or antimutagenic compounds in the colon; alteration of the metabolic activities of intestinal microflora; alteration of physicochemical conditions in the colon; effects on physiology of the host. These potential mechanisms are discussed in the present paper.     

Effect of oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] on azoxymethane-induced biochemical changes related to early colon carcinogenesis in male F344 rats

Epidemiologic studies suggest that the consumption of cruciferous vegetables is associated with a reduced risk for several types of cancer including cancer of colon. Experimental studies indicate that dithiolthiones, naturally occurring substances in cruciferous vegetables, possess anticarcinogenic properties. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a substituted dithiolthione, has been tested for its chemopreventive activity. We studied the effect of dietary oltipraz on liver and colonic mucosal enzymes and DNA adducts to evaluate the modulating role of this agent during the early period of azoxymethane (AOM)-induced carcinogenesis. At 6 weeks of age, groups of animals were fed the AIN-76A diet containing 0 and 300 ppm oltipraz. At 8 weeks of age, all of the animals except vehicle-treated animals were administered a subcutaneous injection of AOM (15 mg/kg body wt/week for 2 weeks). Animals intended for vehicle treatment were administered normal saline subcutaneously. Fifteen hours after the second AOM injection, six animals each from control oltipraz diet groups were sacrificed and liver and colonic mucosa from each animal were used for DNA adduct analysis. Animals intended for liver and colonic mucosal glutathione S-transferase, tyrosine specific protein kinase (TPK), and ornithine decarboxylase (ODC) enzyme assays were killed 5 days after the second AOM or saline injection. The results of this study indicated that dietary oltipraz significantly increased liver (P less than 0.001) and colonic mucosal (P greater than 0.05) weights, but had no effect on body weights (P greater than 0.05). In saline-treated animals, feeding of oltipraz significantly increased the cytosolic glutathione S-transferase (P less than 0.001) and ODC (P less than 0.05) activities in the liver and colon when compared with those fed the control diet. Although our unpublished results indicate an inhibitory role of oltipraz when fed during the initiation and postinitiation phases of intestinal carcinogenesis, the increased ODC activity may indicate a possible role of oltipraz in colon tumor promotion. Additional studies are indicated to test the antitumor properties of oltipraz administered during the postinitiation phases. AOM treatment significantly increased the TPK (P less than 0.0001) and ODC (P less than 0.01) activities in the liver and colon of animals fed the control diet. Dietary oltipraz significantly suppressed the AOM-induced TPK (P less than 0.001) activities in liver and colon and ODC (P less than 0.01) activity of colon. Analysis of nucleic acid bases, O6-methylguanine, and 7-methylguanine revealed that dietary oltipraz significantly (P less than 0.05) inhibited the AOM-induced adduct species. These results suggest that dietary oltipraz enhances the colonic and liver glutathione S-transferase activity and reduced the formation of DNA adducts. In addition, dietary oltipraz modulates liver and colonic ODC and TPK activities that have been shown to play a role in tumor promotion.     

Dietary fibre--definition, chemistry and analytical determination

Dietary fibre includes non-starch polysaccharides and lignin that are not digested or absorbed in the human small intestine. It contains a mixture of chemically complex polysaccharides. Lignin is a highly cross-linked complex polymer of phenylpropane units. The plant cell wall is the main source of dietary fibre and its structure is reviewed briefly. The structure of the main dietary fibre polysaccharides is then summarized. The demarcation between starch--the main digestible polysaccharide--and dietary fibre presents some problems due to more or less enzyme resistant starch fractions that occur naturally or are formed with processing. "Resistant starch" formed during baking passes through the small intestine in the rat and, probably, in man and is fermented in the colon. It should therefore also be regarded as dietary fibre. Methods for dietary fibre determination fall into two categories: gravimetric methods, weighing the dietary fibre after removal of other components; component analysis methods, determining monomeric composition of fibre polysaccharides (preferably by gas-liquid chromatography) supplemented with a gravimetric lignin determination and separate assay of uronic acid components (pectin). Recently developed enzymatic gravimetric methods are most convenient for the assay of total dietary fibre or water soluble and insoluble fibre separately, whereas component analysis is required for determining the dietary fibre composition.     

Animal models to study bile acid metabolism

The use of animal models, particularly genetically modified mice, continues to play a critical role in studying the relationship between bile acid metabolism and human liver disease. Over the past 20 years, these studies have been instrumental in elucidating the major pathways responsible for bile acid biosynthesis and enterohepatic cycling, and the molecular mechanisms regulating those pathways. This work also revealed bile acid differences between species, particularly in the composition, physicochemical properties, and signaling potential of the bile acid pool. These species differences may limit the ability to translate findings regarding bile acid-related disease processes from mice to humans. In this review, we focus primarily on mouse models and also briefly discuss dietary or surgical models commonly used to study the basic mechanisms underlying bile acid metabolism. Important phenotypic species differences in bile acid metabolism between mice and humans are highlighted.     

Bacterial antimutagenesis by hydroxycinnamic acids from plant cell walls

We have determined the abilities of (E)-ferulic acid, (E)-p-coumaric acid and (E,E)-5-5-dehydrodiferulic acid to protect against different types of mutation in a simple bacterial model. These antimutagenic properties were compared with those of the related compound curcumin, and also with those of an extract containing hydroxycinnamic acids obtained by the saponification of the cell walls of wheat coleoptiles. Three known mutagens, bleomycin, hydrogen peroxide and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were used to chemically induce reversion mutation, while the known antimutagen Trolox was used as a positive control. Both the pure hydroxycinnamic acids and the extract from the cell walls showed antimutagenic properties. It is known that hydroxycinnamic acids ester-linked to plant cell walls can be released in the human colon by the action of microbial esterases. Providing the current data extrapolate to mammalian cells, they suggest that antimutagenic properties of hydroxycinnamic acids released from plant cell walls could play a role in dietary fibre protection against cancer.     

Role of extracellular matrix components in the formation of biofilms and their contribution to the biocontrol activity of Pseudomonas chlororaphis PCL1606

Pseudomonas chlororaphis PCL1606 (PcPCL1606) displays plant-colonizing features and exhibits antagonistic traits against soil-borne phytopathogenic fungi. Biofilm formation could be relevant for the PcPCL1606 lifestyle, and in this study the role of some putative extracellular matrix components (EMC; Fap-like fibre, alginate and Psl-like polysaccharides) in the biofilm architecture and biocontrol activity of this bacterium were determined. EMC such as the Fap-like fibre and alginate polysaccharide play secondary roles in biofilm formation in PcPCL1606, because they are not fundamental to its biofilm architecture in flow cell chamber, but synergistically they have shown to favour bacterial competition during biofilm formation. Conversely, studies on Psl-like polysaccharide have revealed that it may contain mannose, and that it is strongly involved in the PcPCL1606 biofilm architecture and niche competition. Furthermore, the Fap-like fibre and Psl-like exopolysaccharide play roles in early surface attachment and contribute to biocontrol activity against the white root rot disease caused by Rosellinia necatrix in avocado plants. These results constitute the first report regarding the study of the extracellular matrix of the PcPCL1606 strain and highlight the importance of a putative Fap-like fibre and Psl-like exopolysaccharide produced by PcPCL1606 in the biofilm formation process and interactions with the host plant root.     

Different Degrees of Plant Invasion Significantly Affect the Richness of the Soil Fungal Community

Several studies have shown that soil microorganisms play a key role in the success of plant invasion. Thus, ecologists have become increasingly interested in understanding the ecological effects of biological invasion on soil microbial communities given continuing increase in the effects of invasive plants on native ecosystems. This paper aims to provide a relatively complete depiction of the characteristics of soil microbial communities under different degrees of plant invasion. Rhizospheric soils of the notorious invasive plant Wedelia trilobata with different degrees of invasion (uninvaded, low-degree, and high-degree using its coverage in the invaded ecosystems) were collected from five discrete areas in Hainan Province, P. R. China. Soil physicochemical properties and community structure of soil microorganisms were assessed. Low degrees of W. trilobata invasion significantly increased soil pH values whereas high degrees of invasion did not significantly affected soil pH values. Moreover, the degree of W. trilobata invasion exerted significant effects on soil Ca concentration but did not significantly change other indices of soil physicochemical properties. Low and high degrees of W. trilobata invasion increased the richness of the soil fungal community but did not pose obvious effects on the soil bacterial community. W. trilobata invasion also exerted obvious effects on the community structure of soil microorganisms that take part in soil nitrogen cycling. These changes in soil physicochemical properties and community structure of soil microbial communities mediated by different degrees of W. trilobata invasion may present significant functions in further facilitating the invasion process.     

Plant biodiversity: phytochemicals and health

Biodiversity may be defined as the variability occuring among living organisms and affecting all species of animals and plants, their genetics and their environment. Biological diversity of plants also relies on the chemical diversity deriving from their specialized metabolites which possess a wide range of different chemical structures as a result of plant evolution. They are responsible for the plant ecological properties and are required for the plant-environment interactions. In addition, many of them display important pharmacological properties. In the recent years, the growing interest in using plant metabolites to treat diseases in humans and animals and the high request of health products originating from natural sources rather than synthetic has revived the research on plant biodiversity to identify new bioactive molecules. Based on our studies on the chemical and biological characterization of rare or less studied plant species, the present paper aims to describe a selection of botanical species with phytopharmaceutical importance in order to highlight the chemical polymorphism deriving from their biodiversity along with its implications on bioactivity.     

Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats

Inhaled fibres with certain physico-chemical properties are known to induce mesothelioma in humans. The induction of reactive oxygen (ROS) or nitrogen species (RNS) have been suggested as molecular mechanism of fibre induced carcinogenesis. In earlier studies we were able to demonstrate that crocidolite asbestos in vivo induces mutations in transgenic rats with a specific molecular spectrum that indicates the involvement of 8-hydroxydeoxyguanosine (8-OHdG) as pre-mutagenic adduct. 8-OHdG may be induced by primary (direct) and/or secondary (cellular mediated) mechanisms. Therefore, the induction of 8-OHdG as well as the inflammatory response of animals treated with fibre samples significantly differing in their physico-chemical characteristics was investigated. As appropriate system to study mesothelioma carcinogenesis, intraperitoneal injection in rats was used with samples of UICC crocidolite, crocidolite with reduced iron content, and a vitreous fibre (MMVF 11). Equal numbers of carcinogenic fibres from each sample revealed significant comparable increases in 8-OHdG induction. Parameters of inflammation (percentage of macrophages and TNF-alpha secretion) correlated significantly with the induction of 8-OHdG, 10 weeks after treatment.     

Mechano-electric feedback and atrial fibrillation

Atrial fibrillation frequently occurs under conditions associated with atrial dilatation suggesting a role of mechano-electric feedback in atrial arrhythmogenesis. Although atrial arrhythmias may be due both to abnormal focal activity and reentrant mechanisms, the majority of sustained atrial arrhythmias have been ascribed to reentrant activity. Atrial stretch may contribute to focal arrhythmias by inducing afterdepolarizations and to reentrant arrhythmias by increasing the atrial surface, by shortening the refractory period and/or slowing the conduction velocity and by increasing their spatial dispersion. Experimental and clinical studies have demonstrated that changes in mechanical loading conditions may modulate the electrophysiological properties of the atria. These studies have, for the most part, involved the effects of acute stretch on atrial refractoriness. While studies in humans and intact animals yield divergent results due to the variety of loading conditions and neurohumoral influences, experimental studies in isolated preparations clearly show that atrial refractory period and action potential duration at early levels of repolarization shorten by acute atrial dilatation. Both experimental and human studies have shown that acute atrial stretch is arrhythmogenic and may induce triggered premature beats and atrial fibrillation.     

AdipoRon Attenuates Wnt Signaling by Reducing Cholesterol-Dependent Plasma Membrane Rigidity

The increasing prevalence of adult and adolescent obesity and its associated risk of colorectal cancer reinforces the urgent need to elucidate the underlying mechanisms contributing to the promotion of colon cancer in obese individuals. Adiponectin is an adipose tissue-derived adipokine, whose levels are reduced during obesity. Both epidemiological and preclinical data indicate that adiponectin suppresses colon tumorigenesis. We have previously demonstrated that both adiponectin and AdipoRon, a small-molecule adiponectin receptor agonist, suppress colon cancer risk in part by reducing the number of Lgr5⁺ stem cells in mouse colonic organoids. However, the mechanism by which the adiponectin signaling pathway attenuates colon cancer risk remains to be addressed. Here, we have hypothesized that adiponectin signaling supports colonic stem cell maintenance through modulation of the biophysical properties of the plasma membrane (PM). Specifically, we investigated the effects of adiponectin receptor activation by AdipoRon on the biophysical perturbations linked to the attenuation of Wnt-driven signaling and cell proliferation as determined by LEF luciferase reporter assay and colonic organoid proliferation, respectively. Using physicochemical sensitive dyes, Di-4-ANEPPDHQ and C-laurdan, we demonstrated that AdipoRon decreased the rigidity of the colonic cell PM. The decrease in membrane rigidity was associated with a reduction in PM free cholesterol levels and the intracellular accumulation of free cholesterol in lysosomes. These results suggest that adiponectin signaling plays a role in modulating cellular cholesterol homeostasis, PM biophysical properties, and Wnt-driven signaling. These findings are noteworthy because they may in part explain how obesity drives colon cancer progression.     

加拿大一枝黄花入侵对土壤动物群落结构的影响

外来植物对入侵地土壤动物群落及理化性质影响的研究不仅有助于评估入侵植物对生态系统的影响,而且对探索外来植物入侵的土壤动物学响应机制尤为重要。为了了解加拿大一枝黄花对入侵地土壤动物的群落结构及理化性质的影响,本文分季节分层次对加拿大一枝黄花不同程度的入侵地进行取样,获得土壤动物9900个,隶属3门11纲14目,弹尾目和蜱螨类均为优势类群。入侵程度不同的样地中土壤动物个体数量和类群组成不同。土壤动物个体数量和类群数量表现为轻度入侵区＞中度入侵区＞重度入侵区;多样性指数和均匀性指数表现为轻度入侵区＜中度入侵区＜重度入侵区,优势度指数表现与前两指数相反。加拿大一枝黄花的入侵没有改变土壤动物表聚性特点。非度量多维标度排序分析表明,不同入侵程度下的土壤动物分为3类,即轻度入侵类、中度入侵类、重度入侵类。不同入侵区域土壤的pH、有机质含量、铵态氮、速效钾和速效磷差异显著(P＜0.05),土壤的含水量和温度差异不显著(P＞0.05)。灰色关联分析表明,入侵区域土壤铵态氮对土壤动物关联最大,有机质含量次之,再次是速效磷和pH,土壤含水量的影响最小。因而,加拿大一枝黄花的入侵,改变了入侵地土壤理化性质(尤其是对铵态氮的调控),进而改变了土壤动物的群落结构,创造了利于自身生长、竞争有利的土壤环境。     

5-hydroxytryptamine and vascular disease

The release of 5-hydroxytryptamine (5-HT) from aggregating platelets may trigger acute vasospastic episodes of larger arteries, which can lead to tissue ischemia, particularly in the coronary and cerebral circulations. In hypertensive humans and animals, 5-HT may play a role in the maintenance of the chronic increase in peripheral resistance. This is suggested by the observations that 1) in several models of chronic hypertension there is a specific increase in the responsiveness of the blood vessel wall to the vasoconstrictor properties of 5-HT and a delayed tachyphylaxis to the monoamine; 2) the ability of hypertensive animals to clear 5-HT from the blood is reduced, and the platelets of hypertensive patients take up less 5-HT than those of normotensive humans; their activation to release 5-HT is accelerated; and 3) ketanserin, a 5-HT2-serotonergic antagonist devoid of agonistic properties, lowers arterial blood pressure in hypertensive humans and animals.     

Prebiotics and lipid metabolism.

Prebiotics are defined as nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth or the activity of one or a limited number of bacteria (bifidobacteria, lactobacilli) in the colon. Dietary fructans are nutritionally interesting oligosaccharides that strictly conform to the definition of prebiotics and (in view of experimental studies in animals and of less numerous studies in humans) exhibit interesting serum or hepatic lipid lowering properties. Other nondigestible/fermentable nutrients, which also modulate intestinal flora activity, exhibit cholesterol or triglyceride lowering effects. Are changes in intestinal bacterial flora composition or fermentation activity responsible for those effects? What is the future of prebiotics in the nutritional control of lipidaemia and cardiovascular disease risk in humans? Those questions only receive partial response in the present review because studies of the systemic effects of prebiotics are still in their infancy, and require fundamental research devoted to elucidating the biochemical and physiological events that allow prebiotics to exert systemic effects on lipid metabolism.     

Prevention of Cancer-by Agents that Suppress Oxygen Radical Formation

The prevention of cancer by agents in our diet has led to the concept that oxygen radicals are a necessary component of a variety of human cancers including breast, colon and prostatic cancer. These cancers are putatively promoted by estradiol, bile acids and androgens. Epidemiological studies have shown that these cancers are suppressed in vegetarian populations. Vegetable components that may be responsible for this cancer prevention are Vitamin A, retinoids and protease inhibitors (PIS). These agents have been shown to suppress the formation of hydrogen peroxide in promoter-induced neutrophils. They also have been shown to block two-stage carcinogenesis and breast cancer when fed to animals. PIS also suppress experimentally-induced colon cancer and spontaneous liver cancer. Moreover, a new series of cancer-preventive agents, Sarcophytols (isolated by Fujiki and co-workers), are capable of suppressing two-stage carcinogenesis, breast and colon cancers in rodents when given in low concentrations. Sarcophytols were also active suppressors of H₂O₂ formation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced neutrophils. These observations point to an essential role of oxygen radicals in carcinogenesis. Suppression of the oxygen radical response of neutrophils in relation to cancer preventive agents is a facile assay of these important substances. The mechanism of action of oxygen radicals in promoting carcinogenesis is a multiple one. including: (1) activation of oncogenes, (2) modification of DNA bases, and (3) formation of single-strand breaks leading to poly(ADP)ribose polymerase activation.